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Increased plant sterol and stanol levels in brain of Watanabe rabbits fed rapeseed oil derived plant sterol or stanol esters.
Foods containing plant sterol or stanol esters can be beneficial in lowering LDL-cholesterol concentration, a major risk factor for CVD. The present study examined whether high dietary intake of rapeseed oil (RSO) derived plant sterol and stanol esters is associated with increased levels of these components in brain tissue of homozygous and heterozygous Watanabe rabbits, an animal model for familial hypercholesterolemia. Homozygous animals received either a standard diet, RSO stanol or RSO sterol ester while heterozygous animals were additionally fed with 2 g cholesterol/kg to the respective diet form for 120 d (n 9 for each group). Concentrations of cholesterol, its precursor lathosterol, plant sterols and stanols in brain and additionally in liver and plasma were determined by highly sensitive GC-MS. High-dose intake of RSO derived plant sterols and stanols resulted in increased levels of these components in plasma and liver. In brain a limited uptake of plant sterols and stanols was proven, indicating that these compounds passed the blood-brain barrier and may be retained in the brain tissue of Watanabe rabbits. Plant stanol ester feeding lowered plant sterol levels in brain, liver, and plasma. Cholesterol synthesis in brain, indicated by lathosterol, a local surrogate cholesterol synthesis marker, does not seem to be affected by plant sterol or stanol ester feeding. We conclude that high dose intake of plant sterol and stanol esters in Watanabe rabbits results in elevated concentrations of these components not only in the periphery but also in the central nervous system. PMID:17537294
Fricke, Christiane B; Schrřder, Malene; Poulsen, Morten; von Bergmann, Klaus; Wester, Ingmar; Knudsen, Ib; Mortensen, Alicja; Lütjohann, Dieter
The expanding market of 'functional foods' containing plant sterols and stanols has focused interest on their cholesterol-lowering effects as well on possible adverse effects. Trials of cholesterol lowering demonstrate that intake of 2 g\\/day of plant sterols and stanols reduces serum low-density lipoprotein (LDL) cholesterol concentrations by approximately 10%. Safety concerns regarding elevations in serum plant sterol levels, or effects
M. J. Tikkanen
Cerebral accumulation of dietary derivable plant sterols does not interfere with memory and anxiety related behavior in Abcg5-/- mice.
Plant sterols such as sitosterol and campesterol are frequently applied as functional food in the prevention of atherosclerosis. Recently, it became clear that plasma derived plant sterols accumulate in murine brains. We questioned whether plant sterols in the brain are associated with alterations in brain cholesterol homeostasis and subsequently with brain functions. ATP binding cassette (Abc)g5-/- mice, a phytosterolemia model, were compared to Abcg5+/+ mice for serum and brain plant sterol accumulation and behavioral and cognitive performance. Serum and brain plant sterol concentrations were respectively 35-70-fold and 5-12-fold increased in Abcg5-/- mice (P<0.001). Plant sterol accumulation resulted in decreased levels of desmosterol (P<0.01) and 24(S)-hydroxycholesterol (P<0.01) in the hippocampus, the brain region important for learning and memory functions, and increased lanosterol levels (P<0.01) in the cortex. However, Abcg5-/- and Abcg5+/+ displayed no differences in memory functions or in anxiety and mood related behavior. The swimming speed of the Abcg5-/- mice was slightly higher compared to Abcg5+/+ mice (P<0.001). In conclusion, plant sterols in the brains of Abcg5-/- mice did have consequences for brain cholesterol metabolism, but did not lead to an overt phenotype of memory or anxiety related behavior. Thus, our data provide no contra-indication for nutritional intake of plant sterol enriched nutrition. PMID:21431910
Vanmierlo, Tim; Rutten, Kris; van Vark-van der Zee, Leonie C; Friedrichs, Silvia; Bloks, Vincent W; Blokland, Arjan; Ramaekers, Frans C; Sijbrands, Eric; Steinbusch, Harry; Prickaerts, Jos; Kuipers, Folkert; Lütjohann, Dieter; Mulder, Monique
The expanding market of 'functional foods' containing plant sterols and stanols has focused interest on their cholesterol-lowering effects as well on possible adverse effects. Trials of cholesterol lowering demonstrate that intake of 2 g/day of plant sterols and stanols reduces serum low-density lipoprotein (LDL) cholesterol concentrations by approximately 10%. Safety concerns regarding elevations in serum plant sterol levels, or effects on fat-soluble vitamin absorption or hypothetical effects on serum sex hormone balance have received attention and been addressed in studies. Plant sterol (but not stanol) supplementation increased serum plant sterol concentrations but these levels remained much lower than those observed in homozygous sitosterolemia making an adverse health effect unlikely. Prolonged statin therapy also causes elevations in all cholesterol-adjusted plant sterol levels as well as small but significant elevations in serum unadjusted campesterol levels from baseline. This is probably caused by a statin-induced reduction in biliary cholesterol efflux resulting in a diminished intestinal cholesterol pool. The diminished competition with cholesterol molecules allows more plant sterol molecules to become incorporated in mixed micelles facilitating their uptake in enterocytes. With the exception of beta-carotene, reductions in serum concentrations of fat-soluble (pro)vitamins are usually abolished by adjustment for cholesterol suggesting that they reflect reductions in carrier lipoproteins, mainly LDL. The small reductions in serum beta-carotene are not regarded as a major concern, nor have any adverse effects on sex hormone metabolism been demonstrated apart from parenteral administration of large doses in experimental animals. However, as increasing consumer populations become exposed to a large variety of food products enriched with plant sterols and stanols the likelihood of rare adverse effects increases and surveillance is necessary. PMID:16596801
Tikkanen, M J
Pharmacological properties of plant sterols
Plant sterols have been investigated as one of the safe potential alternative methods in lowering plasma cholesterol levels. Several human studies have shown that plant sterols\\/stanols significantly reduce plasma total and LDL cholesterol. In this article, pharmacological characteristics of plant sterols\\/stanols have been summarized and discussed. In particular, experimental data that demonstrate the effects of dietary phytosterols on lipid metabolism
Mohammed H. Moghadasian
Recent progress in the biochemistry of plant steroids other than sterols (Saponins, glycoalkaloids, pregnane derivatives, cardiac glycosides, and sex hormones)
Recent studies concerning the biosynthesis, metabolism, and possible functions of steroids other than sterols in plants are\\u000a reviewed and discussed. These studies embrace the saponins, glycoalkaloids, pregnane derivatives, cardiac glycosides, as well\\u000a as their aglycones, and the sex hormones.
Erich Heftmann
Serum Plant Sterol Concentration but Not the Cholesterol Precursor Sterol Concentrations in Young Children (The STRIP Study)1
Plant sterol supplementation reduces serum cholesterol concentration but may increase serum plant ste- rol concentrations, especially in children. We determined whether natural dietary plant sterols derived mainly from veg- etable oil or margarine in early childhood affect serum con- centrations of plant sterols (campesterol and sitosterol) and cholesterol precursor sterols (D-8 cholestenol, desmosterol, and lathosterol), reflecting endogenous cholesterol synthesis. We
Anne Tammi; Tapani Ronnemaa; Liisa Valsta; Ritva Seppanen; Leena Rask-Nissila; Tatu A. Miettinen; Helena Gylling; Jorma Viikari; Meri Anttolainen; Olli Simell
Plant Sterols in Cereals and Cereal Products
Cereal Chem. 79(1):148-154 The total plant sterol contents (free sterols and covalently bound structures) of the main cereals cultivated in Finland were determined. Furthermore, sterol contents were determined for different flour and bran fractions in the milling process of wheat and rye, as well as plant sterol contents in various milling and retail bakery products. The sample prep- aration procedure
V. Piironen; J. Toivo; A.-M. Lampi
Cholesterol-lowering effect of plant sterols.
Plant sterols are plant components that have a chemical structure similar to cholesterol except for the addition of an extra methyl or ethyl group; however, plant sterol absorption in humans is considerably less than that of cholesterol. In fact, plant sterols reduce cholesterol absorption and thus reduce circulating levels of cholesterol. Earlier studies that have tested the efficacy of plant sterols as cholesterol-lowering agents incorporated plant sterols into fat spreads. Later on, plant sterols were added to other food matrices, including juices, nonfat beverages, milk and yogurt, cheese, meat, croissants and muffins, and cereal and chocolate bars. The beneficial physiologic effects of plant sterols could be further enhanced by combining them with other beneficial substances, such as olive and fish oils, fibers, and soy proteins, or with exercise. The addition of plant sterols to the diet is suggested by health experts as a safe and effective way to reduce the risk of coronary heart disease. PMID:18937893
AbuMweis, Suhad S; Jones, Peter J H
Cholesterol-lowering action of plant sterols
Plant sterols have an extended history of use as cholesterol-lowering agents. Until the 1970s, the principal interest in plant\\u000a sterols lay in effects of sitosterol, but over the past decade interest has reemerged in using plant sterols in functional\\u000a foods. Hydrogenated plant sterols have been shown efficacious in lowering lipid levels, inhibiting cholesterol absorption\\u000a and regressing plaque in animals. Hydrogenated
Peter J. H. Jones
Cholesterol-lowering effect of plant sterols
Plant sterols are plant components that have a chemical structure similar to cholesterol except for the addition of an extra\\u000a methyl or ethyl group; however, plant sterol absorption in humans is considerably less than that of cholesterol. In fact,\\u000a plant sterols reduce cholesterol absorption and thus reduce circulating levels of cholesterol. Earlier studies that have tested\\u000a the efficacy of plant
Suhad S. AbuMweis; Peter J. H. Jones
Dietary intake of plant sterols stably increases plant sterol levels in the murine brain.
Plant sterols such as sitosterol and campesterol are frequently administered as cholesterol-lowering supplements in food. Recently, it has been shown in mice that, in contrast to the structurally related cholesterol, circulating plant sterols can enter the brain. We questioned whether the accumulation of plant sterols in murine brain is reversible. After being fed a plant sterol ester-enriched diet for 6 weeks, C57BL/6NCrl mice displayed significantly increased concentrations of plant sterols in serum, liver, and brain by 2- to 3-fold. Blocking intestinal sterol uptake for the next 6 months while feeding the mice with a plant stanol ester-enriched diet resulted in strongly decreased plant sterol levels in serum and liver, without affecting brain plant sterol levels. Relative to plasma concentrations, brain levels of campesterol were higher than sitosterol, suggesting that campesterol traverses the blood-brain barrier more efficiently. In vitro experiments with brain endothelial cell cultures showed that campesterol crossed the blood-brain barrier more efficiently than sitosterol. We conclude that, over a 6-month period, plant sterol accumulation in murine brain is virtually irreversible. PMID:22279184
Vanmierlo, Tim; Weingärtner, Oliver; van der Pol, Susanne; Husche, Constanze; Kerksiek, Anja; Friedrichs, Silvia; Sijbrands, Eric; Steinbusch, Harry; Grimm, Marcus; Hartmann, Tobias; Laufs, Ulrich; Böhm, Michael; de Vries, Helga E; Mulder, Monique; Lütjohann, Dieter
Distribution of free and glycosylated sterols within Cycas micronesica plants
Flour derived from Cycas micronesica seeds was once the dominant source of starch for Guam's residents. Cycad consumption has been linked to high incidence of human neurodegenerative diseases. We determined the distribution of the sterols stigmasterol and ?-sitosterol and their derived glucosides stigmasterol ?-d-glucoside and ?-sitosterol ?-d-glucoside among various plant parts because they have been identified in cycad flour and
Thomas E. Marler; Christopher A. Shaw
Effect of rapeseed oil-derived plant sterol and stanol esters on atherosclerosis parameters in cholesterol-challenged heterozygous Watanabe heritable hyperlipidaemic rabbits.
Rapeseed oil (RSO) is a novel source of plant sterols, containing the unique brassicasterol in concentrations higher than allowed for plant sterol blends in food products in the European Union. Effects of RSO sterols and stanols on aortic atherosclerosis were studied in cholesterol-fed heterozygous Watanabe heritable hyperlipidaemic (Hh-WHHL) rabbits. Four groups (n 18 per group) received a cholesterol-added (2 g/kg) standard chow or this diet with added RSO stanol esters (17 g/kg), RSO stanol esters (34 g/kg) or RSO sterol esters (34 g/kg) for 18 weeks. Feeding RSO stanol esters increased plasma campestanol (P < 0.001) and sitostanol (P < 0.001) and aortic campestanol (P < 0.05) compared with controls. Feeding RSO sterol esters increased concentrations of plasma campesterol (P < 0.001), sitosterol (P < 0.001) and brassicasterol (P < 0.001) and aortic campesterol (P < 0.01). Significantly lower plasma cholesterol (P < 0.001) was recorded in the treated groups after 3 weeks and throughout the study. LDL-cholesterol was reduced 50 % in the high-dose RSO sterol ester (P < 0.01) and high-dose RSO stanol ester (P < 0.001) groups compared with controls. Atherosclerotic lesions were found in three rabbits in each of the RSO stanol ester groups and in one in the RSO sterol ester group. Aortic cholesterol was decreased in the treated groups (P < 0.001) in response to lowering of plasma cholesterol induced by RSO sterol and stanol esters. In conclusion, RSO stanol and sterol esters with a high concentration of brassicasterol were well tolerated. They were hypocholesterolaemic and inhibited experimental atherosclerosis in cholesterol-fed Hh-WHHL rabbits. A significant uptake of plant sterols into the blood and incorporation of campesterol and campestanol into aortic tissue was recorded. PMID:19772679
Schrřder, Malene; Fricke, Christiane; Pilegaard, Kirsten; Poulsen, Morten; Wester, Ingmar; Lütjohann, Dieter; Mortensen, Alicja
[The effects of plant sterols on hypercholesterolemia].
Increased serum total and LDL-cholesterol concentrations are major risk factors for cardiovascular diseases. Many clinical trials have proven that plant sterol and stanol esters can effectively decrease high serum total and LDL cholesterol. They reduce the intestinal absorption of cholesterol by decreasing the incorporation of dietary and biliary cholesterol into micelles displacing cholesterol from these micelles. They also increase LDL receptor activity on liver cells causing a higher uptake of LDL cholesterol and thus decreasing the serum LDL cholesterol concentration. Animal studies have indicated that plant sterols and stanols may also lower atherosclerotic lesions development. However, the evidence from human studies to confirm this is still lacking. Anyhow, plant sterol and stanol esters can be considered as an effective and safe cholesterol-lowering functional food ingredient. To achieve additional effects they can be combined with statin therapy, and this combination is also well tolerated and safe. PMID:18198627
Reiner, Zeljko; Tedeschi-Reiner, Eugenia
Electrochemical synthesis of glycoconjugates from activated sterol derivatives.
Several derivatives of cholesterol and other 3?-hydroxy-?(5)-steroids were prepared and tested as sterol donors in electrochemical reactions with sugar alcohols. The reactions afforded glycoconjugates with sugar linked to a steroid moiety by an ether bond. Readily available sterol diphenylphosphates yielding up to 54% of the desired glycoconjugate were found to be the best sterol donors. PMID:24486463
Tomkiel, Aneta M; Kowalski, Jan; P?oszy?ska, Jolanta; Siergiejczyk, Leszek; Lotowski, Zenon; Sobkowiak, Andrzej; Morzycki, Jacek W
A Reappraisal of the Mechanism by Which Plant Sterols Promote Neutral Sterol Loss in Mice
Dietary plant sterols (PS) reduce serum total and LDL-cholesterol in hyperlipidemic animal models and in humans. This hypocholesterolemic effect is generally ascribed to inhibition of cholesterol absorption. However, whether this effect fully explains the reported strong induction of neutral sterol excretion upon plant sterol feeding is not known. Recent data demonstrate that the intestine directly mediates plasma cholesterol excretion into feces, i.e., without involvement of the hepato-biliary route. Objective Aim of this study was to determine whether stimulation of fecal neutral sterol loss during PS feeding is (partly) explained by increased intestinal cholesterol excretion and to assess the role of the cholesterol transporter Abcg5/Abcg8 herein. Methods and Results Wild-type mice were fed a control diet or diets enriched with increasing amounts of PS (1%, 2%, 4% or 8%, wt/wt) for two weeks. In addition, Abcg5-/- mice were fed either control or 8% PS diet. PS feeding resulted in a dose-dependent decrease of fractional cholesterol absorption (?2–7-fold reduction) in wild-type mice and ?80% reduction in Abcg5-/- mice. Furthermore, PS feeding led to a strong, dose-independent induction of neutral sterol excretion (3.4-fold in wild-types and 2.7-fold in Abcg5-/- mice) without changes in biliary cholesterol secretion. It was calculated that PS feeding stimulated intestinal cholesterol excretion by ?500% in wild-type mice and by ?250% in Abcg5-/-. Conclusions Our data indicate that in mice the cholesterol-lowering effects of PS are to a large extent attributable to stimulation of intestinal, non-bile derived, cholesterol excretion. The Abcg5/Abcg8 heterodimer is involved in facilitating this PS-induced flux of cholesterol.
Brufau, Gemma; Kuipers, Folkert; Lin, Yuguang; Trautwein, Elke A.; Groen, Albert K.
Glycerol derivatives and sterols from Sargassum parvivesiculosum.
Five glycerol derivatives (1-5) and three sterols (6-8) were isolated from the EtOH extraction of the brown alga of Sargassum parvivesiculosum. On the basis of spectroscopic methods, their structures were elucidated as 1,3-di-O-[2',2'-di-(p-phenylene) isopropylidene] glycerol (1), (2S)-1-O-heptatriacontanoyl glycerol (2), (2S)-1,2-di-O-palmitoyl-3-O-(6-sulpho-alpha-D-quinovopyranosyl) glycerol (3), (2S)-1-O-palmitoyl glycerol (4), (2S)-1,3-di-(O-palmitoyl)-2-O-octadecanoyl glycerol (5), 24-ethylcholest-5,23Z-dien-3beta,28zeta-diol (6), 24-vinylcholest-5-en-24zeta-hydroperoxy (7), 24-ethylcholest-4,24(28)-dien-3beta-ol (8), respectively. Among them, 1 and 2 were new. PMID:15304997
Qi, Shu-Hua; Zhang, Si; Huang, Jian-She; Xiao, Zhi-Hui; Wu, Jun; Long, Li-Juan
Plant sterols and stanols: Their role in health and disease
Mammalian physiological processes, and likely any organism with a biliary tree, can distinguish between dietary cholesterol and noncholesterols, retaining very little of the noncholesterol in their bodies. Historically, the distinction between plant sterols and cholesterol has been known about for more than a century. That plants sterols are not "absorbed" has been investigated for almost half a century. The ingestion
Shailendra B. Patel
Effect of struture and form on the ability of plant sterols to inhibit cholesterol absorption in hamsters
We investigated the effect of three types of plant sterols (4-desmethylsterols, 4,4?-dimethylsterols, and pentacyclic triterpene\\u000a alcohols) in three forms (free, esterified with FA, or with phenolic acids) on cholesterol absorption. Plant sterol fractions\\u000a derived from soybean (99% 4-desmethylsterols), rice bran (70% 4,4?-dimethylsterols), or shea nut (89% pentacyclic triterpene\\u000a alcohols) were fed to male hamsters (n=20\\/group) as free sterols or esterified
Gert W. Meijer; Marco A. J. J. Bressers; W. Arjan de Groot; Mike Rudrum
Plant sterols and stanols: their role in health and disease.
Mammalian physiological processes, and likely any organism with a biliary tree, can distinguish between dietary cholesterol and non-cholesterols, retaining very little of the non-cholesterol in their bodies. Historically, the distinction between plant sterols and cholesterol has been known about for a century or more. That plants sterols were not 'absorbed' has been investigated for almost half a century. Indeed, the oral of plant sterols in gram quantities was shown to interfere with cholesterol absorption and is one of the oldest pharmacological therapies for hypercholesterolemia. Although the basis for the latter was shown to be caused by exclusion of cholesterol from intestinal micelles by plant sterols, it was not until the identification of the a rare genetic disease, sitosterolemia, first described in 1974, that led to the hypothesis that specific molecular mechanism(s) governed both the entry and excretion of sterols by the body. This talk will cover the physiology of dietary sterol metabolism, genetics and pathophysiology of sitosterolemia. Additionally, the role of plant sterols in normal and abnormal metabolism in humans as well as selected animal models will be discussed. PMID:19343077
Patel, Shailendra B
STEROL METHYLTRANSFERASE 1 Controls the Level of Cholesterol in Plants
The side chain in plant sterols can have either a methyl or ethyl addition at carbon 24 that is absent in cholesterol. The ethyl addition is the product of two sequential methyl additions. Arabidopsis contains three genes—sterol methyltransferase 1 (SMT1), SMT2, and SMT3—homologous to yeast ERG6, which is known to encode an S-adenosylmethionine–dependent C-24 SMT that catalyzes a single methyl addition. The SMT1 polypeptide is the most similar of these Arabidopsis homologs to yeast Erg6p. Moreover, expression of Arabidopsis SMT1 in erg6 restores SMT activity to the yeast mutant. The smt1 plants have pleiotropic defects: poor growth and fertility, sensitivity of the root to calcium, and a loss of proper embryo morphogenesis. smt1 has an altered sterol content: it accumulates cholesterol and has less C-24 alkylated sterols content. Escherichia coli extracts, obtained from a strain expressing the Arabidopsis SMT1 protein, can perform both the methyl and ethyl additions to appropriate sterol substrates, although with different kinetics. The fact that smt1 null mutants still produce alkylated sterols and that SMT1 can catalyze both alkylation steps shows that there is considerable overlap in the substrate specificity of enzymes in sterol biosynthesis. The availability of the SMT1 gene and mutant should permit the manipulation of phytosterol composition, which will help elucidate the role of sterols in animal nutrition.
Diener, Andrew C.; Li, Haoxia; Zhou, Wen-xu; Whoriskey, Wendy J.; Nes, W. David; Fink, Gerald R.
Reminiscences of research on the chemistry and biology of natural sterols in insects, plants and humans.
Natural sterols often occur as a heterogeneous mixture of homologs, which had disturbed the progress of steroid research. Development and application of GC methodology overcame this difficulty and enabled us to obtain detailed sterol profiles. Together, fine synthesis of stereo-defined isomers and homologs of steroids having oxygenated side chains allowed us to compare them with natural samples as well as to investigate structure-activity relationship. Advance of HPLC technology also facilitated the determination of the stereochemical structure of naturally occurring steroidal compounds, which were obtained only in minute amounts. This review highlights three topics out of our steroid research that have been performed mainly at Tokyo Institute of Technology around 1970-1990. These are sterol metabolism in insects focusing on the mechanism of the conversion of plant sterols to cholesterol and ecdysone biosynthesis, the synthesis and biochemical research of active forms of vitamin D3 derivatives, and the synthesis and microanalysis of plant hormone brassinosteroids. PMID:24126284
Ikekawa, Nobuo; Fujimoto, Yoshinori; Ishiguro, Masaji
Plant sterols cause macrothrombocytopenia in a mouse model of sitosterolemia.
Mutations in either ABCG5 or ABCG8 cause sitosterolemia, an inborn error of metabolism characterized by high plasma plant sterol concentrations. Recently, macrothrombocytopenia was described in a number of sitosterolemia patients, linking hematological dysfunction to disturbed sterol metabolism. Here, we demonstrate that macrothrombocytopenia is an intrinsic feature of murine sitosterolemia. Abcg5-deficient (Abcg5(-/-)) mice showed a 68% reduction in platelet count, and platelets were enlarged compared with wild-type controls. Macrothrombocytopenia was not due to decreased numbers of megakaryocytes or their progenitors, but defective megakaryocyte development with deterioration of the demarcation membrane system was evident. Lethally irradiated wild-type mice transplanted with bone marrow from Abcg5(-/-) mice displayed normal platelets, whereas Abcg5(-/-) mice transplanted with wild-type bone marrow still showed macrothrombocytopenia. Treatment with the sterol absorption inhibitor ezetimibe rapidly reversed macrothrombocytopenia in Abcg5(-/-) mice concomitant with a strong decrease in plasma plant sterols. Thus, accumulation of plant sterols is responsible for development of macrothrombocytopenia in sitosterolemia, and blocking intestinal plant sterol absorption provides an effective means of treatment. PMID:18156627
Kruit, Janine K; Drayer, A Lyndsay; Bloks, Vincent W; Blom, Nel; Olthof, Sandra G; Sauer, Pieter J J; de Haan, Gerald; Kema, Ido P; Vellenga, Edo; Kuipers, Folkert
Cellular sterol ester synthesis in plants is performed by an enzyme (phospholipid:sterol acyltransferase) different from the yeast and mammalian acyl-CoA:sterol acyltransferases.
A gene encoding a sterol ester-synthesizing enzyme was identified in Arabidopsis. The cDNA of the Arabidopsis gene At1g04010 (AtPSAT) was overexpressed in Arabidopsis behind the cauliflower mosaic virus 35S promoter. Microsomal membranes from the leaves of overexpresser lines catalyzed the transacylation of acyl groups from phosphatidylethanolamine to sterols. This activity correlated with the expression level of the AtPSAT gene, thus demonstrating that this gene encodes a phospholipid:sterol acyltransferase (PSAT). Properties of the AtPSAT were examined in microsomal fractions from the tissues of an overexpresser. The enzyme did not utilize neutral lipids, had the highest activity with phosphatidylethanolamine, had a 5-fold preference for the sn-2 position, and utilized both saturated and unsaturated fatty acids. Various sterols and sterol intermediates, including triterpenic precursors, were acylated by the PSAT, whereas other triterpenes were not. Sterol selectivity studies showed that the enzyme is activated by end product sterols and that sterol intermediates are preferentially acylated by the activated enzyme. This indicates that PSAT both regulates the pool of free sterols as well as limits the amount of free sterol intermediates in the membranes. Two T-DNA insertion mutants in the AtPSAT gene, with strongly reduced (but still measurable) levels of sterol esters in their tissues, had no detectable PSAT activity in the microsomal fractions, suggesting that Arabidopsis possess other enzyme(s) capable of acylating sterols. The AtPSAT is the only intracellular enzyme found so far that catalyzes an acyl-CoA-independent sterol ester formation. Thus, PSAT has a similar physiological function in plant cells as the unrelated acyl-CoA:sterol acyltransferase has in animal cells. PMID:16020547
Banas, Antoni; Carlsson, Anders S; Huang, Bangquan; Lenman, Marit; Banas, Walentyna; Lee, Michael; Noiriel, Alexandre; Benveniste, Pierre; Schaller, Hubert; Bouvier-Navé, Pierrette; Stymne, Sten
Plant sterol metabolism. ?(7)-Sterol-C5-desaturase (STE1/DWARF7), ?(5,7)-sterol-?(7)-reductase (DWARF5) and ?(24)-sterol-?(24)-reductase (DIMINUTO/DWARF1) show multiple subcellular localizations in Arabidopsis thaliana (Heynh) L.
Sterols are crucial lipid components that regulate membrane permeability and fluidity and are the precursors of bioactive steroids. The plant sterols exist as three major forms, free sterols, steryl glycosides and steryl esters. The storage of steryl esters in lipid droplets has been shown to contribute to cellular sterol homeostasis. To further document cellular aspects of sterol biosynthesis in plants, we addressed the question of the subcellular localization of the enzymes implicated in the final steps of the post-squalene biosynthetic pathway. In order to create a clear localization map of steroidogenic enzymes in cells, the coding regions of ?(7)-sterol-C(5)-desaturase (STE1/DWARF7), ?(24)-sterol-?(24)-reductase (DIMINUTO/DWARF1) and ?(5,7)-sterol-?(7)-reductase (DWARF5) were fused to the yellow fluorescent protein (YFP) and transformed into Arabidopsis thaliana mutant lines deficient in the corresponding enzymes. All fusion proteins were found to localize in the endoplasmic reticulum in functionally complemented plants. The results show that both ?(5,7)-sterol-?(7)-reductase and ?(24)-sterol-?(24)-reductase are in addition localized to the plasma membrane, whereas ?(7)-sterol-C(5)-desaturase was clearly detected in lipid particles. These findings raise new challenging questions about the spatial and dynamic cellular organization of sterol biosynthesis in plants. PMID:23409184
Silvestro, Daniele; Andersen, Tonni Grube; Schaller, Hubert; Jensen, Poul Erik
Plant Sterol Metabolism. ?7-Sterol-C5-Desaturase (STE1/DWARF7), ?5,7-Sterol-?7-Reductase (DWARF5) and ?24-Sterol-?24-Reductase (DIMINUTO/DWARF1) Show Multiple Subcellular Localizations in Arabidopsis thaliana (Heynh) L
Sterols are crucial lipid components that regulate membrane permeability and fluidity and are the precursors of bioactive steroids. The plant sterols exist as three major forms, free sterols, steryl glycosides and steryl esters. The storage of steryl esters in lipid droplets has been shown to contribute to cellular sterol homeostasis. To further document cellular aspects of sterol biosynthesis in plants, we addressed the question of the subcellular localization of the enzymes implicated in the final steps of the post-squalene biosynthetic pathway. In order to create a clear localization map of steroidogenic enzymes in cells, the coding regions of ?7-sterol-C5-desaturase (STE1/DWARF7), ?24-sterol-?24-reductase (DIMINUTO/DWARF1) and ?5,7-sterol-?7-reductase (DWARF5) were fused to the yellow fluorescent protein (YFP) and transformed into Arabidopsis thaliana mutant lines deficient in the corresponding enzymes. All fusion proteins were found to localize in the endoplasmic reticulum in functionally complemented plants. The results show that both ?5,7-sterol-?7-reductase and ?24-sterol-?24-reductase are in addition localized to the plasma membrane, whereas ?7-sterol-C5-desaturase was clearly detected in lipid particles. These findings raise new challenging questions about the spatial and dynamic cellular organization of sterol biosynthesis in plants.
Silvestro, Daniele; Andersen, Tonni Grube; Schaller, Hubert; Jensen, Poul Erik
Plant sterols and cardiovascular disease: a systematic review and meta-analysis†
The impact of increased serum concentrations of plant sterols on cardiovascular risk is unclear. We conducted a systematic review and meta-analysis aimed to investigate whether there is an association between serum concentrations of two common plant sterols (sitosterol, campesterol) and cardiovascular disease (CVD). We systematically searched the databases MEDLINE, EMBASE, and COCHRANE for studies published between January 1950 and April 2010 that reported either risk ratios (RR) of CVD in relation to serum sterol concentrations (either absolute or expressed as ratios relative to total cholesterol) or serum sterol concentrations in CVD cases and controls separately. We conducted two meta-analyses, one based on RR of CVD contrasting the upper vs. the lower third of the sterol distribution, and another based on standardized mean differences between CVD cases and controls. Summary estimates were derived by fixed and random effects meta-analysis techniques. We identified 17 studies using different designs (four case–control, five nested case–control, three cohort, five cross-sectional) involving 11 182 participants. Eight studies reported RR of CVD and 15 studies reported serum concentrations in CVD cases and controls. Funnel plots showed evidence for publication bias indicating small unpublished studies with non-significant findings. Neither of our meta-analyses suggested any relationship between serum concentrations of sitosterol and campesterol (both absolute concentrations and ratios to cholesterol) and risk of CVD. Our systematic review and meta-analysis did not reveal any evidence of an association between serum concentrations of plant sterols and risk of CVD.
Genser, Bernd; Silbernagel, Gunther; De Backer, Guy; Bruckert, Eric; Carmena, Rafael; Chapman, M. John; Deanfield, John; Descamps, Olivier S.; Rietzschel, Ernst R.; Dias, Karen C.; Marz, Winfried
Progress and prospective of plant sterol and plant stanol research: report of the Maastricht meeting.
Abundant evidence over past decades shows that foods with added plant sterols and plant stanols lower serum LDL cholesterol concentrations. However, despite the overwhelming data, numerous scientific questions still remain. The objective of this paper is to summarize the considerations of 60 academic and industrial experts who participated in the scientific meeting in Maastricht, the Netherlands, on issues related to the health effects of plant sterols and plant stanols. The meeting participants discussed issues including efficacy profiling, heterogeneity in responsiveness, effects beyond LDL-C lowering, and food formulation aspects of plant sterol and stanol consumption. Furthermore, aspects related to the potential atherogenicity of elevated circulatory plant sterol concentrations were discussed. Until the potential atherogenicity of plant sterols is resolved, based on the results >200 clinical trials, the risk to benefit of plant sterol use is favorable. Evidence on these topics in plant sterol and plant stanol research was presented and used to reach consensus where possible. It was concluded that endpoint studies looking at plant sterol and plant stanol efficacy are needed, however, there was no clear opinion on the best marker and best design for such a study. Based on the current scientific evidence, plant sterols and plant stanols are recommended for use as dietary options to lower serum cholesterol. PMID:23083678
Plat, J; Mackay, D; Baumgartner, S; Clifton, P M; Gylling, H; Jones, P J H
Although most of us are more or less familiar with the term "cholesterol", the world of sterols is far more complicated and interesting. Apart from cholesterol, many non-cholesterol sterols can be found in human plasma and these sterols serve many important functions in human organism. They are either derived from endogenous biosynthesis of cholesterol or they come from dietary sources (phytosterols). The sole cholesterol molecule is used for keeping our cell membranes fit, for signalization purposes as well as a precursor for bile acids and steroid hormones. The compounds prior to cholesterol in its biosynthetic pathway were identified as vitamin D3 precursor, meiosis activating sterols and nowadays it seems that they could play a role in cholesterol homeostasis. The sterols from ingested vegetable sources, the phytosterols, are expelled from enterocytes and thus indirectly help our gut in coping with abundant cholesterol in the lumen. Higher plants synthesize many phytosterols, but in marine organisms, we can find other innumerous sterol molecules. The diversity of sterol molecules produced and resistance of their tetracyclic core to enzymatic activities implies crucial importance of sterols during the ontogenesis of multicellular organisms. First oxygen appeared on the Earth app. 2.7 billion years ago and since that time, every new life form took the advantage of oxygen needed also for build-up of sterol molecules. The last decades changed our view to the sterol molecules on almost at all levels of their appearance in human body. In the gut, the absorption of sterols was proven to be protein dependent and the quest for the transporter was successful. The general concepts of intracellular homeostasis of cholesterol have been described including the covalent interaction unbelievable so far - cholesterol and a protein. The clinical importance of non-cholesterol sterols rises with the effort to discover underlying facts about the causes of atherosclerosis. The compound in question, cholesterol, seems to be involved, but it sounds not to be crucial per se. The fact that the accumulation of phytosterols in sitosterolemia enhances the probability of early atherosclerosis onset further supports the hypothesis about some sterol (or steroid) compound being responsible on the molecular level for triggering the pathobiochemical cascade of events leading to atherosclerosis. Understanding the processes taking place in the enterocyte during the absorption of sterols resulted in synthesis of selective inhibitors at the level of sterol translocation into the enterocyte, sterol esterification and chylomicron packing, which are in different phases of clinical testing. The studies in the last part of the monograph represent the clinical potential of the analyses of non-cholesterol sterols. In well-defined groups, these analytes enables us to assess the changes in the homeostasis of cholesterol, which can be reflected in the concentration of total cholesterol. Furthermore, the high concentrations of some plasma sterols could point to the inborn errors of cholesterol biosynthesis (Smith-Laemli-Opitz syndrome), transport (sitosterolemia) or metabolization (cerebrotendinous xanthomatosis). Some issues concerning the research on the non-cholesterol sterols still remain unanswered - it is not known why some of the enzymes of the cholesterol biosynthesis (seladin-1, sterol D14 reductase) have other functions, qualitative aspects of sterol absorption are not satisfactorily explained and exact reason for expulsion of phytosterols from human body is not clear. Nevertheless, the authors hope that the presented facts can broaden the reader's perspective about the area, which is usually hidden beneath the cholesterol molecule. PMID:19283968
Vecka, Marek; Zak, Ales; Tvrzická, Eva
Hypocholesterolaemic effects of plant sterol analogues are independent of ABCG5 and ABCG8 transporter expressions in hamsters.
The hypolipidaemic effects of plant sterols are well established. However, mechanisms by which plant sterols lower plasma cholesterol levels, particularly at the molecular level, have not been clearly elucidated. The objective of the present study was to determine whether different plant sterol analogues reduce plasma cholesterol levels by up regulating the sterol transporters ABCG5 and ABCG8 in the liver and/or small intestine. Male Golden Syrian hamsters were divided into eight groups. Groups 1 and 2 were fed a maize starch-casein-sucrose-based diet that did not contain cholesterol (control; Con) or the Con diet with the addition of 0.25 % cholesterol (Ch-Con). Groups 3-8 were fed the Ch-Con diet supplemented with 1 % plant sterols, 1 % plant stanols, 1 % of a plant sterol and stanol mixture (50:50), 1.76 % plant sterol-fish oil esters, or 0.71 or 1.43 % stanol-ascorbic acid esters, respectively. After 5 weeks, the Ch-Con diet up regulated the ABCG5 mRNA expression and tended (P = 0.083) to increase ABCG8 mRNA expression in the liver, but did not affect both genes' expression in the small intestine compared with the Con diet. Hamsters fed 0.7 % stanol esters showed lower plasma cholesterol levels (P < 0.001) and also lower liver ABCG5 mRNA expression (P < 0.05) compared with the Ch-Con diet. Plant stanols, stanol esters, and sterol esters did not affect the ABCG5 or ABCG8 mRNA expressions in the liver and intestine although they reduced plasma cholesterol levels. These results suggest that plant sterols and their derivatives reduce plasma cholesterol levels independently from the mRNA expression of ABCG5 and ABCG8 transporters. PMID:17459188
Jia, Xiaoming; Ebine, Naoyuki; Demonty, Isabelle; Wang, Yanwen; Beech, Robin; Muise, Victoria; Fortin, Marc G; Jones, Peter J H
Plant Sterol Levels Are Not Associated With Atherosclerosis in Mice and Men
Objective—Sitosterolemia is characterized by elevated plasma levels of plant sterols, hypercholesterolemia and premature coronary heart disease (CHD). CHD develops in some subjects with sitosterolemia, despite having normal plasma cholesterol levels, suggesting that high circulating levels of plant sterols may be atherogenic. We tested whether elevated plasma levels of plant sterols (sitosterol and campesterol) were associated with atherosclerosis in genetically modified
Kenneth R. Wilund; Liqing Yu; Fang Xu; Gloria Vega; Scott Grundy; Jonathan C. Cohen; Helen H. Hobbs
No Association Between Plasma Levels of Plant Sterols and Atherosclerosis in Mice and Men
Objective—Sitosterolemia is characterized by elevated plasma levels of plant sterols, hypercholesterolemia and premature coronary heart disease (CHD). CHD develops in some subjects with sitosterolemia, despite having normal plasma cholesterol levels, suggesting that high circulating levels of plant sterols may be atherogenic. We tested whether elevated plasma levels of plant sterols (sitosterol and campesterol) were associated with atherosclerosis in genetically modified
Kenneth R. Wilund; Liqing Yu; Fang Xu; Gloria L. Vega; Scott M. Grundy; Jonathan C. Cohen; Helen H. Hobbs
Comparison of the intestinal uptake of cholesterol, plant sterols, and stanols in mice
The recent identification of the aberrant transport proteins ABCG5 and ABCG8 resulting in sitosterolemia sug- gests that intestinal uptake of cholesterol is an unselective process, and that discrimination between cholesterol and plant sterols takes place at the level of sterol efflux from the enterocyte. Although plant sterols are structurally very simi- lar to cholesterol, differing only in their side chain
Michael Igel; Uwe Giesa; Dieter Lütjohann; Klaus von Bergmann
Bile acids and sterols in urban sewage treatment plants.
The composition of bile acids, sterols and sterones in water and sludge from an urban sewage treatment plant has been examined for assessment of the possible use of these compounds as pollution biomarkers. Samples were solvent-extracted, hydrolysed, and fractionated by column chromatography to separate acids, hydrocarbons, sterones and sterols. These fractions, except hydrocarbons, were methylated (acids only) and silylated for instrumental analysis. Gas chromatographic-mass spectrometric analysis was performed in the electron-impact mode, using a non-polar capillary column. Lithocholic acids (3alpha- and 3beta-epimers), coprostanone, coprostanol, cholesterol, cholestenone, and cholestanone were found in sludge and all waters. However, the waters after secondary plant treatment contained mainly lithocholic acids epimers and coprostanone, pointing to these compounds as potential markers for urban treatment plant effluents in natural waters courses. PMID:11572384
Chaler, R; Simoneit, B R; Grimalt, J O
Efficacy and Safety of Plant Stanols and Sterols in the Management of Blood Cholesterol Levels
Foods with plant stanol or sterol esters lower serum cho- lesterol levels. We summarize the deliberations of 32 ex- perts on the efficacy and safety of sterols and stanols. A meta-analysis of 41 trials showed that intake of 2 g\\/d of stanols or sterols reduced low-density lipoprotein (LDL) by 10%; higher intakes added little. Efficacy is similar for sterols and
[Plant sterols as dietary supplements for the prevention of cardiovascular diseases].
"Functional foods" supplemented with plant sterols are advertised and added to regular meals to reduce serum cholesterol concentrations. The effects of increased phytosterol levels on cardiovascular diseases, however, are not known. Findings in patients with sitosterolemia, data from epidemiological studies, and experimental data from animal studies suggest that plant sterols may potentially exert negative cardiovascular effects. Additional studies investigating relevant clinical endpoints are needed before a diet supplemented with plant sterols can be recommended in the prevention of cardiovascular diseases. PMID:18491276
Weingärtner, O; Böhm, M; Laufs, U
Absorption, excretion, and distribution of plant sterols after proximal gut resection and autotransplantation of porcine ileum
Contribution of different gut segments to plant sterol absorption, adaptation of plant sterol absorption after partial small\\u000a bowel resection, and effects of gut transplantation (necessitates extrinsic autonomic denervation and lymphatic disruption)\\u000a on plant sterol biodynamics are unclear. We studied the consequences of massive proximal small bowel resection and autotransplantation\\u000a of the remaining ileum on the adaptive absorption and biodynamics of
M. P. Pakarinen; J. Halttunen; P. Kuusanmäki; J. Lauronen; T. A. Miettinen
Plant sterol biosynthesis: identification of two distinct families of sterol 4alpha-methyl oxidases.
In plants, the conversion of cycloartenol into functional phytosterols requires the removal of the two methyl groups at C-4 by an enzymic complex including a sterol 4alpha-methyl oxidase (SMO). We report the cloning of candidate genes for SMOs in Arabidopsis thaliana, belonging to two distinct families termed SMO1 and SMO2 and containing three and two isoforms respectively. SMO1 and SMO2 shared low sequence identity with each other and were orthologous to the ERG25 gene from Saccharomyces cerevisiae which encodes the SMO. The plant SMO amino acid sequences possess all the three histidine-rich motifs (HX3H, HX2HH and HX2HH), characteristic of the small family of membrane-bound non-haem iron oxygenases that are involved in lipid oxidation. To elucidate the precise functions of SMO1 and SMO2 gene families, we have reduced their expression by using a VIGS (virus-induced gene silencing) approach in Nicotiana benthamiana. SMO1 and SMO2 cDNA fragments were inserted into a viral vector and N. benthamiana inoculated with the viral transcripts. After silencing with SMO1, a substantial accumulation of 4,4-dimethyl-9beta,19-cyclopropylsterols (i.e. 24-methylenecycloartanol) was obtained, whereas qualitative and quantitative levels of 4alpha-methylsterols were not affected. In the case of silencing with SMO2, a large accumulation of 4alpha-methyl-Delta7-sterols (i.e. 24-ethylidenelophenol and 24-ethyllophenol) was found, with no change in the levels of 4,4-dimethylsterols. These clear and distinct biochemical phenotypes demonstrate that, in contrast with animals and fungi, in photosynthetic eukaryotes, these two novel families of cDNAs are coding two distinct types of C-4-methylsterol oxidases controlling the level of 4,4-dimethylsterol and 4alpha-methylsterol precursors respectively.
Darnet, Sylvain; Rahier, Alain
Plant sterol and stanol substrate specificity of pancreatic cholesterol esterase.
Consumption of plant sterols or stanols (collectively referred to as phytosterols) and their esters results in decreased low-density lipoprotein cholesterol, which is associated with decreased atherosclerotic risk. The mechanisms by which phytosterols impart their effects, however, are incompletely characterized. The objective of the present study is to determine if pancreatic cholesterol esterase (PCE; EC 126.96.36.199), the enzyme primarily responsible for cholesterol ester hydrolysis in the digestive tract, is capable of hydrolyzing various phytosterol esters and to compare the rates of sterol ester hydrolysis in vitro. We found that PCE hydrolyzes palmitate, oleate and stearate esters of cholesterol, stigmasterol, stigmastanol and sitosterol. Furthermore, we found that the rate of hydrolysis was dependent on both the sterol and the fatty acid moieties in the following order of rates of hydrolysis: cholesterol>(sitosterol=stigmastanol)>stigmasterol; oleate>(palmitate=stearate). The addition of free phytosterols to the system did not change hydrolytic activity of PCE, while addition of palmitate, oleate or stearate increased activity. Thus, PCE may play an important but discriminatory role in vivo in the liberation of free phytosterols to compete with cholesterol for micellar solubilization and absorption. PMID:19615880
Brown, Andrew W; Hang, Jiliang; Dussault, Patrick H; Carr, Timothy P
Effects of various amounts of dietary plant sterol esters on plasma and hepatic sterol concentration and aortic foam cell formation of cholesterol-fed hamsters
Dietary intake of plant sterol esters (PSE) lowers plasma LDL-cholesterol (LDL-C), but can modestly increase plasma plant sterol concentrations. The objective of the present study was to investigate the impact of increasing doses of dietary PSE on plasma and liver sterol concentrations as well as on aortic foam cell development as a marker of atherogenesis. One-hundred and twenty F1B hybrid
Fady Y. Ntanios; Aart J. van de Kooij; Emile A. M. de Deckere; Elke A. Trautwein
Molecular characterization and functional analysis of Glycine max sterol methyl transferase 2 genes involved in plant membrane sterol biosynthesis
Sterol C24 methyltransferase (SMT2) genes governing the pattern of phytosterols synthesized in higher plants have been studied in Glycine seedlings and wild-type and engineered Arabidopsis thaliana plants. The SMT2 genes of soybean (SMT2-1 and SMT2-2) previously cloned and characterized (Neelakandan et al. 2009) were shown to complement the SMT deficient cvp1 mutant Arabidopsis plants, consistent with their role in regulation
Anjanasree K. Neelakandan; Hanh T. M. Nguyen; Rajesh Kumar; Lam-Son Phan Tran; Satish K. Guttikonda; Truyen Ngoc Quach; Donovan L. Aldrich; W. David Nes; Henry T. Nguyen
Plant sterols and stanols: effects on mixed micellar composition and LXR (target gene) activation
Plant stanols and sterols of the 4-desmethyl fam- ily (e.g., sitostanol and sitosterol) effectively decrease LDL cholesterol concentrations, whereas 4,4-dimethylsterols ( ? -amyrin and lupeol) do not. Serum carotenoid concentra- tions, however, are decreased by both plant sterol families. The exact mechanisms underlying these effects are not known, although effects on micellar composition have been suggested. With a liver X
Jogchum Plat; Jason A. Nichols; Ronald P. Mensink
Plant sterols and stanols as cholesterol-lowering ingredients in functional foods.
This article reviews developments related to the use of plant sterols and stanols as cholesterol-lowering ingredients in foods and nutraceuticals preparations. Plant sterols and stanols are extracted from the deodorizer distillates of vegetable oil refining and from tall oil, a by-product of paper pulping industry. Plant sterols/stanols inhibit cholesterol absorption possibly by competitively inhibiting its incorporation into the mixed micelles in the small intestine although other mechanisms can not be excluded. Daily consumption of 1-2 grams of plant sterols or stanols was shown to cause 10-20% reduction in low-density lipoprotein cholesterol (LDL cholesterol). Combinations of plant sterols/stanols with certain lipid-lowering ingredients were shown to potentate their cholesterol-lowering effects and, in some cases, add triacylglycerol-lowering effects. In this article, patents based information is also discussed. PMID:20653521
Kamal-Eldin, Afaf; Moazzami, Ali
Sitosterolemia--a rare disease. Are elevated plant sterols an additional risk factor?
Elevated plasma plant sterol concentrations, xanthomatosis, and accelerated-often fatal-atherosclerosis at young age are the major findings in patients with homozygous sitosterolemia. A defect in the ABCG5 or ABCG8 co-transporter gene locus (STSL) causes an increased intestinal absorption and a decreased biliary elimination of all sterols, plant sterols as well as cholesterol, leading to a 50 to 200-fold increase in plasma plant sterol concentrations. A few recent publications indicate that even moderately elevated plasma plant sterol levels might be associated with an increased risk of atherosclerosis. This raises the question whether plant sterols themselves might be atherogenic or whether elevated plasma levels are a marker for a decreased ABCG5/G8 transporter activity which itself causes an increased risk for atherosclerosis. However, current data are too few to conclude that elevated plant sterol concentrations in plasma are an additional risk factor for coronary heart disease. But especially young patients suffering from xanthomatosis and/or atherosclerotic diseases with only mildly or moderately elevated plasma cholesterol should be screened for sitosterolemia by measurement of plasma plant sterol levels. PMID:15599566
Sudhop, T; von Bergmann, K
Efficacy and safety of plant stanols and sterols in the control of blood cholesterol levels
Foods with plant stanol or sterol esters lower serum cholesterol levels. We summarize the deliberations of 32 experts on the efficacy and safety of sterols and stanols. A meta-analysis of 41 trials showed that intake of 2 g\\/d ofstanols or sterols reduced low-density lipoprotein (LDL)by 10%; higher intakes added little. Efficacy is similar forsterols and stanols, but the food form
M. B. Katan; S. M. Grundy; P. J. H. Jones; M. R. Law; T. Miettinen; R. Paoletti
Cholesterol metabolism and serum non-cholesterol sterols: summary of 13 plant stanol ester interventions
Background The efficacy and safety of plant stanols added to food products as serum cholesterol lowering agents have been demonstrated convincingly, but their effects on cholesterol metabolism and on serum non-cholesterol sterols is less evaluated. The aim of this study was to assess the validity of serum non-cholesterol sterols and squalene as bioindices of cholesterol synthesis and absorption, and to examine how the individual serum non-cholesterol sterols respond to consumption of plant stanols. Methods We collected all randomized, controlled plant stanol ester (STAEST) interventions in which serum cholestanol, plant sterols campesterol and sitosterol, and at least two serum cholesterol precursors had been analysed. According to these criteria, there was a total of 13 studies (total 868 subjects without lipid-lowering medication; plant stanol doses varied from 0.8 to 8.8 g/d added in esterified form; the duration of the studies varied from 4 to 52 weeks). Serum non-cholesterol sterols were assayed with gas–liquid chromatography, cholesterol synthesis with the sterol balance technique, and fractional cholesterol absorption with the dual continuous isotope feeding method. Results The results demonstrated that during the control and the STAEST periods, the serum plant sterol/cholesterol- and the cholestanol/cholesterol-ratios reflected fractional cholesterol absorption, and the precursor sterol/cholesterol-ratios reflected cholesterol synthesis. Plant sterol levels were dose-dependently reduced by STAEST so that 2 g of plant stanols reduced serum campesterol/cholesterol-ratio on average by 32%. Serum cholestanol/cholesterol-ratio was reduced less frequently than those of the plant sterols by STAEST, and the cholesterol precursor sterol ratios did not change consistently in the individual studies emphasizing the importance of monitoring more than one surrogate serum marker. Conclusions Serum non-cholesterol sterols are valid markers of cholesterol absorption and synthesis even during cholesterol absorption inhibition with STAEST. Serum plant sterol concentrations decrease dose-dependently in response to plant stanols suggesting that the higher the plant stanol dose, the more cholesterol absorption is inhibited and the greater the reduction in LDL cholesterol level is that can be achieved. Trial registration Clinical Trials Register # NCT00698256 [Eur J Nutr 2010, 49:111-117
Optimisation of plant sterols incorporation in human keratinocyte plasma membrane and modulation of membrane fluidity
The in vitro effects of plant sterols were investigated with regard to their uptake and membrane lipid fluidity in human keratinocytes. Among the different media tested to transport sterols (liposomes, micelles and organic solvents), the best results in terms of incorporation and viability were obtained by the use of the organic solvents dimethylsulfoxide and ethanol. After 48 h incubation exogenous
M. P Mora; C Tourne-Peteilh; M Charveron; B Fabre; A Milon; I Muller
Differential Effects of Plant Sterols on Water Permeability and on Acyl Chain Ordering of Soybean Phosphatidylcholine Bilayers
To gain some insight into the structural and functional roles of sterols in higher plant cells, various plant sterols have been incorporated into soybean phosphatidylcholine (PtdCho) bilayers and tested for their ability to regulate water permeability and acyl chain ordering. Sitosterol was the most efficient sterol in reducing the water permeability of these vesicles and stigmasterol appeared to have no
Isabelle Schuler; Alain Milon; Yoichi Nakatani; Guy Ourisson; Anne-Marie Albrecht; Pierre Benveniste; Marie-Andree Hartman
Consumption of a plant sterol-based spread derived from rice bran oil is effective at reducing plasma lipid levels in mildly hypercholesterolaemic individuals.
To establish the effectiveness of a new phytosterol-containing spread derived from rice bran oil (RBO), a randomised, double-blind, cross-over human clinical trial was conducted over 12 weeks. A total of eighty mildly hypercholesterolaemic (total blood cholesterol level ? 5 and ? 7·5 mmol/l with a serum TAG level of ? 4·5 mmol/l) individuals were randomised into two groups (n 40). Group 1 consumed spread only daily for 4 weeks. They were randomised to consume 20 g RBO spread (RBOS), 20 g standard spread (SS) or 20 g phytosterol-enriched spread (PS). After a 4-week period, individuals changed to the next randomised treatment until all three treatments had been consumed. Group 2 consumed spread plus oil daily for 4 weeks. They consumed 20 g RBOS plus 30 ml RBO, 20 g SS plus 30 ml sunflower oil or 20 g RBOS. Blood samples were collected for the analysis of lipid parameters, and 3 d diet records were collected. Compared with SS, RBOS significantly reduced total cholesterol by 2·2 % (P = 0·045), total cholesterol:HDL by 4·1 % (P = 0·005) and LDL-cholesterol by 3·5 % (P = 0·016), but was not as effective overall as PS, which reduced total cholesterol by 4·4 % (P = 0·001), total cholesterol:HDL by 3·4 % (P = 0·014) and LDL-cholesterol by 5·6 % (P = 0·001). In group 2, the addition of RBO to the RBOS produced no differences in cholesterol levels. These results confirm that RBOS is effective in lowering serum cholesterol when consumed as part of a normal diet. PMID:21320365
Eady, Sarah; Wallace, Alison; Willis, Jinny; Scott, Russell; Frampton, Chris
Effects of plant sterols and stanols on intestinal cholesterol metabolism: suggested mechanisms from past to present.
Plant sterols and stanols are natural food ingredients found in plants. It was already shown in 1950 that they lower serum low-density lipoprotein cholesterol (LDL-C) concentrations. Meta-analysis has reported that a daily intake of 2.5 g plant sterols/stanols reduced serum LDL-C concentrations up to 10%. Despite many studies, the underlying mechanism remains to be elucidated. Therefore, the proposed mechanisms that have been presented over the past decades will be described and discussed in the context of the current knowledge. In the early days, it was suggested that plant sterols/stanols compete with intestinal cholesterol for incorporation into mixed micelles as well as into chylomicrons. Next, the focus shifted toward cellular processes. In particular, a role for sterol transporters localized in the membranes of enterocytes was suggested. All these processes ultimately lowered intestinal cholesterol absorption. More recently, the existence of a direct secretion of cholesterol from the circulation into the intestinal lumen was described. First results in animal studies suggested that plant sterols/stanols activate this pathway, which also explains the increased fecal neutral sterol content and as such could explain the cholesterol-lowering activity of plant sterols/stanols. PMID:22623436
De Smet, Els; Mensink, Ronald P; Plat, Jogchum
Plant sterols and host plant suitability for generalist and specialist caterpillars.
Insects, unlike plants and vertebrates, lack the ability to biosynthesize sterols. Cholesterol is typically the most common sterol found in plant-feeding insects, but it is rarely found in plants above trace levels, so plant-feeding insects must produce the cholesterol they need by metabolizing the sterols found in the plants they eat. Plant-feeding insects are, however, often limited in terms of which sterols can be converted to cholesterol. In the current study we used a transgenic tobacco plant line that displays high levels of atypical plant steroids, specifically stanols and ketone-steroids, to explore how novel steroid structural features affect performance in three economically important caterpillars (Heliothis virescens, Spodoptera exigua, and Manduca sexta). For each species we measured pupation success, larval development, pupal mass, pupal development, and eclosion success. For the two generalists species (H. virescens and S. exigua) we also measured egg production and egg viability. We then used these eggs to replicate the experiment, so that we could examine the effect of parental steroid dietary history on survival, growth and reproduction of 2nd-generation individuals. Significant negative effects of novel steroids on larval and pupal performance were observed for each caterpillar in the first generation, although these were often subtle, and were not consistent between the three species. In the second generation, larval survival estimated by 'pupation number/plant' on the tobacco plants with novel steroids was significantly reduced, while eclosion success was significantly lower for H. virescens. With respect to adult reproduction (i.e. egg production and egg viability) there were no observed differences in the first generation, but novel steroids significantly negatively impacted reproduction in the second generation. The findings from this study, when integrated into a simple population growth model, demonstrate the potential in using plants with modified steroids as a novel approach to manage populations of economically important caterpillar species. PMID:22154836
Jing, Xiangfeng; Grebenok, Robert J; Behmer, Spencer T
Tocopherol, tocotrienol and plant sterol contents of vegetable oils and industrial fats
The tocopherol and tocotrienol (i.e. tocol) and plant sterol contents of 14 vegetable and 9 industrial fats and oils available on the Finnish market in 2005 were determined using NP-HPLC with fluorescence detection (tocols) and GC-FID (plant sterols). Best sources of ?-tocopherol were wheat germ (192mg\\/100g) and sunflower oil (59mg\\/100g). Oils richest in ?-tocopherol were camelina (72mg\\/100g), linseed (52mg\\/100g) and
Heidi Schwartz; Velimatti Ollilainen; Vieno Piironen; Anna-Maija Lampi
Transcription of sterol Delta(5,6)-desaturase and sterol 14alpha-demethylase is induced in the plant pathogenic ascomycete, Leptosphaeria maculans, during treatment with a triazole fungicide.
Two genes whose derived amino acid sequences closely resemble the ergosterol biosynthetic enzymes, sterol Delta(5,6)-desaturase (erg3) and sterol 14alpha-demethylase (erg11), were cloned from the plant pathogenic fungus Leptosphaeria maculans. Transcript levels of both these genes increased following exposure of L. maculans to the triazole fungicide, flutriafol, which specifically inhibits the ergosterol biosynthetic pathway. This induction may be due to a decrease in ergosterol content or to abnormal levels of the ergosterol precursor, 24-methylene dihydrolanosterol. PMID:12445649
Griffiths, Katherine M; Howlett, Barbara J
Current therapy for patients with sitosterolemia--effect of ezetimibe on plant sterol metabolism.
Sitosterolemia is a rare, autosomal recessive inherited sterol storage disease associated with high tissue and serum plant sterol concentrations, caused by mutations in the adenosine triphosphate-bind-ing cassette (ABC) transporter ABCG5 or ABCG8 genes. Markedly increased serum concentration of plant sterols. such as sitosterol and campesterol, cause premature atherosclerosis and massive xanthomas. Hitherto known treatments for sitosterolemia, including a low-sterol diet, bile-salt binding resins, ileal bypass surgery and low density lipoprotein (LDL) apheresis have not yielded sufficient reduction of serum plant sterol levels and many patients show a sustained elevation of plant sterol levels, subsequently developing premature atherosclerotic cardiovascular diseases. Ezetimibe, an inhibitor of intestinal cholesterol absorption through its binding to Niemann-Pick C1-like 1 (NPC1L1), has been widely used for decreasing serum LDL-cholesterol levels in patients with hypercholesterolemia. Ezetimibe also reduces the gastrointestinal absorption of plant sterols, thereby also lowering the serum concentrations of plant sterols. This pharmacological property of ezetimibe shows its potential as a novel effective therapy for sitosterolemia. In the current review, we discuss the current therapy for patients with sitosterolemia and present two Japanese adolescent patients with this disease, one of whom underwent percutaneous coronary intervention for accelerated coronary atherosclerosis. Ezetimibe administration in addition to conventional drug therapy successfully reduced serum sitosterol levels by 51.3% and 48.9%, respectively, in the two patients, demonstrating ezetimibe as a novel and potent treatment agent for sitosterolemia that could work additively with conventional drug therapy. PMID:20543520
Tsubakio-Yamamoto, Kazumi; Nishida, Makoto; Nakagawa-Toyama, Yumiko; Masuda, Daisaku; Ohama, Tohru; Yamashita, Shizuya
Serum lipids, plant sterols, and cholesterol kinetic responses to plant sterol supplementation in phytosterolemia heterozygotes and control individuals123
Background: Plant sterol (PS) supplementation is increasingly accepted as a dietary strategy to lower plasma cholesterol concentrations. However, information is scarce about the effect of increased PS intake in potentially vulnerable groups, such as phytosterolemia heterozygotes (HET). Objective: This study assessed the responsiveness of circulating PS and lipid concentrations and cholesterol kinetics (absorption and synthesis) to daily PS supplementation in HET (ABCG8 S107X mutation) compared with a healthy control cohort. Design: A double-blind, randomized, crossover, placebo-controlled study was conducted in 10 HET and 15 control subjects. The participants had a mean (±SEM) age of 34 ± 2 y and a BMI (in kg/m2) of 29.9 ± 1.1 and consumed ?1.6 g PS or placebo capsules daily with supper for 4 wk. Cholesterol absorption and synthesis were assessed by using [13C]cholesterol and deuterium oxide, respectively. Results: Plasma LDL-cholesterol concentrations decreased (P = 0.006) in both groups after PS supplementation (HET: 2.73 ± 0.19 mmol/L; control: 3.11± 0.19 mmol/L) compared with placebo (HET: 3.12 ± 0.20 mmol/L; control: 3.50 ± 0.21 mmol/L), whereas PS concentrations (campesterol+?-sitosterol) increased (P = 0.03) in both groups after PS supplementation (HET: 39.72 ± 6.05 ?mol/L; control: 24.03 ± 1.65 ?mol/L) compared with placebo (HET: 27.32 ± 3.80 ?mol/L; control: 21.12 ± 2.05 ?mol/L). Cholesterol absorption efficiency decreased (P = 0.010) by ?22% and ?17% and synthesis rates increased (P = 0.040) by ?20% and ?24% in the HET and control groups, respectively, in response to PS consumption compared with placebo. Conclusion: These data suggest that heterozygosity for the ABCG8 S107X mutation does not influence the action of dietary PS on circulating cholesterol concentrations but may affect sterol absorption. This trial was registered at clinicaltrials.gov as NCT01102647.
Myrie, Semone B; Mymin, David; Triggs-Raine, Barbara; Jones, Peter JH
Plant sterols: factors affecting their efficacy and safety as functional food ingredients
Plant sterols are naturally occurring molecules that humanity has evolved with. Herein, we have critically evaluated recent literature pertaining to the myriad of factors affecting efficacy and safety of plant sterols in free and esterified forms. We conclude that properly solubilized 4-desmetyl plant sterols, in ester or free form, in reasonable doses (0.8–1.0 g of equivalents per day) and in various vehicles including natural sources, and as part of a healthy diet and lifestyle, are important dietary components for lowering low density lipoprotein (LDL) cholesterol and maintaining good heart health. In addition to their cholesterol lowering properties, plant sterols possess anti-cancer, anti-inflammatory, anti-atherogenicity, and anti-oxidation activities, and should thus be of clinical importance, even for those individuals without elevated LDL cholesterol. The carotenoid lowering effect of plant sterols should be corrected by increasing intake of food that is rich in carotenoids. In pregnant and lactating women and children, further study is needed to verify the dose required to decrease blood cholesterol without affecting fat-soluble vitamins and carotenoid status.
Berger, Alvin; Jones, Peter JH; Abumweis, Suhad S
START lipid\\/sterol-binding domains are amplified in plants and are predominantly associated with homeodomain transcription factors
BACKGROUND: In animals, steroid hormones regulate gene expression by binding to nuclear receptors. Plants lack genes for nuclear receptors, yet genetic evidence from Arabidopsis suggests developmental roles for lipids\\/sterols analogous to those in animals. In contrast to nuclear receptors, the lipid\\/sterol-binding StAR-related lipid transfer (START) protein domains are conserved, making them candidates for involvement in both animal and plant lipid\\/sterol
Kathrin Schrick; Diana Nguyen; Wojciech M Karlowski; Klaus FX Mayer
Increased incorporation of dietary plant sterols and cholesterol correlates with decreased expression of hepatic and intestinal Abcg5 and Abcg8 in diabetic BB rats.
The aim of this study was to determine the impact of dietary plant sterols and stanols on sterol incorporation and sterol-regulatory gene expression in insulin-treated diabetic rats and nondiabetic control rats. Diabetic BioBreeding (BB) and control BB rats were fed a control diet or a diet supplemented with plant sterols or plant stanols (5 g/kg diet) for 4 weeks. Expression of sterol-regulatory genes in the liver and intestine was assessed by real-time quantitative polymerase chain reaction. Diabetic rats demonstrated increased tissue accumulation of cholesterol and plant sterols and stanols compared to control rats. This increase in cholesterol and plant sterols and stanols was associated with a marked decrease in hepatic and intestinal Abcg5 (ATP-binding cassette transporter G5) and Abcg8 (ATP-binding cassette transporter G8) expressions in diabetic rats, as well as decreased mRNA levels of several other genes involved in sterol regulation. Plant sterol or plant stanol supplementation induced the accumulation of plant sterols and stanols in tissues in both rat strains, but induced a greater accumulation of plant sterols and stanols in diabetic rats than in control rats. Surprisingly, only dietary plant sterols decreased cholesterol levels in diabetic rats, whereas dietary plant stanols caused an increase in cholesterol levels in both diabetic and control rats. Therefore, lower expression levels of Abcg5/Abcg8 in diabetic rats may account for the increased accumulation of plant sterols and cholesterol in these rats. PMID:18547796
Scoggan, Kylie A; Gruber, Heidi; Chen, Qixuan; Plouffe, Louise J; Lefebvre, Jaclyn M; Wang, Bingtuan; Bertinato, Jesse; L'Abbé, Mary R; Hayward, Stephen; Ratnayake, W M Nimal
Study of thermodynamic parameters for solubilization of plant sterol and stanol in bile salt micelles.
We investigated the difference between the molecular structures of plant sterols and stanols that affect the solubilization of cholesterol in bile salt micelles (in vitro study). First, the aqueous solubility of beta-sitosterol, beta-sitostanol, and campesterol was determined by considering the specific radioactivity by using a fairly small quantity of each radiolabeled compound. The order of their aqueous solubilities was as follows: cholesterol > campesterol > beta-sitostanol > beta-sitosterol. The maximum solubility of cholesterol and the above mentioned sterol/stanol in sodium taurodeoxycholate and sodium taurocholate solutions (single solubilizate system) was measured. Moreover, the preferential solubilization of cholesterol in bile salt solutions was systematically studied by using different types of plant sterols/stanols. The solubilization results showed that the cholesterol-lowering effect was similar for sterols and stanol. Thermodynamic analysis was applied to these experimental results. The Gibbs energy change (Delta G degrees ) for the solubilization of plant sterols/stanols showed a negative value larger than that for cholesterol. PMID:18544343
Matsuoka, Keisuke; Nakazawa, Tomomi; Nakamura, Ai; Honda, Chikako; Endo, Kazutoyo; Tsukada, Masamichi
Benefit-risk assessment of plant sterols in margarine: a QALIBRA case study.
This paper presents the benefit-risk assessment of adding plant sterols to margarine as an illustration of the QALIBRA method and software. With the QALIBRA tool health effects, risks as well as benefits are expressed in a common metric (DALY) which allows quantitative balancing of benefits and risks of food intake. The QALIBRA software can handle uncertainties in a probabilistic simulation. This simple case study illustrates the data need and assumptions that go into a quantitative benefit-risk assessment. The assessment shows that the benefits of plant sterols added to margarine outweigh the risks, if any. PMID:22981906
Hoekstra, Jeljer; Fransen, Heidi P; van Eijkeren, Jan C H; Verkaik-Kloosterman, Janneke; de Jong, Nynke; Owen, Helen; Kennedy, Marc; Verhagen, Hans; Hart, Andy
Plant sterols and stanols in the treatment of dyslipidemia: new insights into targets and mechanisms related to cardiovascular risk.
Plant sterols and stanols are naturally occurring constituents of plants and as such normal components of our daily diet. The consumption of foods enriched in plant sterols and stanols may help to reduce low-density lipoprotein cholesterol (LDL-C) concentrations. Meta-analyses have shown that consuming approximately 2.5 g plant sterols or stanols per day lowers serum LDL-C concentrations up to 10%, with little additional benefit achieved at higher intakes. However, recent studies evaluating plant stanol intakes up to 9 g/d have indicated that LDL-C concentrations can be reduced up to 17%, which suggests that more pronounced reductions can be achieved at higher intakes. Studies describing effects of high plant sterol intakes on serum LDL-C concentrations are not consistent. Besides the effects of higher than advocated intakes on serum LDL-C concentrations, several topics will be discussed in this review. First, besides the well-characterized effect of plant sterols and stanols on serum LDL-C concentrations, evidence is now emerging of their effects on triacylglycerol metabolism, which makes them highly attractive for interventions in metabolic syndrome-like populations. Secondly, there is an ongoing debate whether increased plant sterol concentrations are associated with an increased cardiovascular disease risk or not. For this there are at least two possible explanations. First, the potential atherogenicity of increased plant sterol concentrations might be ascribed to the formation of plant sterol oxidation products (so-called oxyphytosterols) or secondly, elevated serum plant sterol concentrations should only be seen as surrogate markers for characterizing subjects with high intestinal cholesterol absorption. Finally, we discuss recent studies, which suggest that plant sterols and stanols can improve endothelial dysfunction in subjects at risk, although evidence is limited and more research is needed. PMID:21418032
Baumgartner, Sabine; Mensink, Ronald P; Plat, Jogchum
Plasma plant sterols serve as poor markers of cholesterol absorption in man[S
The validation of the use of plasma plant sterols as a marker of cholesterol absorption is frail. Nevertheless, plant sterol concentrations are routinely used to describe treatment-induced changes in cholesterol absorption. Their use has also been advocated as a clinical tool to tailor cholesterol-lowering therapy. Prior to wider implementation, however, the validity of plant sterols as absorption markers needs solid evaluation. Therefore, we compared plasma plant sterol concentrations to gold-standard stable isotope-determined cholesterol absorption. Plasma campesterol/TC concentrations (camp/TC) were measured in a population of 175 mildly hypercholesterolemic individuals (age: 59.7 ± 5.6 years; BMI: 25.5 ± 2.9kg/m2; LDL-C: 4.01 ± 0.56 mmol/l). We compared cholesterol absorption according to the plasma dual-isotope method in subjects with the highest camp/TC concentrations (N = 41, camp/TC: 2.14 ± 0.68 ?g/mg) and the lowest camp/TC concentrations (N = 39, camp/TC: 0.97 ± 0.22 ?g/mg). Fractional cholesterol absorption did not differ between the groups (24 ± 12% versus 25 ± 16%, P = 0.60), nor was it associated with plasma camp/TC concentrations in the total population of 80 individuals (? = 0.13; P = 0.30, adjusted for BMI and plasma triglycerides). Our findings do not support a relation between plasma plant sterol concentrations and true cholesterol absorption and, therefore, do not favor the use of these sterols as markers of cholesterol absorption. This bears direct consequences for the interpretation of earlier studies, as well as for future studies targeting intestinal regulation of cholesterol metabolism.
Jakulj, Lily; Mohammed, Hussein; van Dijk, Theo H.; Boer, Theo; Turner, Scott; Groen, Albert K.; Vissers, Maud N.; Stroes, Erik S. G.
Similar serum plant sterol responses of human subjects heterozygous for a mutation causing sitosterolemia and controls to diets enriched in plant sterols or stanols
Objective:We investigated the serum phytosterol responses of heterozygous relatives of sitosterolemia patients to diets enriched in phytosterols or stanols.Design:Randomized double-blind crossover design.Setting:Muenster, Germany.Subjects:Eight heterozygous and 13 control subjects were recruited. One heterozygote and three controls dropped out.Interventions:Seven heterozygotes and 10 controls received daily portions of margarine containing 2 g of plant sterols, 2 g of stanols or a control margarine
M Kratz; F Kannenberg; E Gramenz; B Berning; E Trautwein; G Assmann; S Rust
Effect of plant sterols and tannins on Phytophthora ramorum growth and sporulation.
Elicitin-mediated acquisition of plant sterols is required for growth and sporulation of Phytophthora spp. This study examined the interactions between elicitins, sterols, and tannins. Ground leaf tissue, sterols, and tannin-enriched extracts were obtained from three different plant species (California bay laurel, California black oak, and Oregon white oak) in order to evaluate the effect of differing sterol/tannin contents on Phytophthora ramorum growth. For all three species, high levels of foliage inhibited P. ramorum growth and sporulation, with a steeper concentration dependence for the two oak samples. Phytophthora ramorum growth and sporulation were inhibited by either phytosterols or tannin-enriched extracts. High levels of sterols diminished elicitin gene expression in P. ramorum; whereas the tannin-enriched extract decreased the amount of 'functional' or ELISA-detectable elicitin, but not gene expression. Across all treatment combinations, P. ramorum growth and sporulation correlated strongly with the amount of ELISA-detectable elicitin (R (2)?= 0.791 and 0.961, respectively). PMID:23689874
Stong, Rachel A; Kolodny, Eli; Kelsey, Rick G; González-Hernández, M P; Vivanco, Jorge M; Manter, Daniel K
Sterol binding by methyl-?-cyclodextrin and nystatin--comparative analysis of biochemical and physiological consequences for plants.
The dependence of membrane function on its sterol component has been intensively studied with model lipids and isolated animal membranes, but to a much lesser extent with plant membranes. Depleting membrane sterols could be predicted to have a strong effect on membrane activity and have harmful physiological consequences. In this study, we characterized membrane lipid composition, membrane permeability for ions, some physiological parameters, such as H2O2 accumulation, formation of autophagosomal vacuoles, and expression of peroxidase and autophagic genes, and cell viability in the roots of wheat (Triticum aestivum L.) seedlings in the presence of two agents that specifically bind to endogenous sterols. The polyene antibiotic nystatin binds to endogenous sterols, forming so-called 'nystatin pores' or 'channels' in the membrane, and methyl-?-cyclodextrin has the capacity to sequester sterols in its hydrophobic core. Unexpectedly, although application of both methyl-?-cyclodextrin and nystatin reduced the sterol content, their effects on membrane permeability, oxidative status and autophagosome formation in roots differed dramatically. For comparison, we also tested the effects of the antibiotic gramicidin S, which does not bind to sterols but forms nonspecific channels in the membrane. Gramicidin S considerably increased membrane permeability, caused oxidative stress, and reduced cell viability. Our results suggest that a decrease in the sterol content is, in itself, not sufficient to have deleterious effects on a cell. The disturbance of membrane integrity, rather than the decrease in the sterol content, is responsible for the toxicity of sterol-binding compounds. PMID:24612537
Valitova, Julia; Sulkarnayeva, Albina; Kotlova, Ekaterina; Ponomareva, Anastasia; Mukhitova, Fakhima K; Murtazina, Lyaisan; Ryzhkina, Irina; Beckett, Richard; Minibayeva, Farida
Differential modulation of membrane structure and fluctuations by plant sterols and cholesterol.
We have studied the concentration and temperature dependent influence of cholesterol, stigmasterol, and sitosterol on the global structure and the bending fluctuations of fluid dimyristoyl phosphatidylcholine and palmitoyl oleoyl phosphatidylcholine bilayers applying small-angle x-ray scattering, as well as dilatometry and ultrasound velocimetry. Independent of the lipid matrix, cholesterol was found to be most efficient in modulating bilayer thickness and elasticity, followed by sitosterol and stigmasterol. This can be attributed to the additional ethyl groups and double bond at the C(17) alkyl side-chain of the two plant sterols. Hence, it seems that some flexibility of the sterol hydrocarbon chain is needed to accommodate within the lipid bilayer. In addition, we did not observe two populations of membranes within the putative liquid-ordered/liquid-disordered phase coexistence regime of binary sterol/lipid mixtures. Instead, the diffraction patterns could be interpreted in terms of a uniform phase. This lends further support to the idea of compositional fluctuations of unstable sterol rich domains recently brought up by fluorescence microscopy experiments, which contrasts the formation of stable domains within the miscibility gap of binary lipid/sterol mixtures. PMID:18234811
Hodzic, Aden; Rappolt, Michael; Amenitsch, Heinz; Laggner, Peter; Pabst, Georg
Differential Modulation of Membrane Structure and Fluctuations by Plant Sterols and Cholesterol
We have studied the concentration and temperature dependent influence of cholesterol, stigmasterol, and sitosterol on the global structure and the bending fluctuations of fluid dimyristoyl phosphatidylcholine and palmitoyl oleoyl phosphatidylcholine bilayers applying small-angle x-ray scattering, as well as dilatometry and ultrasound velocimetry. Independent of the lipid matrix, cholesterol was found to be most efficient in modulating bilayer thickness and elasticity, followed by sitosterol and stigmasterol. This can be attributed to the additional ethyl groups and double bond at the C17 alkyl side-chain of the two plant sterols. Hence, it seems that some flexibility of the sterol hydrocarbon chain is needed to accommodate within the lipid bilayer. In addition, we did not observe two populations of membranes within the putative liquid-ordered/liquid-disordered phase coexistence regime of binary sterol/lipid mixtures. Instead, the diffraction patterns could be interpreted in terms of a uniform phase. This lends further support to the idea of compositional fluctuations of unstable sterol rich domains recently brought up by fluorescence microscopy experiments, which contrasts the formation of stable domains within the miscibility gap of binary lipid/sterol mixtures.
Hodzic, Aden; Rappolt, Michael; Amenitsch, Heinz; Laggner, Peter; Pabst, Georg
Synthesis of Hydroxylated Sterols in Transgenic Arabidopsis Plants Alters Growth and Steroid Metabolism1[C][W][OA
To explore mechanisms in plant sterol homeostasis, we have here increased the turnover of sterols in Arabidopsis (Arabidopsis thaliana) and potato (Solanum tuberosum) plants by overexpressing four mouse cDNA encoding cholesterol hydroxylases (CHs), hydroxylating cholesterol at the C-7, C-24, C-25, or C-27 positions. Compared to the wild type, the four types of Arabidopsis transformant showed varying degrees of phenotypic alteration, the strongest one being in CH25 lines, which were dark-green dwarfs resembling brassinosteroid-related mutants. Gas chromatography-mass spectrometry analysis of extracts from wild-type Arabidopsis plants revealed trace levels of ? and ? forms of 7-hydroxycholesterol, 7-hydroxycampesterol, and 7-hydroxysitosterol. The expected hydroxycholesterol metabolites in CH7-, CH24-, and CH25 transformants were identified and quantified using gas chromatography-mass spectrometry. Additional hydroxysterol forms were also observed, particularly in CH25 plants. In CH24 and CH25 lines, but not in CH7 ones, the presence of hydroxysterols was correlated with a considerable alteration of the sterol profile and an increased sterol methyltransferase activity in microsomes. Moreover, CH25 lines contained clearly reduced levels of brassinosteroids, and displayed an enhanced drought tolerance. Equivalent transformations of potato plants with the CH25 construct increased hydroxysterol levels, but without the concomitant alteration of growth and sterol profiles observed in Arabidopsis. The results suggest that an increased hydroxylation of cholesterol and/or other sterols in Arabidopsis triggers compensatory processes, acting to maintain sterols at adequate levels.
Beste, Lisa; Nahar, Nurun; Dalman, Kerstin; Fujioka, Shozo; Jonsson, Lisbeth; Dutta, Paresh C.; Sitbon, Folke
Differential effects on inhibition of cholesterol absorption by plant stanol and plant sterol esters in apoE-/- mice
Aims 'Functional foods' supplemented with plant sterol esters (PSE) and plant stanol esters (PSA) are therapeutic options for the management of hypercholesterolaemia. However, their effects on blood monocytes, endothelial function, atherogenesis, and sterol tissue concentrations are poorly understood. Methods and results Male apoE?/? mice (n= 30) were randomized to three different diets for 6 weeks (n= 10 per group): high-cholesterol (1.25%) western-type diet (WTD), WTD + 2% PSE, and WTD + 2% PSA. Both supplements reduced serum cholesterol. WTD + PSE resulted in increased plant sterol serum concentrations and increased inflammatory Ly-6C(high) monocyte numbers. WTD + PSA increased plant stanol serum concentrations and Ly-6C-monocyte numbers, but decreased vascular superoxide release, lipid hydroperoxides, and inflammatory cytokines in aortic tissue, in plasma, and in circulating monocytes. Despite reduced serum cholesterol concentrations, both supplements impaired endothelial vasodilation compared with WTD. WTD + PSA reduced the development of atherosclerotic lesions compared with WTD alone (12.7 ± 3.7 vs. 28.3 ± 3.5%), and WTD + PSE was less effective (17.5 ± 3.7%). WTD + PSE and WTD + PSA reduced the cholesterol content in the liver, but not in the brain. However, WTD + PSE and WTD + PSA increased plant sterol and plant stanol concentrations in the liver as well as in the brain. Conclusion PSE and PSA supplementation reduced serum cholesterol, but increased plant sterol and plant stanol concentrations. Elevated levels of PSE and PSA were associated with endothelial dysfunction and increased central nervous system depositions. Atherosclerotic lesion retardation was more pronounced in WTD + PSA, coinciding with higher regenerative monocyte numbers, decreased oxidative stress, and decreased inflammatory cytokines compared with WTD + PSE.
Weingartner, Oliver; Ulrich, Christof; Lutjohann, Dieter; Ismail, Kenan; Schirmer, Stephan H.; Vanmierlo, Tim; Bohm, Michael; Laufs, Ulrich
Elicitins trap and transfer sterols from micelles, liposomes and plant plasma membranes
Using elicitins, proteins secreted by some phytopathogenic Oomycetes (Phytophthora) known to be able to transfer sterols between phospholipid vesicles, the transfer of sterols between micelles, liposomes and biological membranes was studied. Firstly, a simple fluorometric method to screen the sterol-carrier capacity of proteins, avoiding the preparation of sterol-containing phospholipidic vesicles, is proposed. The transfer of sterols between DHE micelles (donor)
Sébastien Vauthrin; Vladimir Mikes; Marie-Louise Milat; Michel Ponchet; Bernard Maume; Hanan Osman; Jean-Pierre Blein
21 CFR 101.83 - Health claims: plant sterol/stanol esters and risk of coronary heart disease (CHD).
Preferential campesterol incorporation into various tissues in apolipoprotein E*3-Leiden mice consuming plant sterols or stanols.
Intestinal absorption of plant sterols and stanols is much lower as compared with that of cholesterol; and therefore, serum concentrations are low. Circulating plant sterols and stanols are incorporated into tissues. However, hardly any data are available about tissue distributions of individual plant sterols and stanols, particularly in relation to their serum concentrations. We therefore fed female apolipoprotein E*3-Leiden mice a control diet, a plant sterol-enriched diet (1g/100 g diet), or a plant stanol-enriched diet (1g/100 g diet) for 8 weeks. In the sterol group, serum cholesterol-standardized campesterol and sitosterol concentrations were, respectively, 8 and 7 times higher as compared with those in the control group. Consequently, the serum campesterol-sitosterol ratio remained essentially unchanged. Cholesterol-standardized plant sterol concentrations increased significantly in all analyzed tissues, except brain. However, the campesterol-sitosterol ratio also increased in all tissues (except in liver and spleen), suggesting that campesterol is preferentially incorporated over sitosterol in those tissues. For the stanol group, serum plant stanol concentrations also increased; but the increase was but less pronounced. We conclude that, in apolipoprotein E*3-Leiden mice, campesterol is preferentially incorporated into most tissues over sitosterol, which cannot be deduced from changes in serum concentrations. PMID:18702950
Plat, Jogchum; de Jong, Arienne; Volger, Oscar L; Princen, Hans M G; Mensink, Ronald P
The cholesterol-lowering effect of plant sterol-containing beverage in hypercholesterolemic subjects with low cholesterol intake
We investigated the effect of a beverage containing plant sterols on serum concentrations of triacylglycerol and cholesterol of hypercholesterolemic subjects that consume a low cholesterol diet. Fifty three hypercholesterolemic subjects (fasting LDL-cholesterol > 130 mg\\/dl) were fed a placebo beverage for 4 weeks followed by feeding a test beverage containing plant sterols for 8 weeks in a single-blind, randomized cross-over
Min-Jeong Shin; Se-Joong Rim; Yangsoo Jang; Donghoon Choi; Seok-Min Kang; Seung-Yun Cho; Sung-Soon Kim; Dong Kee Kim; Kijun Song; Namsik Chung
The ABCG8 G574R Variant, Serum Plant Sterol Levels, and Cardiovascular Disease Risk in the Old Order Amish
Objective To determine whether long-term exposure to moderate elevations in plasma plant sterol levels increases risk for atherosclerosis. Methods and Results In Old Order Amish participants aged 18 to 85 years, with (n=110) and without (n=181) 1 copy of the ABCG8 G574R variant, we compared mean plasma levels of plant sterols and cholesterol precursors and carotid intima-media wall thickness. Carriers of a single 574R allele had increased plant sterol levels (eg, 35%–37% higher plasma levels of sitosterol, campesterol, and stigmasterol) and increased plant sterol/cholesterol ratios (P<0.001 for all). 574R carriers had significantly decreased levels of lathosterol and lanosterol, precursors in a pathway for endogenous cholesterol synthesis, suggesting that plant sterols may alter regulation of genes involved in cholesterol synthesis. The G574R variant was not associated with high-density lipoprotein cholesterol or low-density lipoprotein cholesterol levels. Compared with noncarriers, 574R carriers had decreased carotid intima-media wall thickness (0.62 versus 0.66 mm; age- and sex-adjusted P=0.03). Adjustment for body weight, blood pressure, and standard lipid measures (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides) did not alter this association. Conclusion Although the G574R variant is associated with moderately elevated plant sterol levels, carriers of the 574R allele had modestly lower levels of carotid wall thickness compared with noncarriers.
Horenstein, Richard B.; Mitchell, Braxton D.; Post, Wendy S.; Lutjohann, Dieter; von Bergmann, Klaus; Ryan, Kathleen A.; Terrin, Michael; Shuldiner, Alan R.; Steinle, Nanette I.
Effect of plant sterols, fatty acids and lecithin on cholesterol absorption in vivo in the rat
The inhibitory effect of plant sterols, fatty acids and lecithin on cholesterol intestnal absorption was studied in the unanesthetized\\u000a rat using a single pass perfusion technique. Bile was excluded from the perfused intestine. Cholesterol absorption did not\\u000a change following the additions of cholestanol, cholestanone, lanosterol, stigmasterol and ?-sitosterol. A 3-fold increase\\u000a in the molarity of cholestanol and ?-sitosterol or the
Daniel Hollander; Donna Morgan
Sterol transporters: targets of natural sterols and new lipid lowering drugs.
Recent insights in the role of ATP-binding cassette (ABC) transporters ABCG5 and ABCG8, the discovery of ezetimibe, the first approved direct cholesterol absorption inhibitor, as well as the identification of Niemann-Pick C1 Like 1 (NPC1L1) protein as sterol transporter in the gut, focused attention on sterol transport processes in the small intestine and the liver. The identification of defective structures in the ABCG5 or ABCG8 transporters in patients with the rare disease of sitosterolemia elucidated their role as sterol efflux pumps regulating at least in parts the intestinal sterol absorption and the hepatic sterol output. ABCG5 and ABCG8 themselves are regulated by cholesterol via liver X receptors (LXRs), which are also activated by oxysterols and some derivatives of plant sterols. NPC1L1 could recently be identified as a major sterol transporter for the intestinal uptake of cholesterol as well as plant sterols. Studies in NPC1L1 knockout mice indicate that this transporter is essential for the intestinal uptake of sterols and that NPC1L1 might also be involved in the mechanism of action of ezetimibe. However, studies with photoreactive cholesterol as well as with photoreactive ezetimibe analogues suggest that other processes might also be involved in the mechanism of action of ezetimibe. PMID:15737409
Sudhop, Thomas; Lütjohann, Dieter; von Bergmann, Klaus
Reduced-calorie orange juice beverage with plant sterols lowers C-reactive protein concentrations and improves the lipid profile in
Background: Dietary plant sterols effectively reduce LDL choles- terol when incorporated into fat matrices. We showed previously that supplementation with orange juice containing plant sterols (2 g\\/d) significantly reduced LDL cholesterol. Inflammation is pivotal inatherosclerosis.High-sensitivityC-reactiveprotein(hs-CRP),the prototypic marker of inflammation, is a cardiovascular disease risk marker; however, there is a paucity of data on the effect of plant sterols on CRP
Sridevi Devaraj; Bryce C Autret; Ishwarlal Jialal
Lowering LDL cholesterol with margarine containing plant stanol/sterol esters: is it still relevant in 2011?
Recommendations about the use of plant stanol/sterol esters have not been updated since 2001. There have been many developments in medicines for lipid-lowering since 2001. In this review, the use of margarines containing stanol or sterol esters, to lower LDL cholesterol is considered in the 2011 setting. Firstly, there is a brief overview of the effects of the stanols/sterols on LDL cholesterol, which shows that these agents have a modest ability to lower LDL cholesterol, and are not effective in all conditions. Secondly, the relevance of the stanols/sterols in 2010/1 is questioned, given they have not been shown to reduce clinical endpoints, and have no effects on HDL cholesterol or triglyceride levels. Finally, there is a section comparing the stanols/sterols with the present day prescription lipid lowering medicines. Prescription drugs (statins, ezetimibe, and niacin) have a much greater ability to lower LDL cholesterol than the stanol/sterol esters, and also increase levels of HDL cholesterol and decrease levels of triglycerides. The statins and niacin have been shown to reduce cardiovascular clinical endpoints. Except in borderline normo/hypercholesterolemia, prescription drugs should be preferred to stanol/sterol esters for lowering LDL cholesterol in 2011. PMID:21296266
Doggrell, Sheila Anne
Role of membrane sterols and cortical microtubules in gravity resistance in plants
NASA Astrophysics Data System (ADS)
Resistance to the gravitational force is a principal graviresponse in plants comparable to gravitropism Nevertheless only limited information has been obtained for this graviresponse We have examined mechanisms of signal perception transformation and transduction of the perceived signal and response to the transduced signal in gravity resistance using hypergravity conditions produced by centrifugation In Arabidopsis hypocotyls hypergravity treatment greatly increased the expression level of 3-hydroxy-3-methylglutaryl-Coenzyme A reductase HMGR which catalyzes a reaction producing mevalonic acid a key precursor of terpenoids such as membrane sterols Geranyl diphosphate synthase gene was also up-regulated by hypergravity whereas the expression of other genes involved in membrane lipid metabolism was not influenced Hypergravity caused an increase in sterol content in azuki bean epicotyls but not in phospholipid glycolipid or fatty acid content Also hypergravity did not influence fatty acid composition in any lipid class Thus the effect of hypergravity on membrane lipid metabolism was specific for sterol synthesis On the other hand alpha- and beta-tubulin genes were up-regulated by hypergravity treatment in Arabidopsis hypocotyls Hypergravity also induced reorientation of cortical microtubules in azuki epicotyls the percentage of epidermal cells with transverse microtubles was decreased whereas that with longitudinal microtubules was increased Inhibitors of HMGR action and microtubule-disrupting agents completely prevented the gravity resistance
Hoson, T.; Koizumi, T.; Matsumoto, S.; Kumasaki, S.; Soga, K.; Wakabayashi, K.; Sakaki, T.
Involvement of membrane sterols in hypergravity-induced modifications of growth and cell wall metabolism in plant stems
NASA Astrophysics Data System (ADS)
Organisms living on land resist the gravitational force by constructing a tough body Plants have developed gravity resistance responses after having first went ashore more than 500 million years ago The mechanisms of gravity resistance responses have been studied under hypergravity conditions which are easily produced on earth by centrifugation In Arabidopsis hypocotyls hypergravity treatment greatly increased the expression level of 3-hydroxy-3-methylglutaryl-Coenzyme A reductase HMGR which is involved in synthesis of terpenoids such as membrane sterols In the present study we examined the role of membrane sterols in gravity resistance in plants by analyzing sterol levels of stem organs grown under hypergravity conditions and by analyzing responses to hypergravity of the organs whose sterol level was modulated Hypergravity inhibited elongation growth but stimulated lateral expansion of Arabidopsis hypocotyls and azuki bean epicotyls Under hypergravity conditions sterol levels were kept high as compared with 1 g controls during incubation Lovastatin an inhibitor HMGR prevented lateral expansion as the gravity resistance response in azuki bean epicotyls Similar results were obtained in analyses with loss of function mutants of HMGR in Arabidopsis It has been shown that sterols play a role in cellulose biosynthesis probably as the primer In wild type Arabidopsis hypocotyls hypergravity increased the cellulose content but it did not influence the content in HMGR mutants These results suggest that hypergravity increases
Koizumi, T.; Soga, K.; Wakabayashi, K.; Suzuki, M.; Muranaka, T.; Hoson, T.
Plant sterol and stanol intake in Finland: a comparison between users and nonusers of plant sterol- and plant stanol-enriched foods.
Background/ Objectives:We evaluated plant sterol and stanol (PS) intakes from natural sources and enriched foods in the Finnish population-based national FINDIET 2007 Survey. In addition, we compared the users and nonusers of PS-enriched foods in terms of their characteristics and dietary intake.Subjects/Methods:This was a cross-sectional population-based study on 958 men and 1080 women aged 25-74. Users and nonusers of PS-enriched products were compared with respect to sex, age, education, region, cholesterol-lowering medication and cholesterol-lowering diet. Intakes of PS, energy, energy nutrients, fat composition, cholesterol and dietary fibre were calculated on the basis of a 48-h dietary recall. The distribution of PS intake was assessed for the users of enriched products.Results:PS-enriched foods were used by 9.5% of all subjects. The usage increased significantly with age (P<0.001) and level of education (P=0.01). The usage of enriched products was more common among those following a cholesterol-lowering medication or diet (P<0.001 for both). Among users, the mean intake of PS was 2.2?g/d for men and 1.6?g/d for women, and among nonusers it was 363?mg/d for men and 286?mg/d for women. The majority of users received less than 2?g/d of PS from enrichment, but 20% of users obtained more than 3?g of PS per day.Conclusions:The intake of PS can reach several grams in a subgroup of subjects consuming PS-enriched foods. The manufacturers' recommendations on PS-enriched food consumption are not consistently followed, and customer guidance needs to be improved. PMID:24518750
Marttinen, M; Kosola, M; Ovaskainen, M-L; Mutanen, M; Männistö, S
Cholesterol-lowering effects of plant sterol esters and non-esterified stanols in margarine, butter and low-fat foods
Objectives: To determine the efficacy on plasma cholesterol-lowering of plant sterol esters or non-esterified stanols eaten within low-fat foods as well as margarine.Design: Randomised, controlled, single-blind study with sterol esters and non-esterified plant stanols provided in breakfast cereal, bread and spreads. Study 1 comprised 12 weeks during which sterol esters (2.4 g) and stanol (2.4 g) -containing foods were eaten
P Nestel; M Cehun; S Pomeroy; M Abbey; G Weldon
The Metabolic Effects of Omega3 Plant Sterol Esters in Mixed Hyperlipidemic Subjects
Purpose The aim of the current study was to evaluate the therapeutic effects of omega-3 plant sterol esters (n-3-PSE) on lipid profile\\u000a and other coronary heart disease risk factors in subjects with mixed hyperlipidemia.\\u000a \\u000a \\u000a \\u000a \\u000a Methods Ninety-one patients with mixed hyperlipidemia were randomized in a double blind fashion to receive either placebo (corn oil)\\u000a or n-3-PSE. Twenty four patients dropped out or were
Rafael Bitzur; Hofit Cohen; Tzafra Cohen; Tali W. Dror; Yael Herzog; Yael Lifshitz; Tamar Lubish; Dror Harats; Ardon Rubinstein
Effects of long term plant sterol and -stanol consumption on the retinal vasculature: a randomized controlled trial in statin users.
As sitosterolemic patients have an increased cardiovascular risk, there is concern that reducing serum LDL-cholesterol concentrations by plant sterols enriched functional foods might adversely affect vascular function. Whether increased concentrations of plant sterols truly affect vascular function and whether these effects are exclusive to the larger vessels remains unknown. We compared the effects of long-term plant sterol and -stanol consumption on changes in retinal vessels diameter which reflex alterations in the microcirculation. Three randomized groups were studied at baseline and after 85-weeks. Group one (N=11) consumed plant sterol enriched margarine (2.5g/day), the second (N=8) plant stanol enriched margarine (2.5g/day), and the control group (N=11) non-enriched margarine (2.5g/day). Serum cholesterol-standardized campesterol and sitosterol concentrations increased by 354.84±168.22·102?mol/mmol and 84.36±48.26·102?mol/mmol (p<0.001), respectively in the sterol group, while decreasing non-significantly in the plant stanol group. Serum LDL-cholesterol concentrations decreased significantly in both the plant sterol (-0.33±0.33mmol/L, p=0.016) and -stanol groups (-0.38±0.34mmol/L, p=0.018) compared to the increase in the controls (0.29±0.34mmol/L). The mean change in venular diameters for the plant sterol group (2.3±3.1?m), plant stanol groups (-0.8±3.4?m) and control group (-0.8±5.1?m) did not reach significance but the change in cholesterol-standardized campesterol concentrations correlated positively with the change in venular diameter independent of changes in serum LDL-cholesterol concentrations (r=0.39, N=30, p=0.033). Increased serum campesterol concentration correlated positively with increased retinal venular diameter, independent from changes in serum LDL-cholesterol concentrations. This may constitute an explanation for the suggested effects of plant sterols on vascular function. However, this novel finding needs confirmation and further study. PMID:21122856
Kelly, Elton R; Plat, Jogchum; Mensink, Ronald P; Berendschot, Tos T J M
Mycoplasma lactucae sp. nov., a sterol-requiring mollicute from a plant surface.
Strain 831-C4T (T = type strain), isolated from the surface of lettuce plants (Lactuca sativa) obtained from a retail food market, was shown to be a sterol-requiring mollicute. Morphological examination of this organism by electron and dark-field microscopic techniques showed that it consists of small, nonhelical, nonmotile, pleomorphic coccoid cells, with individual cells surrounded by a single cytoplasmic membrane. No evidence of a cell wall was observed. The organism grew rapidly in all conventional culture medium formulations for mollicutes in either aerobic or anaerobic environments. The optimum temperature for growth was 30 degrees C, but multiplication occurred at 18 to 37 degrees C. Strain 831-C4T catabolized glucose, but hydrolysis of arginine or urea could not be demonstrated. The genome size of strain 831-C4T was determined to be about 569 megadaltons, while the base composition (guanine-plus-cytosine content) of the DNA was 30.0 mol%. Recent studies in which we compared the 16S rRNA sequences of strain 831-C4T with those of more than 40 other mollicutes indicated that this organism is phylogenetically related to the Spiroplasma-Mycoplasma mycoides clade. Strain 831-C4T was serologically unrelated to the type strains of previously described Mycoplasma species and to 18 other unclassified sterol-requiring isolates cultivated from various animal, plant, or insect sources. Strain 831-C4T (= ATCC 49193) is the type strain of Mycoplasma lactucae sp. nov. PMID:2223606
Rose, D L; Kocka, J P; Somerson, N L; Tully, J G; Whitcomb, R F; Carle, P; Bové, J M; Colflesh, D E; Williamson, D L
Metabolism of conjugated sterols in eggplant. Part 1. UDP-glucose : sterol glucosyltransferase
A membrane-bound UDP-glucose : sterol glucosyltransferase from Solanum melongena (eggplant) leaves was partially purified and its specificity as well as molecular and kinetic properties were defined. Among a wide spectrum of 3-OH steroids (i.e. typical plant sterols, androstane, pregnane and cholestane derivatives, steroidal alkaloids and sapogenins) and triterpenic alcohols, the high- est activity was found with 22-oxycholesterol. UDP-glucose appeared to
Anna Potocka; Jan Zimowski
Long-term consumption of plant stanol and sterol esters, vascular function and genetic regulation.
Polymorphisms of the ABCG5 and ABCG8 genes interfere with cholesterol absorption and synthesis. We determined whether common polymorphisms of these genes regulate the responses of serum cholesterol and vascular function during long-term inhibition of cholesterol absorption. Mildly to moderately hypercholesterolaemic subjects (n 282) completed a 1-year study consuming plant stanol or sterol ester (2 g stanol or sterol) or control spread. Serum cholesterol and non-cholesterol sterols, markers of cholesterol absorption and synthesis, and variables of vascular function and structure were analysed in relation to common polymorphisms of ABCG5 and ABCG8. At baseline, subjects with the 54K allele of ABCG8 had higher brachial endothelial-dependent flow-mediated dilatation than those without it (5.79 (se 0.31) v. 4.46 (se 0.44) %; P = 0.049), and subjects with the 632V allele of ABCG8 had larger brachial artery diameter than those without it. Polymorphisms of ABCG5 and ABCG8 were neither associated with serum cholesterol reduction nor changes in cholesterol metabolism or in vascular function. However, in subjects with the 400K allele of ABCG8, intima media thickness (IMT) was increased in all groups more than in those without it (P < 0.05). In conclusion, serum cholesterol lowering with absorption inhibition was not associated with polymorphic sites of ABCG5 and ABCG8. However, regulation of baseline cholesterol metabolism and vascular function and structure, and IMT progression during 1 year seemed to share some of the common polymorphic sites of these genes, suggesting a gene-regulated interaction between cholesterol metabolism and vascular function and structure. PMID:19019257
Gylling, Helena; Hallikainen, Maarit; Raitakari, Olli T; Laakso, Markku; Vartiainen, Erkki; Salo, Pia; Korpelainen, Vesa; Sundvall, Jouko; Miettinen, Tatu A
Sterol composition of mycelia of the plant pathogenic ascomycete Leptosphaeria maculans.
Analysis of sterols in mycelia of the ascomycete, Leptosphaeria maculans by gas chromatography-mass spectrometry revealed that ergosterol comprised 95% of the total sterols, with eight other sterols comprising the remaining 5%. Six of these latter sterols were putative precursors of ergosterol and their presence suggested a pathway for ergosterol biosynthesis in this fungus. Ergosterol biosynthesis in fungi is inhibited by the triazole antifungal agent flutriafol. When L. maculans was grown in the presence of flutriafol, ergosterol content decreased while two 14 alpha-methylated sterols, 24-methylene dihydrolanosterol and obtusifoliol, accumulated. PMID:12482449
Griffiths, K M; Bacic, A; Howlett, B J
Phospholipid-Dependence of Plant UDP-Glucose Sterol ?-d-Glucosyl Transferase 1
The phospholipid dependence of the UDP-glucose sterol glucosyl transferase (UDPG-SGTase) from maize coleoptiles was previously demonstrated using the partially purified and highly delipidated enzyme, in the presence of the detergent Triton X-100 (P Ullmann, P Bouvier-Navé, P Benveniste [1987] Plant Physiol 85: 51-55). We now report the reconstitution of the enzyme activity into unilamellar lipid vesicles. This was achieved by adding phospholipids, sterols and ?-octylglucoside to the solubilized enzyme and passing the mixture through Sephadex G-50. The treatment led to almost complete removal of the detergents. The incorporation of UDPG-SGTase in the lipid vesicles was demonstrated by (a) coelution of the enzyme activity with the labeled lipid vesicles (average diameter: 260Ĺ) on a Sephacryl S-1000 column and (b) flotation experiments on metrizamide density gradients. Release of dithiobis-(2-nitro-benzoic acid) (DTNB) from DTNB-preloaded vesicles was very slow, indicating good membrane integrity of the vesicles. Treatment of the intact vesicles with the nonpermeant reagent p-chloro-mercuribenzene sulfonate led to more than 95% inactivation of the total enzyme activity, i.e. the activity measured in the presence of Triton X-100 at permeabilizing concentration. This suggests an outward orientation for the active site of the enzyme. Finally, the enzyme was incorporated into vesicles of various phospholipid compositions and the kinetic parameters of the reactions were determined. Our results clearly show that the reconstituted UDPG-SGTase activity is stimulated to a large extent by negatively charged phospholipids.
Ury, Alain; Benveniste, Pierre; Bouvier-Nave, Pierrette
Pigmented rice bran and plant sterol combination reduces serum lipids in overweight and obese adults.
Objective: This study investigated the dietary effect of including pigmented rice bran with or without plant sterols on lipid profiles during energy restriction-induced weight loss in overweight and obese adults not taking cholesterol-lowering medication. In addition, the study examined the effect of intervention on biomarkers of oxidative stress and inflammation. Methods: A group of 24 overweight and obese adults (age: 43 ± 6 years, body mass index 32 ± 1 kg/m(2), 18 females) were randomized to a 25% calorie-restricted diet containing either pigmented rice bran (RB) or the RB with addition of plant sterols (RB+PS) snack bars for 8 weeks. The individualized nutrient-balanced diet contained ?70% of daily energy needs assessed from indirect calorimetry measured resting energy expenditure (EE) and physical activity-related EE assessed using accelerometry. Anthropometrics, blood pressure, blood lipids, glucose, urinary F2-isoprostanes, C-reactive protein, insulin, and leptin were measured at baseline and after 8 weeks of intervention. Results: Participants lost approximately 4.7 ± 2.2 kg (p < 0.001). Weight loss was not significant between the RB+PS and RB group (p = 0.056). Changes in body fat corresponded to changes in body weight. Average decrease in total cholesterol was significantly higher in the RB+PS group than in the RB group (difference 36 ± 25 g/dL vs 7 ± 16 g/dL; p = 0.044). A similar pattern was observed for the decrease in low-density lipoprotein (LDL) cholesterol (difference 22.3 ± 25.2 g/dL vs 4.4 ± 18.9 g/dL; p = 0.062). Changes in systolic blood pressure, serum levels of leptin, and F2-isoprostanes were significant between baseline values and after 8 weeks on the diet in both groups (p < 0.05) but did not differ between the 2 groups. Conclusions: A nutrient-balanced and energy-restricted diet supplemented with rice bran and plant sterols resulted in a significant decrease in total and LDL cholesterol in overweight and obese adults. PMID:24955613
Hongu, Nobuko; Kitts, David D; Zawistowski, Jerzy; Dossett, Cynthia M; Kope?, Aneta; Pope, Benjamin T; Buchowski, Maciej S
Sterol-dependent induction of plant defense responses by a microbe-associated molecular pattern from Trichoderma viride.
Plant-microbe interactions involve numerous regulatory systems essential for plant defense against pathogens. An ethylene-inducing xylanase (Eix) of Trichoderma viride is a potent elicitor of plant defense responses in specific cultivars of tobacco (Nicotiana tabacum) and tomato (Solanum lycopersicum). We demonstrate that tomato cyclopropyl isomerase (SlCPI), an enzyme involved in sterol biosynthesis, interacts with the LeEix2 receptor. Moreover, we examined the role of SlCPI in signaling during the LeEix/Eix defense response. We found that SlCPI is an important factor in the regulation of the induction of defense responses such as the hypersensitive response, ethylene biosynthesis, and the induction of pathogenesis-related protein expression in the case of LeEix/Eix. Our results also suggest that changes in the sterol composition reduce LeEix internalization, thereby attenuating the induction of plant defense responses. PMID:24351686
Sharfman, Miya; Bar, Maya; Schuster, Silvia; Leibman, Meirav; Avni, Adi
Dietary intake of naturally occurring plant sterols is related to a lower risk of a first myocardial infarction in men but not in women in northern Sweden.
Dietary intake of naturally occurring plant sterols is inversely related to serum cholesterol concentrations. Elevated serum cholesterol increases the risk of myocardial infarction (MI), but it is unknown if this can be reduced by dietary intake of naturally occurring plant sterols. Our aim was to investigate if a high intake of naturally occurring plant sterols is related to a lower risk of contracting a first MI. The analysis included 1005 prospective cases (219 women, 786 men) and 3148 matched referents (723 women, 2425 men), aged 29-73 y at baseline, from the population-based Northern Sweden Health and Disease Study. A food frequency questionnaire (FFQ) was completed at baseline. Absolute plant sterol intake was inversely related to the risk of a first MI in men (OR highest vs. lowest quartile = 0.70; 95% CI: 0.53, 0.85; P-trend = 0.006) but not in women. After adjustment for confounders, the estimated risk was somewhat attenuated (OR highest vs. lowest quartile = 0.71; 95% CI: 0.55, 0.92; P-trend = 0.067), suggesting that increasing sterol intake from 150 to 340 mg/d reduces the risk of a first MI by 29%. Energy-adjusted plant sterol intake was not related to the risk of a first MI in either men or women. In conclusion, the findings of this observational study show that a high absolute intake of naturally occurring plant sterols is significantly related to a lower risk of a first MI in men in northern Sweden, whereas no significant relation was seen for energy-adjusted plant sterol intake. In women, no significant associations were found. The results from this study show that intake of plant sterols may be important in prevention of MI. PMID:23925940
Klingberg, Sofia; Ellegĺrd, Lars; Johansson, Ingegerd; Jansson, Jan-Hĺkan; Hallmans, Göran; Winkvist, Anna
Cholesterol and plant sterol efflux from cultured intestinal epithelial cells is mediated by ATP-binding cassette transporters.
In this study we analyzed functions of ATP-binding cassette (ABC) transporters involved in sterol transport from Caco-2 cells. Treatment with a synthetic liver x receptor ligand elevated both mRNA and protein levels of ABCG5, G8, and ABCA1. The ligand stimulated cholesterol efflux, suggesting that ABC transporters are involved in it. To identify the acceptors of cholesterol, potential molecules such as apolipoprotein A-I, glycocholic acid, phosphatidylcholine, and bile acid micelles were added to the medium. Apo A-I, a known acceptor of cholesterol transported by ABCA1, elevated cholesterol efflux on the basal side, whereas the others raised cholesterol efflux on the apical side. Moreover, bile acid micelles preferentially augmented plant sterol efflux rather than cholesterol. Finally, in HEK293 cells stably expressing ABCG5/G8, bile acid micelle-mediated sterol efflux was significantly accelerated. These results indicate that ABCG5/G8, unlike ABCA1, together with bile acids should participate in sterol efflux on the apical surface of Caco-2 cells. PMID:17690481
Tachibana, Shizuko; Hirano, Maki; Hirata, Takashi; Matsuo, Michinori; Ikeda, Ikuo; Ueda, Kazumitsu; Sato, Ryuichiro
Impact of atorvastatin and omega-3 ethyl esters 90 on plasma plant sterol concentrations and cholesterol synthesis in type 2 diabetes: A randomised placebo controlled factorial trial
ObjectiveTo determine the effects of statin treatment and omega-3 polyunsaturated fatty acid supplementation on plasma plant sterol concentrations and cholesterol synthesis in patients with type 2 diabetes.
H. A. W. Neil; U. Ceglarek; J. Thiery; S. Paul; A. Farmer; R. R. Holman
Dose-response effects of different plant sterol sources in fat spreads on serum lipids and C-reactive protein and on the kinetic behavior of serum plant sterols
Objective:To test the dose-response effect on low-density lipoprotein cholesterol (LDL-c) of plant sterols (PS) from different sources in a low-fat spread.Methods:Dose responses of soybean oil (BO), tall oil (TO) and a mix of tall oil and rapeseed oil (TO\\/RP) as fatty acid esters were tested in a parallel design in free-living subjects recruited from the general community who had elevated
P M Clifton; M Mano; G S M J E Duchateau; H C M van der Knaap; E A Trautwein
Loci on chromosomes 14 and 2, distinct from ABCG5\\/ABCG8, regulate plasma plant sterol levels in a C57BL\\/6J × CASA\\/Rk intercross
Plasma plant sterol levels differ among humans due to genetic and dietary factors. A disease characterized by high plasma plant sterol levels, -sitosterolemia, was recently found to be due to mutations at the ABCG5\\/ABCG8 locus. To detect variants at this and other loci, a genetic cross was carried out between two laboratory mouse strains. Parental C57BL\\/6J had almost twice the
Ephraim Sehayek; Elizabeth M. Duncan; Dieter Lutjohann; Klaus von Bergmann; Jennie G. Ono; Ashok K. Batta; Gerald Salen; Jan L. Breslow
Soy Protein Enhances the Cholesterol-Lowering Effect of Plant Sterol Esters in Cholesterol-Fed Hamsters1
This study aimed to investigate whether the combination of plant sterol esters (PSE) with soy protein or soy isoflavones may have extra cholesterol-lowering effects. Male hamsters (n 20\\/group) were fed diets containing (g\\/100 g diet) (A) 20 casein (control), (B) 0.24 PSE, (C) 20 intact soy protein (replacing casein), (D) 0.02 soy isoflavones, (E) 0.24 PSE plus 20 soy protein
Yuguang Lin; Gert W. Meijer; Mario A. Vermeer; Elke A. Trautwein
Plant sterols-enriched diet decreases small, dense LDL-cholesterol levels in children with hypercholesterolemia: a prospective study
Background Small dense low density lipoprotein-cholesterol (sdLDL-C) molecules are more atherogenic compared with large buoyant ones. Phytosterols-enriched diets are effective in decreasing total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) concentrations in hyperlipidemic children without significant adverse effects. Limited data on the impact of such a diet on sdLDL-C levels is available in adults while there are no reports concerning children. The purpose of this study is to prospectively evaluate the effect of the daily consumption of 2 g of plant sterols on sdLDL-C levels in children with hypercholesterolemia. Methods Fifty-nine children, 25 with LDL-C???3.4 mmol/l (130 mg/dl) and 34 with LDL-C?3.4 mmol/l, aged 4.5-15.9 years, were included in the study. A yogurt-drink enriched with 2 g of plant sterols was added to the daily diet of hypercholesterolemic children and 6–12 months later lipid profiles were reassessed. Direct quantitative methods were used to measure LDL-C and sdLDL-C levels. Results The consumption of plant sterols reduced sdLDL-C significantly (p?0.001), but levels remained higher compared with controls (p?0.001). TC, LDL-C, non high density lipoprotein-cholesterol (NonHDL-C) and apolipoprotein B (ApoB) levels also decreased significantly (p?0.05). The median reduction of sdLDL-C and LDL-C was 16.6% and 13%, respectively. These variables decreased >10% in sixteen children (64%), independently from baseline levels, sex, age and body mass index (BMI). High density lipoprotein-cholesterol (HDL-C), lipoprotein a [Lp(a)], and triglycerides (TGs) levels remained unaffected. Conclusions Plant sterols decrease sdLDL-C significantly and may be beneficial for children with hypercholesterolemia.
Sterol requirement of Mycoplasma capricolum.
Mycoplasmas require an external source of sterol for growth. For Mycoplasma capricolum this requirement is met not only by cholesterol but also by the methylcholestane derivatives lanosterol, cycloartenol, 4,4-dimethylcholesterol, and 4beta-methylcholestanol. Cholesteryl methyl ether and 3alpha-methylcholestanol serve equally well as sterol supplements. None of the growth-supporting sterol derivatives tested was metabolically modified. The unusual acceptance of diverse cholestane derivatives by a mycoplasma species contrasts with the structural attributes thought to be necessary for sterol function in eukaryotic membranes.
Odriozola, J M; Waitzkin, E; Smith, T L; Bloch, K
LDL-cholesterol-lowering effect of plant sterols and stanols across different dose ranges: a meta-analysis of randomised controlled studies.
Phytosterols (PS, comprising plant sterols and plant stanols) have been proven to lower LDL-cholesterol concentrations. The dose-response relationship for this effect has been evaluated in several meta-analyses by calculating averages for different dose ranges or by applying continuous dose-response functions. Both approaches have advantages and disadvantages. So far, the calculation of averages for different dose ranges has not been done for plant sterols and stanols separately. The objective of the present meta-analysis was to investigate the combined and separate effects of plant sterols and stanols when classified into different dose ranges. Studies were searched and selected based on predefined criteria. Relevant data were extracted. Average LDL-cholesterol effects were calculated when studies were categorised by dose, according to random-effects models while using the variance as weighing factor. This was done for plant sterols and stanols combined and separately. In total, 124 studies (201 strata) were included. Plant sterols and stanols were administered in 129 and fifty-nine strata, respectively; the remaining used a mix of both. The average PS dose was 2·1 (range 0·2-9·0) g/d. PS intakes of 0·6-3·3 g/d were found to gradually reduce LDL-cholesterol concentrations by, on average, 6-12 %. When plant sterols and stanols were analysed separately, clear and comparable dose-response relationships were observed. Studies carried out with PS doses exceeding 4 g/d were not pooled, as these were scarce and scattered across a wide range of doses. In conclusion, the LDL-cholesterol-lowering effect of both plant sterols and stanols continues to increase up to intakes of approximately 3 g/d to an average effect of 12 %. PMID:24780090
Ras, Rouyanne T; Geleijnse, Johanna M; Trautwein, Elke A
Sterols of the fungi - Distribution and biosynthesis.
NASA Technical Reports Server (NTRS)
The importance of sterols in the growth and reproduction in fungi is becoming increasingly apparent. This article concerns the composition and biosynthesis of ergosterol in these organisms. Comparison to plant and animal sterol formation are made.
Weete, J. D.
Consuming functional foods enriched with plant sterol or stanol esters for 85 weeks does not affect neurocognitive functioning or mood in statin-treated hypercholesterolemic individuals.
Recent animal and human studies have shown that plant sterols and stanols, which are used as functional food ingredients to lower increased LDL cholesterol concentrations, pass the blood-brain barrier. Whether this affects neurocognitive functioning and mental well-being in humans has, to our knowledge, never been investigated. The aim of the present study was therefore to examine the effects of long-term plant sterol or stanol consumption on neurocognitive functioning and mood in a randomized, double-blind, placebo-controlled dietary intervention trial. To this end, hypercholesterolemic individuals, aged 43-69 y, receiving stable statin treatment were randomly assigned to an 85-wk supplementation with margarines enriched with plant sterol esters (2.5 g/d), plant stanol esters (2.5 g/d), or placebo. At baseline and at the end of the intervention period, all participants underwent a cognitive assessment. In addition, subjective cognitive functioning and mood were assessed by means of questionnaires (Cognitive Failure Questionnaire and depression subscale of the Symptom Checklist 90, respectively). Long-term supplementation with plant sterol or stanol esters did not affect cognitive performance (memory, simple information processing speed, complex information processing speed, Letter-Digit Substitution test performance), subjective cognitive functioning, or mood. In conclusion, the present results indicate that long-term use of plant sterols or stanols at recommended intakes of 2.5 g/d does not affect neurocognitive functioning or mood in hypercholesterolemic individuals receiving statin treatment. PMID:19458031
Schiepers, Olga J G; de Groot, Renate H M; van Boxtel, Martin P J; Jolles, Jelle; de Jong, Ariënne; Lütjohann, Dieter; Plat, Jogchum; Mensink, Ronald P
Sterols of a contemporary lacustrine sediment. [in English postglacial lake
NASA Technical Reports Server (NTRS)
Results are reported for detailed sterol analyses of several depths (corresponding to between zero and about 150 yr in age) in a contemporary lacustrine sediment from a freshwater lake of postglacial origin in England. Delta 5-, delta 22-, and delta 5,22-sterols are identified along with 5 alpha- and 5 beta-stanols as well as a C26 stanol with a C7 side chain. Solvent extraction yields carbon number distributions for the 5 alpha- and 5 beta-stanol sediment constituents that parallel the corresponding delta 5-sterol distributions. The amounts of 5 alpha-stanols are found to exceed those of 5 beta-stanols in the sediment, and variations in the ratio of 5 alpha- to 5 beta-stanol between sediment samples from similar depths are shown to suggest an inhomogeneity of the sediment. It is found that the sterol composition of sediment cores varies markedly with depth, reflecting both the effects of a sterol hydrogenation process and a changing input to the sediment. It is concluded that C29 sterols, of probable higher-plant origin, predominate at lower sediment depths while C27 sterols, possibly derived from autochthonous sources, are more abundant in the surface sediment.
Gaskell, S. J.; Eglinton, G.
Increased plasma plant sterol levels in heterozygotes with sitosterolemia and xanthomatosis
Plasma sterol levels in a family of sitosterolemia and xanthomatosis were determined by a high performance liquid chromatography. Three affected siblings manifested marked xanthomatosis including subcutaneous soft tissues and general- ized atherosclerosis. Two other siblings as well as children of the patients did not show such clinical symptoms and signs. Plasma levels of cholesterol, sitosterol, campesterol, and cholestanol in three
Hideki Hidaka; Takaaki Nakamura; Takahiko Aoki; Hideto Kojima; Yuzuru Nakajima; Keisuke Kosugi; Ikuo Hatanaka; Masaki Harada; Masashi Kobayashi; Akira Tamura; Tatsuzo Fujii; Yukio Shigeta
Effects of long-term plant sterol or stanol ester consumption on lipid and lipoprotein metabolism in subjects on statin treatment.
Consumption of plant sterol- or stanol-enriched margarines by statin users results in an additional LDL-cholesterol reduction of approximately 10 %, which may be larger than the average decrease of 3-7 % achieved by doubling the statin dose. However, whether this effect persists in the long term is not known. Therefore, we examined in patients already on stable statin treatment the effects of 85 weeks of plant sterol and stanol ester consumption on the serum lipoprotein profile, cholesterol metabolism, and bile acid synthesis. For this, a double-blind randomised trial was designed in which fifty-four patients consumed a control margarine with no added plant sterols or stanols for 5 weeks (run-in period). For the next 85 weeks, seventeen subjects continued with the control margarine and the other two groups with either a plant sterol (n 18) or plant stanol (n 19) (2.5 g/d each) ester-enriched margarine. Blood was sampled at the end of the run-in period and every 20 weeks during the intervention period. Compared with the control group, plant sterol and stanol ester consumption reduced LDL-cholesterol by 0.28 mmol/l (or 8.7 %; P = 0.08) and 0.42 mmol/l (13.1 %; P = 0.006) respectively after 85 weeks. No effects were found on plasma concentrations of oxysterols or 7 alpha-hydroxy-4-cholesten-3-one, a bile acid synthesis marker. We conclude that long-term consumption of both plant sterol and stanol esters effectively lowered LDL-cholesterol concentrations in statin users. PMID:18846701
de Jong, Ariënne; Plat, Jogchum; Lütjohann, Dieter; Mensink, Ronald P
A comparative calorimetric study of the effects of cholesterol and the plant sterols campesterol and brassicasterol on the thermotropic phase behavior of dipalmitoylphosphatidylcholine bilayer membranes.
We present a comparative differential scanning calorimetric study of the effects of the animal sterol cholesterol (Chol) and the plant sterols campesterol (Camp) and brassicasterol (Bras) on the thermotropic phase behavior of dipalmitoylphosphatidylcholine (DPPC) bilayers. Camp and Bras differ from Chol in having a C24 methyl group and, additionally for Bras, a C22 trans-double bond. Camp and especially Bras decrease the temperature, cooperativity and enthalpy of the DPPC pretransition more than Chol, although these effects are attenuated at higher sterol levels. This indicates that they destabilize gel-state DPPC bilayers to a greater extent, but are less soluble, than Chol. Not surprisingly, all three sterols have similar effects on the sterol-poor sharp component of the DPPC main phase transition. However, Camp and especially Bras less effectively increase the temperature and decrease the cooperativity and enthalpy of the broad component of the main transition than Chol. This indicates that at higher sterol concentrations, Camp and Bras are less miscible and less effective than Chol at ordering the hydrocarbon chains of the sterol-enriched fluid DPPC bilayers. Overall, these alkyl side chain modifications generally reduce the ability of Chol to produce its characteristic effects on DPPC bilayer physical properties. These differences are likely due to the less extended and more bent conformations of the alkyl side chains of Camp and Bras, producing sterols with a greater effective cross-sectional area and reduced length than Chol. Hence, the structure of Chol is likely optimized for maximum solubility in, as opposed to maximum ordering of, phospholipid bilayers. PMID:24704414
Benesch, Matthew G K; McElhaney, Ronald N
Cholesterol-lowering effects of plant sterol esters differ in milk, yoghurt, bread and cereal
Objective: To measure the relative effects of each of four phytosterol ester-enriched low-fat foods (bread, breakfast cereal, milk and yoghurt) on serum lipids, plasma phytosterols and carotenoids.Design: Three research centres undertook a randomised, incomplete crossover, single-blind study consisting of four treatment periods of 3 weeks each, one of which was a control period. Each sterol-enriched test food provided 1.6 g\\/day
P M Clifton; M Noakes; D Sullivan; N Erichsen; D Ross; G Annison; A Fassoulakis; M Cehun; P Nestel
Brassinosteroid/Sterol synthesis and plant growth as affected by lka and lkb mutations of Pea
The dwarf pea (Pisum sativum) mutants lka and lkb are brassinosteroid (BR) insensitive and deficient, respectively. The dwarf phenotype of the lkb mutant was rescued to wild type by exogenous application of brassinolide and its biosynthetic precursors. Gas chromatography-mass spectrometry analysis of the endogenous sterols in this mutant revealed that it accumulates 24-methylenecholesterol and isofucosterol but is deficient in their hydrogenated products, campesterol and sitosterol. Feeding experiments using 2H-labeled 24-methylenecholesterol indicated that the lkb mutant is unable to isomerize and/or reduce the Delta24(28) double bond. Dwarfism of the lkb mutant is, therefore, due to BR deficiency caused by blocked synthesis of campesterol from 24-methylenecholesterol. The lkb mutation also disrupted sterol composition of the membranes, which, in contrast to those of the wild type, contained isofucosterol as the major sterol and lacked stigmasterol. The lka mutant was not BR deficient, because it accumulated castasterone. Like some gibberellin-insensitive dwarf mutants, overproduction of castasterone in the lka mutant may be ascribed to the lack of a feedback control mechanism due to impaired perception/signal transduction of BRs. The possibility that castasterone is a biologically active BR is discussed. PMID:10198111
Nomura; Kitasaka; Takatsuto; Reid; Fukami; Yokota
Long-term plant stanol and sterol ester-enriched functional food consumption, serum lutein/zeaxanthin concentration and macular pigment optical density.
Observational epidemiological studies have shown that low carotenoid intake and/or low carotenoid blood levels increase the risk of degenerative diseases like age-related macular degeneration. Functional foods enriched with plant sterol or stanol esters may lower serum concentrations of fat-soluble carotenoids. Theoretically, as a result the macular pigment optical density (MPOD), a marker for eye health, may change. We carried out a double-blind placebo-controlled human intervention trial with a duration of 18 months to evaluate the possible effects of plant stanol and sterol esters on serum lutein/zeaxanthin concentration in relation to the MPOD. Forty-seven subjects were randomly assigned to one of the three treatment groups: margarine without added plant sterols or stanols, plant sterol-enriched margarine, or plant stanol-enriched margarine. Serum cholesterol and lutein/zeaxanthine concentrations and the MPOD were evaluated at baseline and at study end. Changes in lipid-adjusted serum lutein/zeaxanthine concentrations between baseline and study end differed significantly between the three groups (P = 0.001). We found no differences in the MPOD between the three treatment groups, despite the differences in both absolute and cholesterol-standardized serum lutein/zeaxanthine concentrations. This shows that the observed reduction in serum carotenoid concentrations during 18 months consumption of these functional foods does not affect MPOD. PMID:18986598
Berendschot, Tos T J M; Plat, Jogchum; de Jong, Ariënne; Mensink, Ronald P
Cloning, functional expression and phylogenetic analysis of plant sterol 24C-methyltransferases involved in sitosterol biosynthesis.
Sterol 24C-methyltransferases (SMTs) constitute a group of sequence-related proteins that catalyze the distinct patterns of 24-alkyl sterols that occur throughout nature. Two SMT cDNAs (SMT2-1 and SMT2-2) were cloned by homology based PCR methods from young leaves of Glycine max (soybean) and the corresponding enzymes were expressed functionally in Escherichia coli. The full-length cDNA for SMT2-1 and SMT2-2 have open reading frames of 1086 bp and 1092 bp, respectively, and encode proteins of 361 and 363 residues with a calculated molecular mass of 40.3 and 40.4 kDa, respectively. The substrate preference of the two isoforms was similar yet they differed from SMT1; kinetically SMT2-1 and SMT2-2 generated k(cat) values for the optimal substrate 24(28)methylene lophenol of 0.8 min(-1) and 1.34 min(-1), respectively, compared to the activity of SMT1 that generated a k(cat) for the optimal substrate cycloartenol of 0.6 min(-1). SMT2-2 was purified to homogeneity and the subunit organization shown to be tetrameric in similar fashion to other cloned SMTs. Analysis of the accumulated products catalyzed by the recombinant enzymes demonstrated that soybean SMT2-1 and SMT2-2 operate transalkylation activities analogous to the soybean plant SMT1. Metabolite analyses correlated with transcript profiling of the three SMT isoforms during soybean maturation clearly demonstrated that SMT isoform expression determines specific C24-methyl to C24-ethyl ratios to flowering whereas with seed development there is a disconnection such that the SMT transcript levels decrease against an increase in sterol content; generally SMT2-2 is expressed more than SMT2-1 or SMT1. These observations suggest that the genes that encode SMT1 and SMT2 in sitosterol biosynthesis may have undergone divergent evolution. In support of this proposition, the genomic organization for SMT1 of fungi and protozoa align very closely with one another and to those of the plant SMT2; both sets of SMTs lack introns. Unexpectedly, the SMT1 from Glycine max and other embryophytes of diverse origin possess disparate intron-exon characteristics that can be shown relates back to the algae. Our results suggest that the order of SMT1 appearing before SMT2 in phytosterol synthesis arose recently in plant evolution in response to duplication of a more primitive SMT gene likely to have been bifunctional and catalytically promiscuous. PMID:19818974
Neelakandan, Anjanasree K; Song, Zhihong; Wang, Junqing; Richards, Matthew H; Wu, Xiaolei; Valliyodan, Babu; Nguyen, Henry T; Nes, W David
Key points for maximum effectiveness and safety for cholesterol-lowering properties of plant sterols and use in the treatment of metabolic syndrome.
According to the American Diabetes Association and the Adult Treatment Panel III, the starting point for treating metabolic syndrome (MS) is a change of lifestyle. In addition, action on the main symptoms of MS by means of dietary supplements, can be helpful in view of the chronic course of the disease. The term 'phytosterols' refers to sterols and stanols composed of lipophilic triterpenes, a family that is widely distributed in the plant kingdom and whose cholesterol-lowering properties have been amply demonstrated. In the light of the recent literature, the key points for maximum effectiveness and safety of sterols are the following. (A) Plant sterols should be taken with meals: clinical trials have shown that when plant sterols are consumed close to mealtimes, low-density lipoprotein cholesterol may decrease by 9.4%, while when they are taken between meals, the reduction is about 6%. (B) The optimal dosage is 2-2.5 g day(-1) in a single dose. More than 3 g day(-1) has not been found to have any additional beneficial effect and increases the risk of side effects. (C) The food matrix used to dissolve the phytosterols should contain a certain amount of fat. A milk-based matrix appears optimal from this point of view. © 2013 Society of Chemical Industry. PMID:23584958
Rondanelli, Mariangela; Monteferrario, Francesca; Faliva, Milena Anna; Perna, Simone; Antoniello, Neldo
A dietary portfolio approach to cholesterol reduction: combined effects of plant sterols, vegetable proteins, and viscous fibers in hypercholesterolemia.
Plant sterols, soy proteins, and viscous fibers are advised for cholesterol reduction but their combined effect has never been tested. We therefore assessed their combined effect on blood lipids in hyperlipidemic subjects who were already consuming a low-saturated fat, low-cholesterol diet before starting the study. The test (combination) diet was 1 month in duration and was very low in saturated fat and high in plant sterols (1 g/1,000 kcal), soy protein (23 g/1,000 kcal), and viscous fibers (9 g/1,000 kcal) obtained from foods available in supermarkets and health food stores. One subject also completed 2 further diet periods: a low-fat control diet and a control diet plus 20 mg/d lovastatin. Fasting blood lipids, blood pressure, and body weight were measured prior to and at weekly intervals during the study. The combination diet was rated as acceptable and very filling. The diet reduced low-density lipoprotein (LDL)-cholesterol by 29.0% +/- 2.7% (P <.001) and the ratio of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol by 26.5% +/- 3.4% (P <.001). Near maximal reductions were seen by week 2. In the subject who took Mevacor and control diets each for 4 weeks, the reduction in LDL:HDL-cholesterol on Mevacor was similar to the combination diet. We conclude that acceptable diets of foods from supermarkets and health food stores that contain recognized cholesterol-lowering dietary components in combination (a dietary portfolio) may be as effective as the starting dose of older first-line drugs in managing hypercholesterolemia. PMID:12489074
Jenkins, David J A; Kendall, Cyril W C; Faulkner, Dorothea; Vidgen, Edward; Trautwein, Elke A; Parker, Tina L; Marchie, Augustine; Koumbridis, George; Lapsley, Karen G; Josse, Robert G; Leiter, Lawrence A; Connelly, Philip W
Combined effects of a dietary portfolio of plant sterols, vegetable protein, viscous fibre and almonds on LDL particle size.
Studies conducted in the last 20 years have led to the identification of small dense LDL as an important risk factor for CVD. Consumption of plant sterols, soyabean proteins, viscous fibre and nuts are known to modulate the risk of CVD favourably through their cholesterol (Chol)-lowering properties, both independently and more recently in combination. Nevertheless, their combined impact on the LDL particle size phenotype has never been tested. In the present study, we assessed the effect of incorporating concurrently plant sterols (1 g/4.2 MJ), soyabean protein (23 g/4.2 MJ), viscous fibre (9 g/4.2 MJ) and almonds (15 g/4.2 MJ) into a diet very low in saturated fat in twelve patients with mildly elevated plasma LDL-Chol levels. Fasting blood lipids were obtained at the start of the study and at 2-week intervals during the 4-week study. The diet-induced reduction in plasma LDL-Chol of 30.0 (se 3.0) % (P<0.0001) was attributed to concurrent reductions in the serum Chol concentrations of large (>26.0 nm-30 (se 8) %, P<0.001), medium (25.5-26.0 nm-29 (se 3) %, P<0.001) and small (<25.5 nm-21 (sd 6) %, P<0.01) LDL particles, with near maximal reductions seen by week 2. These results indicate that foods and dietary components advocated for their potential to reduce the risk of CVD are effective in reducing serum concentrations of all LDL fractions including small dense LDL, thus potentially further contributing to an overall lower risk of CVD. PMID:15522135
Lamarche, Benoît; Desroches, Sophie; Jenkins, David J A; Kendall, Cyril W C; Marchie, Augustine; Faulkner, Dorothea; Vidgen, Edward; Lapsley, Karen G; Trautwein, Elke A; Parker, Tina L; Josse, Robert G; Leiter, Lawrence A; Connelly, Philip W
A different function for a member of an ancient and highly conserved cytochrome P450 family: From essential sterols to plant defense
CYP51 sterol demethylases are the only cytochrome P450 enzymes with a conserved function across the animal, fungal, and plant kingdoms (in the synthesis of essential sterols). These highly conserved enzymes, which are important targets for cholesterol-lowering drugs, antifungal agents, and herbicides, are regarded as the most ancient member cytochrome P450 family. Here we present a report of a CYP51 enzyme that has acquired a different function. We show that the plant enzyme AsCYP51H10 is dispensable for synthesis of essential sterols and has been recruited for the production of antimicrobial compounds (avenacins) that confer disease resistance in oats. The AsCyp51H10 gene is synonymous with Sad2, a gene that we previously had defined by mutation as being required for avenacin synthesis. In earlier work, we showed that Sad1, the gene encoding the first committed enzyme in the avenacin pathway (?-amyrin synthase), had arisen by duplication and divergence of a cycloartenol synthase-like gene. Together these data indicate an intimate evolutionary connection between the sterol and avenacin pathways. Sad1 and Sad2 lie within 70 kb of each other and are expressed specifically in the epidermal cells of the root tip, the site of accumulation of avenacins. These findings raise intriguing questions about the recruitment, coevolution, and regulation of the components of this specialized defense-related metabolic pathway.
Qi, Xiaoquan; Bakht, Saleha; Qin, Bo; Leggett, Mike; Hemmings, Andrew; Mellon, Fred; Eagles, John; Werck-Reichhart, Daniele; Schaller, Hubert; Lesot, Agnes; Melton, Rachel; Osbourn, Anne
Lamellar self-assemblies of single-chain amphiphiles and sterols and their derived liposomes: distinct compositions and distinct properties.
Typically, single-chain amphiphiles and sterols do not form fluid lamellar phases once hydrated individually. Most of the single-chain amphiphiles form actually micelles in aqueous environments, while sterols display a very limited solubility in water. However, under certain conditions, mixtures of single-chain amphiphiles and sterols lead to the formation of stable fluid bilayers. Over the past decade, several of these systems leading to fluid lamellar self-assemblies have been identified and this article reviews the current knowledge relative to these non-phospholipid bilayers made of single-chain amphiphiles and sterols. It presents an integrated view about the molecular features that are required for their stability, the properties they share, and the origin of these characteristics. It was also shown that these lamellar systems could lead to the formation of unilamellar vesicles, similar to phospholipid based liposomes. These vesicles display distinct properties that make them potentially appealing for technological applications; they display a limited permeability, they are stable, they are formed with molecules that are relatively chemically inert (and relatively cheap), and they can be readily functionalized. The features of these distinct liposomes and their technological applications are reviewed. Finally, the putative biological implications of these non-phospholipid fluid bilayers are also discussed. PMID:24184913
Cui, Zhong-Kai; Lafleur, Michel
Increased plasma plant sterol concentrations and a heterozygous amino acid exchange in ATP binding cassette transporter ABCG5: a case report.
Whilst conducting a scientific study, an elevated plasma plant sterol concentration of 3.07 mg/dL was established in one proband. Similar levels found in his mothers plasma (2.73 mg/dL) were suggestive of a heterozygous sitosterolemia. The resulting gene analysis for ATP binding cassette transporter G5/G8 (ABCG5/G8) revealed a heterozygous polymorphism in ABCG8 (Thr400Lys, rs4148217), which the proband had inherited from his father. However, a heterozygous amino acid exchange (Arg406Gln) in exon 9 of ABCG5 was revealed, which was inherited from his mother. Although not sufficient evidence exists to regard this sequence variation as a mutation, this previously unreleased sequence variation occurred in a "hot spot" area for sitosterolemia of the ABCG5 gene (exon 9) and the similar increased plasma plant sterol concentrations of the heterozygous mother contribute to the notion, that this very likely presents an inactivating mutation. PMID:21664501
Keller, Sylvia; Prechtl, Danielle; Aslanidis, Charalampos; Ceglarek, Uta; Thiery, Joachim; Schmitz, Gerd; Jahreis, Gerhard
The Cholesterol-Lowering Action of Plant Stanol Esters
Plant sterols and stanols derived from wood pulp and vegetable oils lower total and LDL cholesterol by inhibiting cholesterol absorption from the intestine in hu- mans. Plant stanols are virtually unabsorbable, which makes them more ideal hypocholesterolemic agents than plant sterols. The esterification of plant stanols has allowed their incorporation into various foods such as margarine without changing the taste
Tu T. Nguyen
A Combination of Psyllium and Plant Sterols Alters Lipoprotein Metabolism in Hypercholesterolemic Subjects by Modifying the Intravascular Processing of Lipoproteins and Increasing LDL Uptake1,2
We previouslydemonstrated that a diet therapy involving consumption of 7.28g psyllium (PSY) and 2 g of plant sterols (PS) per day reduced LDL cholesterol from 3.6 6 0.7 to 3.1 6 0.8 mmol\\/L (P , 0.01) and decreased the number of intermediate density lipoprotein particles and the smaller LDL and HDL subfractions in hypercholesterolemic individuals (n Ľ 33). The study
Sudeep Shrestha; Hedley C. Freake; Mary M. McGrane; Jeff S. Volek; Maria Luz Fernandez
Increased plasma plant sterol concentrations and a heterozygous amino acid exchange in ATP binding cassette transporter ABCG5: A case report
Whilst conducting a scientific study, an elevated plasma plant sterol concentration of 3.07 mg\\/dL was established in one proband. Similar levels found in his mothers plasma (2.73 mg\\/dL) were suggestive of a heterozygous sitosterolemia. The resulting gene analysis for ATP binding cassette transporter G5\\/G8 (ABCG5\\/G8) revealed a heterozygous polymorphism in ABCG8 (Thr400Lys, rs4148217), which the proband had inherited from his father. However,
Sylvia Keller; Danielle Prechtl; Charalampos Aslanidis; Uta Ceglarek; Joachim Thiery; Gerd Schmitz; Gerhard Jahreis
The plant sterol guggulsterone attenuates inflammation and immune dysfunction in murine models of inflammatory bowel disease.
Inflammatory bowel diseases (IBD) are chronic inflammatory and relapsing diseases of the gut that may manifest as either Crohn's disease (CD) or ulcerative colitis (UC). CD and UC are immunologically different diseases characterized by exacerbated Th1 and Th2 response. T-cell resistance against apoptosis contributes to inappropriate T-cell accumulation and the perpetuation of chronic mucosal inflammation. In the present study we have investigated the effect exerted by guggulsterone (GS) a plant derived steroid isolated from the gum resin of the Commiphora mukul tree, in two models of intestinal inflammation induced in mice by trinitro-benzene sulfonic acid (TNBS) and oxazolone. We provided evidence that E-GS protects mice against development of sign and symptoms of colon inflammation. E-GS effectively attenuated the severity of wasting disease and the fecal score and colon inflammation as assessed by measuring the macroscopic- and microscopic-damage scores. Administration Z-GS failed to ameliorate colon inflammation in TNBS-induced colitis and had a partial effect in oxazolone-induced colitis. In vitro, mechanistic studies carried out using CD4+ cells isolated from the intestinal lamina propria demonstrate that GS effectively regulates the function of effector T cells by modulating cell signaling activation pathway caused by CD3/CD28. The net biological effects resulting from exposure to GS includes attenuation of generation of interleukin-2 and -4 and interferon-gamma as well as T cell proliferation. In conclusion, GS is an anti-inflammatory compound with the capacity to prevent and ameliorate T-cell-induced colitis. These data ground the use of GS, a natural cholesterol-lowering agent, in the treatment of chronic inflammatory diseases. PMID:19555671
Mencarelli, Andrea; Renga, Barbara; Palladino, Giuseppe; Distrutti, Eleonora; Fiorucci, Stefano
Arabidopsis Sterol Endocytosis Involves Actin-Mediated Trafficking via ARA6Positive Early Endosomes
Background: In contrast to the intense attention devoted to research on intracellular sterol trafficking in animal cells, knowledge about sterol transport in plant cells remains limited, and virtually nothing is known about plant endocytic sterol trafficking. Similar to animals, biosynthetic sterol transport occurs from the endoplasmic reticulum (ER) via the Golgi apparatus to the plasma membrane. The vesicle trafficking inhibitor
Markus Grebe; Jian Xu; Wiebke Möbius; Takashi Ueda; Akihiko Nakano; Hans J. Geuze; Martin B. Rook; B. J. G. Scheres
The hydroxyanilide fenhexamid, a new sterol biosynthesis inhibitor fungicide efficient against the plant pathogenic fungus Botryotinia fuckeliana (Botrytis cinerea).
Fenhexamid, a recently developed botryticide, is shown here to inhibit sterol biosynthesis. When the fungus Botryotinia fuckeliana was grown in the presence of fenhexamid, the ergosterol content was reduced, and three 3-keto compounds, 4 alpha-methylfecosterone, fecosterone and episterone, accumulated, suggesting an inhibition of the 3-keto reductase involved in C-4 demethylation. Thus, fenhexamid belongs to a new, promising class of sterol biosynthesis inhibitors not previously used in agriculture or in medicine. PMID:11721524
Debieu, D; Bach, J; Hugon, M; Malosse, C; Leroux, P
Evaluating potential applications of faecal sterols in distinguishing sources of faecal contamination from mixed faecal samples.
Faecal samples from humans, herbivores, carnivores and birds as well as samples from septic tanks and effluents from a sewage treatment plant (STP) were extracted and analyzed by gas chromatography-mass spectrometry for faecal sterols including coprostanol, epicoprostanol, cholestanol, cholesterol, stigmasterol, campesterol, 24-ethylcoprostanol and beta-sitosterol. Coprostanol was observed in the highest concentrations from the human derived samples, but it was also present in substantial quantities in a range of herbivores. There was no unique marker of human faecal contamination. Multivariate analyses revealed that the faecal sterol profiles were significantly different between the four groups of animals (Wilks' lambda=0.007, P<0.002), and coprostanol and 24-ethylcoprostanol were the major discriminant factors. However, when faecal samples were mixed, the confounding of faecal sterol levels prevented accurate identification of contributing species. Conversely, faecal sterol ratios were highly efficient at identifying which mixtures contained human contribution, but could not appropriately determine percentage contributions of sources. PMID:17614115
Shah, Vikaskumar G; Dunstan, R Hugh; Geary, Phillip M; Coombes, Peter; Roberts, Timothy K; Von Nagy-Felsobuki, Ellak
The sterol methyltransferases SMT1, SMT2, and SMT3 influence Arabidopsis development through nonbrassinosteroid products.
Plant sterols are structural components of cell membranes that provide rigidity, permeability, and regional identity to membranes. Sterols are also the precursors to the brassinosteroid signaling molecules. Evidence is accumulating that specific sterols have roles in pattern formation during development. COTYLEDON VASCULAR PATTERNING1 (CVP1) encodes C-24 STEROL METHYLTRANSFERASE2 (SMT2), one of three SMTs in Arabidopsis (Arabidopsis thaliana). SMT2 and SMT3, which also encodes a C-24 SMT, catalyze the reaction that distinguishes the synthesis of structural sterols from signaling brassinosteroid derivatives and are highly regulated. The deficiency of SMT2 in the cvp1 mutant results in moderate developmental defects, including aberrant cotyledon vein patterning, serrated floral organs, and reduced stature, but plants are viable, suggesting that SMT3 activity can substitute for the loss of SMT2. To test the distinct developmental roles of SMT2 and SMT3, we identified a transcript null smt3 mutant. Although smt3 single mutants appear wild type, cvp1 smt3 double mutants show enhanced defects relative to cvp1 mutants, such as discontinuous cotyledon vein pattern, and produce novel phenotypes, including defective root growth, loss of apical dominance, sterility, and homeotic floral transformations. These phenotypes are correlated with major alterations in the profiles of specific sterols but without significant alterations to brassinosteroid profiles. The alterations to sterol profiles in cvp1 mutants affect auxin response, demonstrated by weak auxin insensitivity, enhanced axr1 auxin resistance, ectopically expressed DR5:beta-glucuronidase in developing embryos, and defective response to auxin-inhibited PIN2-green fluorescent protein endocytosis. We discuss the developmental roles of sterols implied by these results. PMID:20421456
Carland, Francine; Fujioka, Shozo; Nelson, Timothy
Effects on the human serum lipoprotein profile of beta-glucan, soy protein and isoflavones, plant sterols and stanols, garlic and tocotrienols.
The effects of beta-glucan, soy protein, isoflavones, plant sterols and stanols, garlic and tocotrienols on serum lipoproteins have been of great interest the last decade. From a critical review of the literature, it appeared that recent studies found positive as well as no effects of beta-glucan from oats on serum LDL cholesterol concentrations. These conflicting results may suggest that the cholesterol-lowering activity of products rich in oat beta-glucan depends on factors, such as its viscosity in the gastrointestinal tract, the food matrix and/or food processing. The effects of beta-glucan from barley or yeast on the lipoprotein profile are promising, but more human trials are needed to further substantiate these effects. It is still not clear whether the claimed hypocholesterolemic effects of soy can be attributed solely to the isoflavones. Several studies found no changes in serum LDL cholesterol concentrations after consumption of isolated soy isoflavones (without soy protein), indicating that a combination of soy protein and isoflavones may be needed for eliciting a cholesterol-lowering effect of soy. Therefore, the exact (combination of) active ingredients in soy products need to be identified. The daily consumption of 2-3 g of plant sterols or stanols reduces LDL cholesterol concentrations by 9-14%. It has been demonstrated that functional foods enriched with plant sterols and stanols are effective in various population groups, and in combination with cholesterol-lowering diets or drugs. Whether garlic or garlic preparations can be used as a lipid-lowering agent is still uncertain. It is important to characterize the active components in garlic and their bioavailability after ingestion. It is not very likely that tocotrienols from palm oil or rice bran oil have favorable effects on the human serum lipoprotein profile. PMID:12221200
Kerckhoffs, Daniëlle A J M; Brouns, Fred; Hornstra, Gerard; Mensink, Ronald P
Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study
Background Assessment of cardiovascular disease (CVD) risk factors can predict clinical manifestations of atherosclerosis in adulthood. In this pilot study with hypercholesterolemic children and adolescents, we investigated the effects of a combination of plant sterols, fish oil and B vitamins on the levels of four independent risk factors for CVD; LDL-cholesterol, triacylglycerols, C-reactive protein and homocysteine. Methods Twenty five participants (mean age 16 y, BMI 23 kg/m2) received daily for a period of 16 weeks an emulsified preparation comprising plant sterols esters (1300 mg), fish oil (providing 1000 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA)) and vitamins B12 (50 ?g), B6 (2.5 mg), folic acid (800 ?g) and coenzyme Q10 (3 mg). Atherogenic and inflammatory risk factors, plasma lipophilic vitamins, provitamins and fatty acids were measured at baseline, week 8 and 16. Results The serum total cholesterol, LDL- cholesterol, VLDL-cholesterol, subfractions LDL-2, IDL-1, IDL-2 and plasma homocysteine levels were significantly reduced at the end of the intervention period (p<0.05). The triacylglycerols levels decreased by 17.6%, but did not reach significance. No significant changes in high sensitivity C-reactive protein, HDL-cholesterol and apolipoprotein A-1 were observed during the study period. After standardisation for LDL cholesterol, there were no significant changes in the levels of plasma ?-tocopherol, ?-carotene and retinol, except for reduction in ?-tocopherol levels. The plasma levels of n-3 fatty acids increased significantly with the dietary supplementation (p<0.05). Conclusions Daily intake of a combination of plant sterols, fish oil and B vitamins may modulate the lipid profile of hypercholesterolemic children and adolescents. Trial registration Current Controlled Trials ISRCTN89549017
Brassinosteroid\\/Sterol Synthesis and Plant Growth as Affected by lka and lkb Mutations of Pea1
The dwarf pea (Pisum sativum) mutants lka and lkb are brassi- nosteroid (BR) insensitive and deficient, respectively. The dwarf phenotype of the lkb mutant was rescued to wild type by exogenous application of brassinolide and its biosynthetic precursors. Gas chromatography-mass spectrometry analysis of the endogenous sterols in this mutant revealed that it accumulates 24- methylenecholesterol and isofucosterol but is deficient
Takahito Nomura; Yukiko Kitasaka; Suguru Takatsuto; James B. Reid; Motohiro Fukami; Takao Yokota
Intake occasion affects the serum cholesterol lowering of a plant sterol-enriched single-dose yoghurt drink in mildly hypercholesterolaemic subjects
Objective:To determine the impact of intake occasion (with or without a meal), and product fat level on the cholesterol-lowering efficacy of a plant sterol (PS)-enriched (3 g\\/day) single-dose yoghurt drink.Design:Double-blind, randomized, placebo-controlled, parallel study with a 4 weeks run-in and 4 weeks intervention period.Setting:Subjects recruited from the general community.Subjects:A total of 184 moderate hypercholesterolaemic subjects (81 men and 103 women)
A M E Doornbos; E M Meynen; G S M J E Duchateau; H C M van der Knaap; E A Trautwein
Metabolism of conjugated sterols in eggplant. Part 1. UDP-glucose : sterol glucosyltransferase.
A membrane-bound UDP-glucose : sterol glucosyltransferase from Solanum melongena (eggplant) leaves was partially purified and its specificity as well as molecular and kinetic properties were defined. Among a wide spectrum of 3-OH steroids (i.e. typical plant sterols, androstane, pregnane and cholestane derivatives, steroidal alkaloids and sapogenins) and triterpenic alcohols, the highest activity was found with 22-oxycholesterol. UDP-glucose appeared to be the best sugar donor. The enzyme preparation was also able to utilize UDP-galactose, TDP-glucose and CDP-glucose as a sugar source for sterol glucosylation, however, at distinctly lower rates. The investigated glucosyltrasferase was stimulated by 2-mercaptoethanol, Triton X-100 and negatively charged phospholipids, and inhibited in the presence of UDP, mono-, di- and triacylglycerols, divalent cations such as Zn(2+), Co(2+), high ionic strength, cholesteryl glucoside, galactoside and xyloside and some amino acid-modifying reagents (SITS, DIDS, PLP, DEPC, pCMBS, NEM, WRK and HNB). Our results suggest that unmodified residues of lysine, tryptophan, cysteine, histidine and dicarboxylic amino acids are essential for full enzymatic activity and indicate that a glutamic (or aspartic) acid residue is necessary for the binding of sugar donor, i.e. UDP-glucose in the active site of the GT-ase while histidine and cysteine residues are both important for the binding of the nucleotide-sugar as well as of the steroidal aglycone. PMID:18196184
Potocka, Anna; Zimowski, Jan
Deciphering the Molecular Functions of Sterols in Cellulose Biosynthesis
Sterols play vital roles in plant growth and development, as components of membranes and as precursors to steroid hormones. Analysis of Arabidopsis mutants indicates that sterol composition is crucial for cellulose biosynthesis. Sterols are widespread in the plasma membrane (PM), suggesting a possible link between sterols and the multimeric cellulose synthase complex. In one possible scenario, molecular interactions in sterol-rich PM microdomains or another form of sterol-dependent membrane scaffolding may be critical for maintaining the correct subcellular localization, structural integrity and/or activity of the cellulose synthase machinery. Another possible link may be through steryl glucosides, which could act as primers for the attachment of glucose monomers during the synthesis of ??(1???4) glucan chains that form the cellulose microfibrils. This mini-review examines genetic and biochemical data supporting the link between sterols and cellulose biosynthesis in cell wall formation and explores potential approaches to elucidate the mechanism of this association.
Schrick, Kathrin; DeBolt, Seth; Bulone, Vincent
Selective sterol accumulation in ABCG5/ABCG8-deficient mice.
The ATP binding cassette (ABC) transporters ABCG5 and ABCG8 limit intestinal absorption and promote biliary secretion of neutral sterols. Mutations in either gene cause sitosterolemia, a rare recessive disease in which plasma and tissue levels of several neutral sterols are increased to varying degrees. To determine why patients with sitosterolemia preferentially accumulate noncholesterol sterols, levels of cholesterol and the major plant sterols were compared in plasma, liver, bile, and brain of wild-type and ABCG5/ABCG8-deficient (G5G8(-/-)) mice. The total sterol content of liver and plasma was similar in G5G8(-/-) mice and wild-type animals despite an approximately 30-fold increase in noncholesterol sterol levels in the knockout animals. The relative enrichment of each sterol in the plasma and liver of G5G8(-/-) mice (stigmasterol > sitosterol = cholestanol > bassicasterol > campesterol > cholesterol) reflected its relative enrichment in the bile of wild-type mice. These results indicate that 24-alkylated, Delta22, and 5alpha-reduced sterols are preferentially secreted into bile and that preferential biliary secretion of noncholesterol sterols by ABCG5 and ABCG8 prevents the accumulation of these sterols in normal animals. The mRNA levels for 13 enzymes in the cholesterol biosynthetic pathway were reduced in the livers of the G5G8(-/-) mice, despite a 50% reduction in hepatic cholesterol level. Thus, the accumulation of sterols other than cholesterol is sensed by the cholesterol regulatory machinery. PMID:14657202
Yu, Liqing; von Bergmann, Klaus; Lutjohann, Dieter; Hobbs, Helen H; Cohen, Jonathan C
A ncovel angiogenic factor derived from Aloe vera gel: ?-sitosterol, a plant sterol
Aloe vera gel has a beneficial effect on wound healing. Because angiogenesis is an essential process in wound healing, we hypothesized\\u000a that Aloe vera gel might contain potent angiogenic compounds. Here we demonstrate that Aloe vera gel and its extracts are angiogenic on the chorioallantoic membrane (CAM) of chick embryo. Out of the three compounds purified\\u000a from the final fraction
Eun-Joung Moon; You Mie Lee; Ok-Hee Lee; Myoung-Jin Lee; Seung-Ki Lee; Myung-Hee Chung; Young-In Park; Chung-Ki Sung; Jae-Soo Choi; Kyu-Won Kim
A comparison of the behavior of cholesterol and selected derivatives in mixed sterol–phospholipid Langmuir monolayers: a fluorescence microscopy study
Eukaryotic cells require sterols to achieve normal structure and function of their plasma membranes, and deviations from normal sterol composition can perturb these features and compromise cellular and organism viability. The Smith–Lemli–Opitz syndrome (SLOS) is a hereditary metabolic disease involving cholesterol (CHOL) deficiency and abnormal accumulation of the CHOL precursor, 7-dehydrocholesterol (7DHC). In this study, the interactions of CHOL and
Erin E. Berring; Kimberly Borrenpohl; Steven J. Fliesler; Alexa Barnoski Serfis
Plant sterol-enriched margarines and reduction of plasma total- and LDL-cholesterol concentrations in normocholesterolaemic and mildly hypercholesterolaemic subjects
Objectives: To compare effects on plasma total-, LDL-, and HDL-cholesterol concentrations of margarines enriched with different vegetable oil sterols or sitostanol-ester.Design: A randomized double-blind placebo-controlled balanced incomplete Latin square design with five treatments and four periods of 3.5 weeks. Margarines enriched with sterols from soybean, sheanut or ricebran oil or with sitostanol-ester were compared to a non-enriched control margarine. Sterol
JA Weststrate; GW Meijer
Mediation of Elicitin Activity on Tobacco Is Assumed by Elicitin-Sterol Complexes
Elicitins secreted by phytopathogenic Phytophthora spp. are proteinaceous elicitors of plant de- fense mechanisms and were demonstrated to load, carry, and transfer sterols between mem- branes. The link between elicitor and sterol-loading properties was assessed with the use of site-directed mutagenesis of the 47 and 87 cryptogein tyrosine residues, postulated to be involved in sterol binding. Mutated cryptogeins were tested
Hanan Osman; Sebastien Vauthrin; Vladimir Mikes; Marie-Louise Milat; Franck Panabieres; Antoine Marais; Simone Brunie
Regulation of cholesterol biosynthesis in sitosterolemia: effects of lovastat in, cholestyramine, and dietary sterol restriction
We investigated the effects of lovastatin, cholestyra- mine, and dietary sterol restriction on cholesterol synthesis and low density lipoprotein receptor function in freshly isolated mononuclear leukocytes from two unrelated sitosterolemic fami- lies. Total plasma sterol concentrations were elevated in the two homozygous sitosterolemic subjects (343 and 301 vs. 185 mg\\/dl in controls) and contained increased amounts of plant sterols and
Lien B. Nguyen; Margaret Cobb; Sarah Shefer; Gerald Salen; Gene C. Ness
Animal Cell Mutants Defective in Sterol Metabolism: A Specific Selection Procedure and Partial Characterization of Defects
By using a chemically defined medium, a general and highly specific procedure was devised to select for mutant cells with less abundant or structurally altered sterol in their surface membranes. Within a certain concentration range, the polyene antibiotic filipin was shown to kill only cells with normal (as opposed to decreased) membrane sterol levels. Sterol-requiring derivatives of LM cells were
Y. Saito; S. M. Chou; D. F. Silbert
(24 S )-14?,24-dimethyl-9?,19-cyclo-5?-cholest-25-en-3?-ol: A new sterol and other sterols in Musa sapientum
The structure of a new sterol isolated fromMusa sapientum has been shown by chemical and spectroscopic methods to be (24S)-14?,24-dimethyl-9?,19-cyclo-5?-cholest-25-en-3?-ol. In addition, several known (24S)-24-methyl-?25-sterols, their 24-methylene isomers and other sterols (4,4-dimethyl-, 4?-methyl- and 4-demethyl-sterols) together with 3-oxo-4?-methylsteroids\\u000a were isolated from the plant and identified. The biogenetic implication of these sterols and 3-oxosteroids is discussed.
Toshihiro Akihisa; Naoto Shimizub; Toshitake Tamuraa; Taro Matsumotoa
Lipid-altering effects of a dietary supplement tablet containing free plant sterols and stanols in men and women with primary hypercholesterolaemia: a randomized, placebo-controlled crossover trial
This randomized, placebo-controlled, crossover trial assessed the lipid-altering efficacy of a dietary supplement (tablet form) providing 1.8g/day free (non-esterified) plant sterols and stanols versus placebo for 6 weeks as part of a therapeutic lifestyle changes (TLC) diet in 32 men and women with primary hypercholesterolaemia. Mean ± SE baseline (end of a 5-week TLC diet lead-in) lipid concentrations (mmol/1) were total cholesterol (TC), 5.88 ± 0.08; non-high-density lipoprotein cholesterol (non-HDL-C), 4.71 ± 0.09; low-density lipoprotein cholesterol (LDL-C), 4.02 ± 0.08; HDL-C, 1.17 ± 0.06 and triglycerides (TGs), 1.51 ± 0.12. Differences from control in responses (plant sterol/stanol — control) were significant (p < 0.05) for LDL-C (? 4.9%), non-HDL-C (? 3.6%) and TC (? 2.8%). HDL-C and TG responses were not significantly different between treatment conditions. These results indicate that 1.8g/day free plant sterols/stanols administered in a tablet produced favourable lipoprotein lipid changes in men and women with hypercholesterolaemia.
Maki, Kevin C; Lawless, Andrea L; Reeves, Matthew S; Dicklin, Mary R; Jenks, Belinda H; Shneyvas, ED; Brooks, James R
Lipid-altering effects of a dietary supplement tablet containing free plant sterols and stanols in men and women with primary hypercholesterolaemia: a randomized, placebo-controlled crossover trial.
This randomized, placebo-controlled, crossover trial assessed the lipid-altering efficacy of a dietary supplement (tablet form) providing 1.8 g/day free (non-esterified) plant sterols and stanols versus placebo for 6 weeks as part of a therapeutic lifestyle changes (TLC) diet in 32 men and women with primary hypercholesterolaemia. Mean ± SE baseline (end of a 5-week TLC diet lead-in) lipid concentrations (mmol/l) were total cholesterol (TC), 5.88 ± 0.08; non-high-density lipoprotein cholesterol (non-HDL-C), 4.71 ± 0.09; low-density lipoprotein cholesterol (LDL-C), 4.02 ± 0.08; HDL-C, 1.17 ± 0.06 and triglycerides (TGs), 1.51 ± 0.12. Differences from control in responses (plant sterol/stanol - control) were significant (p < 0.05) for LDL-C ( - 4.9%), non-HDL-C ( - 3.6%) and TC ( - 2.8%). HDL-C and TG responses were not significantly different between treatment conditions. These results indicate that 1.8 g/day free plant sterols/stanols administered in a tablet produced favourable lipoprotein lipid changes in men and women with hypercholesterolaemia. PMID:22087585
Maki, Kevin C; Lawless, Andrea L; Reeves, Matthew S; Dicklin, Mary R; Jenks, Belinda H; Shneyvas, Ed; Brooks, James R
Effects of dietary plant meal and soya-saponin supplementation on intestinal and hepatic lipid droplet accumulation and lipoprotein and sterol metabolism in Atlantic salmon (Salmo salar L.).
Altered lipid metabolism has been shown in fish fed plant protein sources. The present study aimed to gain further insights into how intestinal and hepatic lipid absorption and metabolism are modulated by plant meal (PM) and soya-saponin (SA) inclusion in salmon feed. Post-smolt Atlantic salmon were fed for 10 weeks one of four diets based on fishmeal or PM, with or without 10 g/kg SA. PM inclusion resulted in decreased growth performance, excessive lipid droplet accumulation in the pyloric caeca and liver, and reduced plasma cholesterol levels. Intestinal and hepatic gene expression profiling revealed an up-regulation of the expression of genes involved in lipid absorption and lipoprotein (LP) synthesis (apo, fatty acid transporters, microsomal TAG transfer protein, acyl-CoA cholesterol acyltransferase, choline kinase and choline-phosphate cytidylyltransferase A), cholesterol synthesis (3-hydroxy-3-methylglutaryl-CoA reductase) and associated transcription factors (sterol regulatory element-binding protein 2 and PPAR?). SA inclusion resulted in reduced body pools of cholesterol and bile salts. The hepatic gene expression of the rate-limiting enzyme in bile acid biosynthesis (cytochrome P450 7A1 (cyp7a1)) as well as the transcription factor liver X receptor and the bile acid transporter abcb11 (ATP-binding cassette B11) was down-regulated by SA inclusion. A significant interaction was observed between PM inclusion and SA inclusion for plasma cholesterol levels. In conclusion, gene expression profiling suggested that the capacity for LP assembly and cholesterol synthesis was up-regulated by PM exposure, probably as a compensatory mechanism for excessive lipid droplet accumulation and reduced plasma cholesterol levels. SA inclusion had hypocholesterolaemic effects on Atlantic salmon, accompanied by decreased bile salt metabolism. PMID:24507758
Gu, Min; Kortner, Trond M; Penn, Michael; Hansen, Anne Kristine; Krogdahl, Ĺshild
SHRSP/Izm and WKY/NCrlCrlj rats having a missense mutation in Abcg5 deposited plant sterols in the body, but did not change their biliary secretion and lymphatic absorption-comparison with Jcl:Wistar and WKY/Izm rats.
We had previously found plant sterols deposited in the bodies of stroke-prone spontaneously hypertensive rats (SHRSP)/Sea and Wistar Kyoto (WKY)/NCrlCrlj rats that had a missense mutation in the Abcg5 cDNA sequence that coded for ATP-binding cassette transporter (ABC) G5. We used SHRSP/Izm, WKY/NCrlCrlj, and WKY/Izm rats in the present study to determine the mechanisms for plant sterol deposition in the body. Jcl:Wistar rats were used as a control strain. A diet containing 0.5% plant sterols fed to the rats resulted in plant sterol deposition in the body of SHRSP/Izm, but not in WKY/Izm or Jcl:Wistar rats. Only a single non-synonymous nucleotide change, G1747T, resulting in a conservative cysteine substitution for glycine at amino acid 583 (Gly583Cys) in Abcg5 cDNA was identified in the SHRSP/Izm and WKY/NCrlCrlj rats. However, this mutation was not found in the WKY/Izm or Jcl:Wistar rats. No significant difference in the biliary secretion or lymphatic absorption of plant sterols was apparent between the rat strains with or without the missense mutation in Abcg5 cDNA. Our observations suggest that plant sterol deposition in rat strains with the missense mutation in Abcg5 cDNA can occur, despite there being no significant change in the biliary secretion or lymphatic absorption of plant sterols. PMID:22484926
Kato, Masaki; Ito, Yusuke; Tanaka, Yasutake; Sato, Masao; Imaizumi, Katsumi; Inoue, Nao; Ikeda, Ikuo
Lactoferrin-derived resistance against plant pathogens in transgenic plants.
Lactoferrin (LF) is a ubiquitous cationic iron-binding milk glycoprotein that contributes to nutrition and exerts a broad-spectrum primary defense against bacteria, fungi, protozoa, and viruses in mammals. These qualities make lactoferrin protein and its antimicrobial motifs highly desirable candidates to be incorporated in plants to impart broad-based resistance against plant pathogens or to economically produce them in bulk quantities for pharmaceutical and nutritional purposes. This study introduced bovine LF (BLF) gene into tobacco ( Nicotiana tabacum var. Xanthi), Arabidopsis ( A. thaliana ) and wheat ( Triticum aestivum ) via Agrobacterium -mediated plant transformation. Transgenic plants or detached leaves exhibited high levels of resistance against the damping-off causing fungal pathogen Rhizoctonia solani and the head blight causing fungal pathogen Fusarium graminearum . LF also imparted resistance to tomato plants against a bacterial pathogen, Ralstonia solanacearum . Similarly, other researchers demonstrated expression of LF and LF-mediated high-quality resistance to several other aggressive fungal and bacterial plant pathogens in transgenic plants and against viral pathogens by foliar applications of LF or its derivatives. Taken together, these studies demonstrated the effectiveness of LF for improving crop quality and its biopharming potentials for pharmaceautical and nutritional applications. PMID:23889215
Lakshman, Dilip K; Natarajan, Savithiry; Mandal, Sudhamoy; Mitra, Amitava
A marked and sustained reduction in LDL sterols by diet and cholestyramine in beta-sitosterolemia.
This study examines the therapeutic outcome of a low plant sterol diet and adjunctive drug therapy (cholestyramine) in the long term treatment of beta-sitosterolemia. A diet restricted in plant sterols, cholesterol and fat was implemented in a 48-year-old male beta-sitosterolemic patient. The plant sterols beta-sitosterol, campesterol and stigmasterol, and cholesterol content of the diet were quantitated by a gas chromatography method (GLC) during metabolic ward studies. Food table analysis of dietary sterols, while quantitatively similar to GLC, significantly underestimated the level of plant sterols and therefore overestimated dietary cholesterol intake. The duration of the study was 18 months. The effect of the diet over a period of 6 months on the sterol levels of plasma and individual lipoprotein fractions (VLDL, LDL, HDL) was evaluated. Apolipoproteins A-1 and B-100 levels were measured. The same parameters were assessed over the next 12 months with the adjunctive use of cholestyramine and dietary restrictions. The diet was effective in lowering total, VLDL, and LDL plant sterols by 37%, 59%, and 32% respectively. The low plant sterol diet did not change total plasma, VLDL or LDL cholesterol. With the addition of cholestyramine, total plasma and LDL cholesterol declined by 64 and 76%, respectively, while HDL-cholesterol remained unchanged. LDL plant sterols declined by 77%, while VLDL plant sterol showed no further change. The decline showed no discrimination among the individual plant sterols. One week after cholestyramine therapy, apolipoprotein B fell from 1.03 to 0.11 g/L, while apolipoprotein A rose from 1.29 to 1.79 g/L. These levels subsequently stabilized at 70% below (0.29 g/L) and 42% above (1.81 g/L) that of diet therapy alone. Xanthomas, angina pectoris, and intermittent claudication resolved during the diet and cholestyramine therapy period. Dietary restriction of plant sterols combined with cholestyramine therapy is an effective means of treating beta-sitosterolemia. PMID:8529322
Parsons, H G; Jamal, R; Baylis, B; Dias, V C; Roncari, D
Association of Natural Intake of Dietary Plant Sterols with Carotid Intima-Media Thickness and Blood Lipids in Chinese Adults: A Cross-Section Study
Background Many studies showed a moderate cholesterol-lowering effect of plant sterols (PS), but increased circulating PS might be atherogenic. We evaluated the associations between natural dietary intake of PS and carotid intima–media thickness (IMT) and serum lipids. Methodology/Principal Findings This community-based cross-sectional study included 1160 men and 2780 women aged 31–75 years. Dietary intakes were assessed using a food-frequency questionnaire. The IMTs at the common, bifurcation and internal carotid artery segments, and fasting serum total (TC), LDL (LDLc) and HDL (HDLc) cholesterol, and triglycerides (TG) were determined. After adjusting for potential covariates, multivariate analysis showed a dose-dependent inverse association of total PS intake with serum TC, LDLc, non-HDLc in women (P<0.001) and in men (P<0.05). As compared to the lowest quartile of PS intake (<206 mg/d), the multivariate-adjusted means of TC, LDLc and non-HDLc in the highest quartile of PS intake (447 mg/d) decreased by 5.0%, 6.2% and 6.5% in women (P<0.005), and by 6.4%, 7.1% and 6.7% (P>0.05) in men. Although the IMTs tended to be lower with greater intake of dietary PS, only small differences in the left internal IMT between the highest and lowest groups were observed among men (?7.6%) and women (?5.1%) (P<0.05). The multivariate analysis showed no significant mean differences among the PS groups in HDLc, TG and IMTs at other studied sites among men and women (all P>0.05). Conclusions Greater PS consumption from natural diets is associated with lower serum total, LDL, non-HDL cholesterol and with thinner left internal IMT in women and men.
Wang, Ping; Chen, Yu-ming; He, Li-ping; Chen, Chao-gang; Zhang, Bo; Xue, Wen-qiong; Su, Yi-xiang
Final report of the amended safety assessment of PEG-5, -10, -16, -25, -30, and -40 soy sterol.
PEGs Soy Sterol are polyethylene glycol (PEG) derivatives of soybean oil sterols used in a variety of cosmetic formulations as surfactants and emulsifying agents, skin-conditioning agents, and cleansing and solubilizing agents. When the safety of these ingredients were first reviewed, the available data were insufficient to support safety. New data have since been received and the safety of these ingredients in cosmetics has been substantiated. Current concentration of use ranges from a low of 0.05% in makeup preparations to 2% in moisturizers and several other products. PEGs Soy Sterol are produced by the reaction of the soy sterol hydroxyl with ethylene oxide. In general, ethoxylated fatty acids can contain 1,4-dioxane as a byproduct of ethoxylation. The soy sterols include campesterol, stigmasterol, and beta-sitosterol. The distribution of sterols found in oils derived from common plants is similar, with beta-sitosterol comprising a major component. Impurities include sterol hydrocarbons and cholesterol (4% to 6%) and triterpine alcohols, keto-steroids, and other steroid-like substances (4% to 6%). No pesticide residues were detected. PEGS: Because PEGs are an underlying structure in PEGs Soy Sterols, the previous assessment of PEGs was considered. It is generally recognized that the PEG monomer, ethylene glycol, and certain of its monoalkyl ethers are reproductive and developmental toxins. Given the methods of manufacture of PEGs Soy Sterol, there is no likelihood of ethylene glycol or its alkyl ethers being present. Also, the soybean oil sterol ethers in this ingredient are chemically different from the ethylene glycol alkyl ethers of concern. PEGs are not carcinogenic, although sensitization and nephrotoxicity were observed in burn patients treated with a PEG-based cream. No evidence of systemic toxicity or sensitization was found in studies with intact skin. Plant Phytosterols: Intestinal absorption of ingested plant phytosterols is on the order of 5%, with 95% of the material entering the colon. Absorbed plant phytosterols are transported to the blood. Although there are some data suggesting that sulfates of beta-sitosterol can act as abortifacients in rats and rabbits, other studies of well-characterized plant phytosterols and phytosterol esters demonstrated no effect in an estrogen-binding study, a recombinant yeast assay for estrogen or estrogen-like activity, or a juvenile rat uterotrophic assay for estrogen or estrogen-like activity. In a two-generation reproduction study using rats, plant phytosterol esters in the diet had no effect on any parameter of reproduction or fertility. Subcutaneous injections of beta-sitosterol did reduce sperm concentrations and fertility in rats. Sitosterol inhibited tumor promoting activity of 12-O-tetradecanoylphorbol-13-acetate (TPA) in mice after initiation with 7,12-dimethylbenz[a]anthracene (DMBA), and reduced the tumors produced by N-methylnitrosourea in rats. Phytosterols were not genotoxic in several bacterial, mammalian, and in vitro assay systems. Phytosterols decreased epithelial cell proliferation in the colon of mice and rats, and were cytotoxic for human epidermoid carcinoma of the nasopharynx. PEGs Soy Sterols: The acute oral LD50 in rats of PEG-5-25 Soy Sterol was >10 g/kg. The acute dermal LD50 of a liquid eyeliner containing 2%PEG-5 Soy Sterol was >2 g/kg in rabbits. PEG-5-25 Soy Sterol was not a primary irritant in rabbits when applied undiluted. Undiluted PEG-5 Soy Sterol did not cause sensitization in guinea pigs. PEGs Soy Sterol did not produce ocular toxicity in rabbits. PEG-5 Soy Sterol was negative in the Ames mutagenicity test, with or without metabolic activation. PEG-5 Soy Sterol, at concentrations up to 2%in formulation, did not cause dermal or ocular irritation, dermal sensitization, or photosensitization in clinical studies. Because of the possible presence of 1,4-dioxane reaction product and unreacted ethylene oxide residues, it was considered necessary to use appropriate procedures to remove these from PEGs Soy Sterol before blending them
Phylogenetic Distribution of Fungal Sterols
Background Ergosterol has been considered the "fungal sterol" for almost 125 years; however, additional sterol data superimposed on a recent molecular phylogeny of kingdom Fungi reveals a different and more complex situation. Methodology/Principal Findings The interpretation of sterol distribution data in a modern phylogenetic context indicates that there is a clear trend from cholesterol and other ?5 sterols in the earliest diverging fungal species to ergosterol in later diverging fungi. There are, however, deviations from this pattern in certain clades. Sterols of the diverse zoosporic and zygosporic forms exhibit structural diversity with cholesterol and 24-ethyl -?5 sterols in zoosporic taxa, and 24-methyl sterols in zygosporic fungi. For example, each of the three monophyletic lineages of zygosporic fungi has distinctive major sterols, ergosterol in Mucorales, 22-dihydroergosterol in Dimargaritales, Harpellales, and Kickxellales (DHK clade), and 24-methyl cholesterol in Entomophthorales. Other departures from ergosterol as the dominant sterol include: 24-ethyl cholesterol in Glomeromycota, 24-ethyl cholest-7-enol and 24-ethyl-cholesta-7,24(28)-dienol in rust fungi, brassicasterol in Taphrinales and hypogeous pezizalean species, and cholesterol in Pneumocystis. Conclusions/Significance Five dominant end products of sterol biosynthesis (cholesterol, ergosterol, 24-methyl cholesterol, 24-ethyl cholesterol, brassicasterol), and intermediates in the formation of 24-ethyl cholesterol, are major sterols in 175 species of Fungi. Although most fungi in the most speciose clades have ergosterol as a major sterol, sterols are more varied than currently understood, and their distribution supports certain clades of Fungi in current fungal phylogenies. In addition to the intellectual importance of understanding evolution of sterol synthesis in fungi, there is practical importance because certain antifungal drugs (e.g., azoles) target reactions in the synthesis of ergosterol. These findings also invalidate use of ergosterol as an indicator of biomass of certain fungal taxa (e.g., Glomeromycota). Data from this study are available from the Assembling the Fungal Tree of Life (AFTOL) Structural and Biochemical Database: http://aftol.umn.edu.
Weete, John D.; Abril, Maritza; Blackwell, Meredith
The effects of sterol structure upon sterol esterification.
Cholesterol is esterified in mammals by two enzymes: LCAT (lecithin cholesterol acyltransferase) in plasma and ACAT(1) and ACAT(2) (acyl-CoA cholesterol acyltransferases) in the tissues. We hypothesized that the sterol structure may have significant effects on the outcome of esterification by these enzymes. To test this hypothesis, we analyzed sterol esters in plasma and tissues in patients having non-cholesterol sterols (sitosterolemia and Smith-Lemli-Opitz syndrome). The esterification of a given sterol was defined as the sterol ester percentage of total sterols. The esterification of cholesterol in plasma by LCAT was 67% and in tissues by ACAT was 64%. Esterification of nine sterols (cholesterol, cholestanol, campesterol, stigmasterol, sitosterol, campestanol, sitostanol, 7-dehydrocholesterol and 8-dehydrocholesterol) was examined. The relative esterification (cholesterol being 1.0) of these sterols by the plasma LCAT was 1.00, 0.95, 0.89, 0.40, 0.85, 0.82 and 0.80, 0.69 and 0.82, respectively. The esterification by the tissue ACAT was 1.00, 1.29, 0.75, 0.49, 0.45, 1.21 and 0.74, respectively. The predominant fatty acid of the sterol esters was linoleic acid for LCAT and oleic acid for ACAT. We compared the esterification of two sterols differing by only one functional group (a chemical group attached to sterol nucleus) and were able to quantify the effects of individual functional groups on sterol esterification. The saturation of the A ring of cholesterol increased ester formation by ACAT by 29% and decreased the esterification by LCAT by 5.9%. Esterification by ACAT and LCAT was reduced, respectively, by 25 and 11% by the presence of an additional methyl group on the side chain of cholesterol at the C-24 position. This data supports our hypothesis that the structure of the sterol substrate has a significant effect on its esterification by ACAT or LCAT. PMID:19679306
Lin, Don S; Steiner, Robert D; Merkens, Louise S; Pappu, Anuradha S; Connor, William E
Biological Activity of Some Oxygenated Sterols
A group of oxygenated sterols has been identified as potent and specific inhibitors of sterol biosynthesis. The ability of these compounds to inhibit sterol synthesis in cultured cells and the ineffectiveness of cholesterol under the same conditions suggest that feedback regulation of sterol biosynthesis may be brought about by an oxygenated sterol rather than by cholesterol. The nature of the
Andrew A. Kandutsch; Harry W. Chen; Hans-Jorg Heiniger
Arabidopsis ERG28 tethers the sterol C4-demethylation complex to prevent accumulation of a biosynthetic intermediate that interferes with polar auxin transport.
Sterols are vital for cellular functions and eukaryotic development because of their essential role as membrane constituents. Sterol biosynthetic intermediates (SBIs) represent a potential reservoir of signaling molecules in mammals and fungi, but little is known about their functions in plants. SBIs are derived from the sterol C4-demethylation enzyme complex that is tethered to the membrane by Ergosterol biosynthetic protein28 (ERG28). Here, using nonlethal loss-of-function strategies focused on Arabidopsis thaliana ERG28, we found that the previously undetected SBI 4-carboxy-4-methyl-24-methylenecycloartanol (CMMC) inhibits polar auxin transport (PAT), a key mechanism by which the phytohormone auxin regulates several aspects of plant growth, including development and responses to environmental factors. The induced accumulation of CMMC in Arabidopsis erg28 plants was associated with diagnostic hallmarks of altered PAT, including the differentiation of pin-like inflorescence, loss of apical dominance, leaf fusion, and reduced root growth. PAT inhibition by CMMC occurs in a brassinosteroid-independent manner. The data presented show that ERG28 is required for PAT in plants. Furthermore, it is accumulation of an atypical SBI that may act to negatively regulate PAT in plants. Hence, the sterol pathway offers further prospects for mining new target molecules that could regulate plant development. PMID:24326590
Mialoundama, Alexis Samba; Jadid, Nurul; Brunel, Julien; Di Pascoli, Thomas; Heintz, Dimitri; Erhardt, Mathieu; Mutterer, Jérôme; Bergdoll, Marc; Ayoub, Daniel; Van Dorsselaer, Alain; Rahier, Alain; Nkeng, Paul; Geoffroy, Philippe; Miesch, Michel; Camara, Bilal; Bouvier, Florence
Identification and significance of sterols in MSW landfill leachate.
The sterol content of leachate from two different landfills (labeled as landfill J and landfill R, respectively) at Wuhan, central China was examined by GC/MS. About 20 types of sterols were identified according to their mass spectra of TMS (trimethylsilyl derivates) ethers and their eluting orders. Three types of indices of sterols, namely the ratio of 5beta/(5beta+5alpha) stanol, the ratio of coprostanol/epicoprostanol and the ratio of coprostanol/cholesterol, were used to assess and cross-validate sterol sources. The results showed that landfill R suffered faecal pollution while there are complex sterol sources in landfill J. The ratios of cholesterol/(chloesterol+cholestanol) were 0.24 in landfill R and 0.32 in landfill J, indicating cholesterol reduction in both landfills. C29 sterols consisted of 58% of total sterols in landfill J leachate. The sources for the landfill leachate included not only allochthonous domestic wastes, but biodegradation products of autochthonous wastes in the landfills. PMID:18818129
Zhang, Caixiang; Wang, Yanxin; Qi, Shihua
Sterol C-24 Methyltransferase Type 1 Controls the Flux of Carbon into Sterol Biosynthesis in Tobacco Seed
The first committed step in the conversion of cycloartenol into ?5 C24-alkyl sterols in plants is catalyzed by an S-adenosyl-methionine-dependent sterol-C24-methyltransferase type 1 (SMT1). We report the consequences of overexpressing SMT1 in tobacco (Nicotiana tabacum), under control of either the constitutive carnation etched ring virus promoter or the seed-specific Brassica napus acyl-carrier protein promoter, on sterol biosynthesis in seed tissue. Overexpression of SMT1 with either promoter increased the amount of total sterols in seed tissue by up to 44%. The sterol composition was also perturbed with levels of sitosterol increased by up to 50% and levels of isofucosterol and campesterol increased by up to 80%, whereas levels of cycloartenol and cholesterol were decreased by up to 53% and 34%, respectively. Concomitant with the enhanced SMT1 activity was an increase in endogenous 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, from which one can speculate that reduced levels of cycloartenol feed back to up-regulate 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and thereby control the carbon flux into sterol biosynthesis. This potential regulatory role of SMT1 in seed sterol biosynthesis is discussed.
Holmberg, Niklas; Harker, Mark; Gibbard, Carl L.; Wallace, Andrew D.; Clayton, John C.; Rawlins, Sally; Hellyer, Amanda; Safford, Richard
Plant Derived Therapeutic Agents: The Indian Experience.
National Technical Information Service (NTIS)
Contents: Research and development for the utilisation of medicinal plants for therapeutic use; Traditional system remedies; Broad spectrum biological screening of plants; Cultivation of medicinal plants; Phytochemical industry; Regional medicinal plants ...
N. Anand
A two-carbon switch to sterol-induced autophagic death.
Although both cholesterol and plant sterols are abundant in our diets, our intestinal epithelial cells selectively and efficiently rid the body of plant sterols. However, a rare mutation in plant sterol excretion in humans results in the accumulation of plant sterols, particularly sitosterol, in the plasma and tissues. Sitosterol differs from cholesterol only in an extra ethyl group on the sterol side chain. Significantly, sitosterolemia is associated with accelerated atherothrombotic vascular disease, notably myocardial infarction. An important process that promotes atherothrombosis is advanced lesional macrophage death, leading to plaque necrosis. One of the causes of atherosclerotic macrophage death is sterol-induced cytotoxicity. We therefore compared the effects of excess intracellular sitosterol vs. cholesterol on macrophage death. Whereas excess cholesterol kills macrophages by caspase-dependent apoptosis, sitosterol kills macrophages by a caspase-independent pathway involving necroptosis and autophagy. The finding that an ethyl group on the sterol side chain fundamentally alters the way cells respond to excess sterols adds new insight into the mechanisms of sterol-induced cell death and may provide at least one explanation for the excess atherosclerotic heart disease in patients with sitosterolemia. PMID:17172803
Tabas, Ira
Free and glycosylated sterol bioaccumulation in developing Cycas micronesica seeds
The bioaccumulation of free and glycosylated forms of stigmasterol and ?-sitosterol were determined from Cycas micronesica K.D. Hill seeds throughout seed ontogeny. Per-seed pool of the four compounds increased linearly from 2 to 24 months, indicating no developmental period elicited a major shift in the rate of bioaccumulation. The slopes were not homogeneous, signifying a change in relative sterol profile concomitant with seed maturation. This shift was in favour of the glucosides, as their rate of accumulation exceeded that of the free sterols. Stigmasterol content exceeded that of ?-sitosterol, but ontogeny did not influence the ratio of these dominant sterols. The quantity and quality of sterol exposure during consumption of foods prepared from gametophytes by humans is strongly influenced by age of harvested seeds. Results are critical for a further understanding of the link between human neurodegenerative diseases and historical consumption of foods derived from the seed gametophyte tissue.
Marler, Thomas E.; Shaw, Christopher A.
Sterol effects and sites of sterol accumulation in Caenorhabditis elegans: developmental requirement for 4alpha-methyl sterols
Caenorhabditis elegans requires sterol, usually sup- plied as cholesterol, but this is enzymatically modified, and different sterols can substitute. Sterol deprivation de- creased brood size and adult growth in the first generation, and completely, reversibly, arrested growth as larvae in the second. After one generation of sterol deprivation, 10 ng\\/ml cholesterol allowed delayed laying of a few eggs, but full
Mark Merris; William G. Wadsworth; Uttam Khamrai; Robert Bittman; David J. Chitwood; John Lenard
Phase change ink comprising colorants derived from plants and insects
US Patent & Trademark Office Database
A phase change ink composition including a wax; an optional dispersant; an optional synergist; and a naturally-derived colorant wherein the naturally-derived colorant is a colorant derived from a plant, a colorant derived from an insect, or a mixture or combination thereof.
Agrobacterium tumefaciens responses to plant-derived signaling molecules
As a special phytopathogen, Agrobacterium tumefaciens infects a wide range of plant hosts and causes plant tumors also known as crown galls. The complexity of Agrobacterium–plant interaction has been studied for several decades. Agrobacterium pathogenicity is largely attributed to its evolved capabilities of precise recognition and response to plant-derived chemical signals. Agrobacterium perceives plant-derived signals to activate its virulence genes, which are responsible for transferring and integrating its Transferred DNA (T-DNA) from its Tumor-inducing (Ti) plasmid into the plant nucleus. The expression of T-DNA in plant hosts leads to the production of a large amount of indole-3-acetic acid (IAA), cytokinin (CK), and opines. IAA and CK stimulate plant growth, resulting in tumor formation. Agrobacterium utilizes opines as nutrient sources as well as signals in order to activate its quorum sensing (QS) to further promote virulence and opine metabolism. Intriguingly, Agrobacterium also recognizes plant-derived signals including ?-amino butyric acid and salicylic acid (SA) to activate quorum quenching that reduces the level of QS signals, thereby avoiding the elicitation of plant defense and preserving energy. In addition, Agrobacterium hijacks plant-derived signals including SA, IAA, and ethylene to down-regulate its virulence genes located on the Ti plasmid. Moreover, certain metabolites from corn (Zea mays) also inhibit the expression of Agrobacterium virulence genes. Here we outline the responses of Agrobacterium to major plant-derived signals that impact Agrobacterium–plant interactions.
Subramoni, Sujatha; Nathoo, Naeem; Klimov, Eugene; Yuan, Ze-Chun
Study of Behavior of Sterols at Interfaces
NASA Technical Reports Server (NTRS)
Behavior of sterols and sterol acetates on various types of interfaces indicates that the function of a sterol depends upon a surface orientation and surface energy of the interface. Column-chromatographic techniques determine the retention volume of various sterols under standard conditions.
Klein, P. D.; Knight, J. C.; Szczepanik, P. A.
Andrographolide: A New Plant-Derived Antineoplastic Entity on Horizon
Plant-derived natural products occupy an important position in the area of cancer chemo- therapy. Molecules such as vincristine, vinblastine, paclitaxel, camptothecin derivatives, epipo- dophyllotoxin, etc. are invaluable contributions of nature to modern medicine. However, the quest to find out novel therapeutic compounds for cancer treatment and management is a never-ending venture; and diverse plant species are persistently being studied for
Astha Varma; Harish Padh; Neeta Shrivastava
Requirement of sterols in the life cycle of the nematode Caenorhabditis elegans
The nematode Caenorhabditis elegans represents an excellent model for studying many aspects of sterol function on the level of a whole organism. Recent studies show that especially two processes in the life cycle of the worm, dauer larva formation and molting, depend on sterols. In both cases, cholesterol or its derivatives seem to act as hormones rather than being structural
Eugeni V. Entchev; Teymuras V. Kurzchalia
Sterol Lipid Metabolism in Down Syndrome Revisited: Down Syndrome Is Associated with a Selective Reduction in Serum Brassicasterol Levels
Over the past 15 years, insights into sterol metabolism have improved our understanding of the relationship between lipids and common conditions such as atherosclerosis and Alzheimer's Disease (AD). A better understanding of sterol lipid metabolism in individuals with Down Syndrome (DS) may help elucidate how this population's unique metabolic characteristics influence their risks for atherosclerosis and AD. To revisit the question of whether sterol lipid parameters may be altered in DS subjects, we performed a pilot study to assess traditional serum sterol lipids and lipoproteins, as well as markers of sterol biosynthesis, metabolites, and plant sterols in 20 subjects with DS compared to age-matched controls. Here we report that the levels of nearly all lipids and lipoproteins examined are similar to control subjects, suggesting that trisomy 21 does not lead to pronounced general alterations in sterol lipid metabolism. However, the levels of serum brassicasterol were markedly reduced in DS subjects.
Tansley, Gavin; Holmes, Daniel T.; Lutjohann, Dieter; Head, Elizabeth; Wellington, Cheryl L.
Plant-derived vaccines against diarrheal diseases.
Transgenic plants present a novel system for both production and oral delivery of vaccine antigens. Production of protein antigen in food plants is substantially cheaper than production in bacterial, fungal, insect cell, or mammalian cell culture. Edible plants themselves can also serve as the oral vaccine delivery system. Phase-1 studies of raw transgenic potatoes expressing the B subunit of Escherichia coli heat labile enterotoxin (LT-B), potatoes expressing Norwalk virus capsid protein, and defatted corn germ meal expressing LT-B have been conducted. New oral vaccines based on other transgenic plants will soon be evaluated in humans. PMID:15734057
Tacket, Carol O
Pathogen derived elicitors: searching for receptors in plants
SUMMARY Recognition of potential pathogens is central to plants' ability to defend themselves against harmful microbes. Plants are able to recognize pathogen-derived molecules; elicitors that trigger a number of induced defences in plants. Microbial elicitors constitute a bewildering array of compounds including different oligosaccharides, lipids, peptides and proteins. Identifying the receptors for this vast array of elicitors is a major
Marcos Montesano; Gunter Brader; E. Tapio Palva
Plant sterols, marine-derived omega-3 fatty acids and other functional ingredients: a new frontier for treating hyperlipidemia
As hyperlipidemia, including hypercholesterolemia (HC) and hypertriglyceridemia (HTN), continue to challenge North America's healthcare systems, patients continue to seek efficacious and safe natural therapies that complement pharmaceutical interventions. However, despite the ever-growing body of research supporting the use of functional foods and nutraceuticals (FFN) for the prevention and treatment of hyperlipidemia, reception amongst the medical community regarding the implementation of
Christopher PF Marinangeli; Peter JH Jones
A softgel dietary supplement containing esterified plant sterols and stanols improves the blood lipid profile of adults with primary hypercholesterolemia: a randomized, double-blind, placebo-controlled replication study.
A well-controlled clinical trial previously demonstrated the efficacy of a novel softgel dietary supplement providing 1.8 g/day esterified plant sterols and stanols, as part of the National Cholesterol Education Program Therapeutic Lifestyle Changes diet, to improve the fasting lipid profile of men and women with primary hypercholesterolemia (fasting low-density lipoprotein [LDL] cholesterol ? 130 and <220 mg/dL [? 3.37 and <5.70 mmol/L]). The purpose of this randomized, double blind, placebo-controlled crossover study (conducted July 2011 to January 2012) was to support these previous findings in a similar, but independent, sample with a different lead investigator and research site. Repeated measures analysis of covariance was used to compare outcomes for sterol/stanol and placebo treatment conditions using the baseline value as a covariate. Forty-nine subjects were screened and 30 (8 men and 22 women) were randomized to treatment (all completed the trial). Baseline (mean ± standard error of the mean) plasma lipid concentrations were: total cholesterol 236.6 ± 4.2 mg/dL (6.11 ± 0.11 mmol/L), high-density lipoprotein (HDL) cholesterol 56.8 ± 3.0 mg/dL (1.47 ± 0.08 mmol/L), LDL cholesterol 151.6 ± 3.3 mg/dL (3.92 ± 0.09 mmol/L), non-HDL cholesterol 179.7 ± 4.6 mg/dL (4.64 ± 0.12 mmol/L), and triglycerides 144.5 ± 14.3 mg/dL (1.63 ± 0.16 mmol/L). Mean placebo-adjusted reductions in plasma lipid levels were significant (P<0.01) for LDL cholesterol (-4.3%), non-HDL cholesterol (-4.1%), and total cholesterol (-3.5%), but not for triglycerides or HDL cholesterol. These results support the efficacy of 1.8 g/day esterified plant sterols/stanols in softgel capsules, administered as an adjunct to the National Cholesterol Education Program Therapeutic Lifestyle Changes diet, to augment reductions in atherogenic lipid levels in individuals with hypercholesterolemia. PMID:24287284
McKenney, James M; Jenks, Belinda H; Shneyvas, Ed; Brooks, James R; Shenoy, Sonia F; Cook, Chad M; Maki, Kevin C
Propiconazole inhibits the sterol 14?-demethylase in Glomus irregulare like in phytopathogenic fungi.
The increasing concentrations impact (0.02, 0.2 and 2 mg L(-1)) of a Sterol Biosynthesis Inhibitor (SBI) fungicide, propiconazole, was evaluated on development and sterol metabolism of two non-target organisms: mycorrhizal or non-mycorrhizal transformed chicory roots and the arbuscular mycorrhizal fungus (AMF) Glomus irregulare using monoxenic cultures. In this work, we provide the first evidence of a direct impact of propiconazole on the AMF by disturbing its sterol metabolism. A significant decrease in end-products sterols contents (24-methylcholesterol and in 24-ethylcholesterol) was observed concomitantly to a 24-methylenedihydrolanosterol accumulation indicating the inhibition of a key enzyme in sterol biosynthesis pathway, the sterol 14?-demethylase like in phytopathogenic fungi. A decrease in end-product sterol contents in propiconazole-treated roots was also observed suggesting a slowing down of the sterol metabolism in plant. Taken together, our findings suggest that the inhibition of the both AM symbiotic partners development by propiconazole results from their sterol metabolism alterations. PMID:22239944
Calonne, Maryline; Sahraoui, Anissa Lounčs-Hadj; Campagnac, Estelle; Debiane, Djouher; Laruelle, Frédéric; Grandmougin-Ferjani, Anne; Fontaine, Joël
The content and composition of sterols and sterol esters in low erucic acid rapeseed ( Brassica napus )
The low temperature crystallization technique for the enrichment of "minor" components, such as sterols and sterol esters,\\u000a from vegetable oils was applied to low erucic acid rapeseed oils. The recovery of free sterols and sterol esters was estimated\\u000a by use of14C-cholesterol and14C-cholesterol oleate. 80% of the free sterols and 45% of the sterol esters were recovered in the liquid fraction,
Anna Johansson; Lars-Ĺke Appelqvist
Application of comprehensive two-dimensional gas chromatography to the quantification of overlapping faecal sterols.
Standard solutions containing a mixture of seven sterols and 5alpha-cholestane as internal standard, and sample mixtures that comprised varying ratios of sterol and stanols from green lip mussel tissue and dried cow faeces were analysed by using comprehensive two-dimensional gas chromatography (GC x GC). Quantitative results were compared with single-column GC analysis. The latter samples included sterols of interest, but which cannot be readily obtained elsewhere. It may also mimic potential environmental samples where dairy production and aquaculture (oyster, mussel cultivation) share the same catchment; environmental sterol signatures may exhibit characteristics of both sample types comprising this mixture. Whereas single-column GC-flame ionisation detection was unable to reliably quantitate target sterols, the GC x GC experiment permitted small amounts of sterols and stanols to be detected and separated. Likewise GC-MS analysis was unable to detect some of the minor sterols which coeluted on a single column. The GC x GC mode allows complete separation of several important sterols and stanols, such as 24-ethylcoprostanol, campesterol and 24-methylenecholesterol, demonstrating the enhanced resolving power of the GC x GC system. Separation of 24-ethyl-epi-coprostanol from several algal-derived interfering components was achieved, leading to higher degree of confidence in the quantitative analysis of faecal sterols. The effects of a number of operating variables--column length, carrier flow-rate and elution temperature--on component resolution and presentation of data in the two-column analysis are described. PMID:14650615
Truong, Thy T; Marriott, Philip J; Porter, Nichola A; Leeming, Rhys
Yeast metabolic engineering--targeting sterol metabolism and terpenoid formation.
Terpenoids comprise various structures conferring versatile functions to eukaryotes, for example in the form of prenyl-anchors they attach proteins to membranes. The physiology of eukaryotic membranes is fine-tuned by another terpenoid class, namely sterols. Evidence is accumulating that numerous membrane proteins require specific sterol structural features for function. Moreover, sterols are intermediates in the synthesis of steroids serving as hormones in higher eukaryotes. Like steroids many compounds of the terpenoid family do not contribute to membrane architecture, but serve as signalling, protective or attractant/repellent molecules. Particularly plants have developed a plenitude of terpenoid biosynthetic routes branching off early in the sterol biosynthesis pathway and, thereby, forming one of the largest groups of naturally occurring organic compounds. Many of these aromatic and volatile molecules are interesting for industrial application ranging from foods to pharmaceuticals. Combining the fortunate situation that sterol biosynthesis is highly conserved in eukaryotes with the amenability of yeasts to genetic and metabolic engineering, basically all naturally occurring terpenoids might be produced involving yeasts. Such engineered yeasts are useful for the study of biological functions and molecular interactions of terpenoids as well as for the large-scale production of high-value compounds, which are unavailable in sufficient amounts from natural sources due to their low abundance. PMID:23567752
Wriessnegger, Tamara; Pichler, Harald
Plant Derived Antimalarial Agents: New Leads and Challenges
New treatments for malaria are urgently needed due to the increasing problem of drug-resistance in malaria parasites. The long-established use of quinine and the more recent introduction of artemisinin and its derivatives as highly effective antimalarials demonstrates that plant species are an important resource for the discovery of new antimalarial agents. Furthermore, many plant species continue to be used in
Colin W. Wright
Sterols of the phylum Zygomycota: Phylogenetic implications
The sterol composition of 42 fungal species representing six of the eight orders of the Zygomycota was determined using gas-liquid\\u000a chromatography-mass spectrometry to assess whether the distribution of major sterols in this phylum has taxonomic or phylogenetic\\u000a relevance. Ergosterol, 22-dihydroergosterol, 24-methyl cholesterol, cholesterol, and desmosterol were detected as the major\\u000a sterols among the species studied. Ergosterol was the major sterol
J. D. Weete; S. R. Gandhi
Sterol metabolism in the oomycete Aphanomyces euteiches, a legume root pathogen.
Sterols are isoprenoid-derived molecules that have essential functions in eukaryotes but whose metabolism remains largely unknown in a large number of organisms. Oomycetes are fungus-like microorganisms that are evolutionarily related to stramenopile algae, a large group of organisms for which no sterol metabolic pathway has been reported. Here, we present data that support a model of sterol biosynthesis in Aphanomyces euteiches, an oomycete species causing devastating diseases in legume crops. In silico analyses were performed to identify genes encoding enzymes involved in the conversion of the isoprenoid precursor 3-hydroxy-3-methylglutaryl coenzyme A to isoprenoids. Several metabolic intermediates and two major sterol end-products were identified by gas chromatography-mass spectroscopy. We show that A. euteiches is able to produce fucosterol (a sterol initially identified in brown algae) and cholesterol (the major animal sterol). Mycelium development is inhibited by two sterol demethylase inhibitors used as fungicides, namely tebuconazole and epoxiconazole. We propose the first sterol biosynthetic pathway identified in a stramenopile species. Phylogenetic analyses revealed close relationships between A. euteiches enzyme sequences and those found in stramenopile algae, suggesting that part of this pathway could be conserved in the Stramenopila kingdom. PMID:19496952
Madoui, Mohammed-Amine; Bertrand-Michel, Justine; Gaulin, Elodie; Dumas, Bernard
Sterol components of coral-reef molluscs
The sterol composition of 23 species of coral-reef molluscs from Tahiti was investigated in relation to habitat and taxonomy. The elucidation of sterol components was performed by both argentation column and gas-liquid chromatographic techniques. Coral-reef molluscs, especially gastropods, seem to be characterised by sterols rich in 24-methylcholesterol.
T. Ando; A. Kanazawa; S. Teshima; H. Miyawaki
Potential of gas chromatography-atmospheric pressure chemical ionization-time-of-flight mass spectrometry for the determination of sterols in human plasma.
The application of Gas Chromatography (GC)-Atmospheric Pressure Chemical Ionization (APCI)-Time-of-Flight Mass Spectrometry (TOF-MS) is presented for sterol analysis in human plasma. A commercial APCI interface was modified to ensure a well-defined humidity which is essential for controlled ionization. In the first step, optimization regarding flow rates of auxiliary gases was performed by using a mixture of model analytes. Secondly, the qualitative and quantitative analysis of sterols including oxysterols, cholesterol precursors, and plant sterols as trimethylsilyl-derivatives was successfully carried out. The characteristics of APCI together with the very good mass accuracy of TOF-MS data enable the reliable identification of relevant sterols in complex matrices. Linear calibration lines and plausible results for healthy volunteers and patients could be obtained whereas all mass signals were extracted with an extraction width of 20 ppm from the full mass data set. One advantage of high mass accuracy can be seen in the fact that from one recorded run any search for m/z can be performed. PMID:24463103
Matysik, S; Schmitz, G; Bauer, S; Kiermaier, J; Matysik, F-M
Sterols with antileishmanial activity isolated from the roots of Pentalinon andrieuxii
A new cholesterol derivative, pentalinonsterol (cholest-4,20,24-trien-3-one, 1), and a new polyoxygenated pregnane sterol glycoside, pentalinonside (2), together with 18 known compounds, including 14 sterols (3–16), three coumarins (17–19), and a triterpene (20), were isolated from a n-hexane partition of a methanol extract of the roots of the Mexican medicinal plant Pentalinon andrieuxii. Structure elucidation of compounds 1 and 2 was accomplished by spectroscopic data interpretation. All isolates were evaluated in vitro for their antileishmanial activity. Among these compounds, 6,7-dihydroneridienone (15) was found to be the most potent principle against promastigotes of Leishmania mexicana (L. mexicana). The cholesterol analogue, pentalinonsterol (1), together with two known sterols, 24-methylcholest-4,24(28)-dien-3-one (3) and neridienone (16), also exhibited significant leishmanicidal activity in this same bioassay. Compounds 1, 3, 15, 16, cholest-4-en-3-one (4), and cholest-5,20,24-trien-3?-ol (7), showed strong antileishmanial activity against amastigotes of L. mexicana, and 4 was found to be the most potent agent with an IC50 value of 0.03 ?M. All the isolates were also evaluated for their cytotoxicity in non-infected bone marrow-derived macrophages, but none of these compounds was found active towards this cell line. The intracellular parasites treated with compounds 1, 3, 4, 15, and 16 were further studied by electron microscopy; morphological abnormalities and destruction of the amastigotes were observed, as a result of treatment with these compounds.
Pan, Li; Lezama-Davila, Claudio M.; Isaac-Marquez, Angelica P.; Calomeni, Edward P.; Fuchs, James R.; Satoskar, Abhay R.; Kinghorn, A. Douglas
Competitive solubilization of cholesterol and six species of sterol/stanol in bile salt micelles.
Slight differences in the molecular structures of a category of sterol/stanol species affect the solubility of cholesterol in a bile salt solution. We systematically studied the preferential solubilization of cholesterol and sterol/stanol in sodium taurodeoxycholate solutions using relatively minor plant species of sterol/stanol (brassicasterol and stigmasterol) and a non-plant sterol (cholestanol). As relatively major sterol/stanol species (beta-sitosterol, beta-sitostanol, and campesterol) have already been examined using nearly identical procedures to that used in our system, we were able to sufficiently discuss the cholesterol-lowering effects resulting from the molecular structures of six sterol/stanol species. The results of competitive solubilization revealed that cholestanol has the largest cholesterol-lowering effect, decreasing cholesterol solubility to 33% of that in a single solubilizate system. The molecular structure of cholestanol is also most similar to that of cholesterol. In contrast, brassicasterol and stigmasterol have little ability to decrease cholesterol solubility in a mixed binary system. Both have an unsaturated double bond at the side chain of the steroid ring. By applying thermodynamic analyses to these results, we found that the Gibbs energy changes (DeltaG degrees ) of solubilization for sterol/stanol species with cholesterol-lowering effects show larger negative values than that for cholesterol. PMID:20346931
Matsuoka, Keisuke; Kajimoto, Eriko; Horiuchi, Maho; Honda, Chikako; Endo, Kazutoyo
Plasma non-cholesterol sterols
Increased levels of plasma sterols other than cholesterol can serve as markers for abnormalities in lipid metabolism associated with clinical disease. Premature atherosclerosis and xanthomatosis occur in two rare lipid storage diseases, Cerebrotendinous xanthomatosis (CTX) and sitosterolemia. In CTX, cholestanol is present in all tissues. In sitosterolemia, dietary campesterol and sitosterol accumulate in plasma and red blood cells. Plasma accumulation
A Kuksis
Multiple Functions of Sterols in Yeast Endocytosis
Sterols are essential factors for endocytosis in animals and yeast. To investigate the sterol structural requirements for yeast endocytosis, we created a variety of erg? mutants, each accumulating a distinct set of sterols different from ergosterol. Mutant erg2?erg6? and erg3?erg6? cells exhibit a strong internalization defect of the ?-factor receptor (Ste2p). Specific sterol structures are necessary for pheromone-dependent receptor hyperphosphorylation, a prerequisite for internalization. The lack of phosphorylation is not due to a defect in Ste2p localization or in ligand–receptor interaction. Contrary to most known endocytic factors, sterols seem to function in internalization independently of actin. Furthermore, sterol structures are required at a postinternalization step of endocytosis. erg? cells were able to take up the membrane marker FM4-64, but exhibited defects in FM4-64 movement through endosomal compartments to the vacuole. Therefore, there are at least two roles for sterols in endocytosis. Based on sterol analysis, the sterol structural requirements for these two processes were different, suggesting that sterols may have distinct functions at different places in the endocytic pathway. Interestingly, sterol structures unable to support endocytosis allowed transport of the glycosylphosphatidylinositol-anchored protein Gas1p from the endoplasmic reticulum to Golgi compartment.
Heese-Peck, Antje; Pichler, Harald; Zanolari, Bettina; Watanabe, Reika; Daum, Gunther; Riezman, Howard
Consumption and biochemical impact of commercially available plant-derived nutritional supplements. An observational pilot-study on recreational athletes
Background A growing consumption of natural (plant-derived) dietary supplements with ergogenic aims, with particular regard for ecdysteroids, phytoestrogens and vegetal sterols, has been registered over the last years among "recreational" athletes. The present study was carried out in order to evaluate the real knowledge of plant-derived nutritional supplements among physically active people as well as their real consumption. Additional aim was to evaluate the effects of these supplements on the health profile of the users. Methods Twenty-three trained subjects who habitually used natural dietary supplements, and 30 matched controls were analyzed for plasma biochemical markers and hormonal profile. Results The laboratory tests revealed the absence of any sign of organ toxicity/damage in both athletes and controls. On the contrary, hormone profiles revealed marked alterations in 15 (65%) out of the 23 of investigated athletes. Specifically, 10 males presented increased plasma levels of progesterone, 15 subjects presented abnormal estrogen levels, including 5 (2?F and 3?M) presenting a "dramatic" increased estrogen values and 2 two males with increased estrogen levels, increased testosterone levels and associated suppression of luteinizing hormone and follicle-stimulating hormone. Conclusions The results of the present study highlighted that the habitual consumption of plant-derived nutritional supplements is frequently associated with significant hormonal alterations both in male and female subjects. Although these biochemical alterations were not associated with signs or symptoms of organ toxicity/damage at the moment of the study, it cannot be excluded that, in the mid/long-term, these subjects would suffer of health problems secondary to chronic exposure to heavily altered hormonal levels. Further large scale studies are needed to confirm the results of this pilot study as well as to investigate the biological mechanisms at the base of the observed hormonal alterations.
Regulation of Sterol Content in Membranes by Subcellular Compartmentation of Steryl-Esters Accumulating in a Sterol-Overproducing Tobacco Mutant.
The study of sterol overproduction in tissues of LAB 1-4 mutant tobacco (Nicotiana tabacum L. cv Xanthi) (P. Maillot-Vernier, H. Schaller, P. Benveniste, G. Belliard [1989] Biochem Biophys Res Commun 165: 125-130) over several generations showed that the overproduction phenotype is stable in calli, with a 10-fold stimulation of sterol content when compared with wild-type calli. However, leaves of LAB 1-4 plants obtained after two steps of self-fertilization were characterized by a mere 3-fold stimulation, whereas calli obtained from these plants retained a typical sterol-overproducing mutant phenotype (i.e. a 10-fold increase of sterol content). These results suggest that the expression of the LAB 1-4 phenotype is dependent on the differentiation state of cells. Most of the sterols accumulating in the mutant tissues were present as steryl-esters, which were minor species in wild-type tissues. Subcellular fractionation showed that in both mutant and wild-type tissues, free sterols were associated mainly with microsomal membranes. In contrast, the bulk of steryl-esters present in mutant tissues was found in the soluble fraction of cells. Numerous lipid droplets were detected in the hyaloplasm of LAB 1-4 cells by cytochemical and cytological techniques. After isolation, these lipid granules were shown to contain steryl-esters. These results show that the overproduced sterols of mutant tissues accumulate as steryl-esters in hyaloplasmic bodies. The esterification process thus allows regulation of the amount of free sterols in membranes by subcellular compartmentation.
Gondet, L.; Bronner, R.; Benveniste, P.
Plant-derived virus-like particles as vaccines.
Virus-like particles (VLPs) are self-assembled structures derived from viral antigens that mimic the native architecture of viruses but lack the viral genome. VLPs have emerged as a premier vaccine platform due to their advantages in safety, immunogenicity, and manufacturing. The particulate nature and high-density presentation of viral structure proteins on their surface also render VLPs as attractive carriers for displaying foreign epitopes. Consequently, several VLP-based vaccines have been licensed for human use and achieved significant clinical and economical success. The major challenge, however, is to develop novel production platforms that can deliver VLP-based vaccines while significantly reducing production times and costs. Therefore, this review focuses on the essential role of plants as a novel, speedy and economical production platform for VLP-based vaccines. The advantages of plant expression systems are discussed in light of their distinctive posttranslational modifications, cost-effectiveness, production speed, and scalability. Recent achievements in the expression and assembly of VLPs and their chimeric derivatives in plant systems as well as their immunogenicity in animal models are presented. Results of human clinical trials demonstrating the safety and efficacy of plant-derived VLPs are also detailed. Moreover, the promising implications of the recent creation of "humanized" glycosylation plant lines as well as the very recent approval of the first plant-made biologics by the U. S. Food and Drug Administration (FDA) for plant production and commercialization of VLP-based vaccines are discussed. It is speculated that the combined potential of plant expression systems and VLP technology will lead to the emergence of successful vaccines and novel applications of VLPs in the near future. PMID:22995837
Chen, Qiang; Lai, Huafang
Fluorescent in situ visualization of sterols in Arabidopsis roots
Sterols are eukaryotic membrane components with crucial roles in diverse cellular processes. Elucidation of sterol function relies on development of tools for in situ sterol visualization. Here we describe protocols for in situ sterol localization in Arabidopsis thaliana root cells, using filipin as a specific probe for detection of fluorescent filipin-sterol complexes. Currently, filipin is the only established tool for
Yohann Boutté; Shuzhen Men; Markus Grebe
Herbal remedies of the maritime Indians: Sterols and triterpenes of Tanacetum vulgare L. (Tansy)
Plant sterols and triterpenes exhibit a wide range of pharmacological activities. As part of our ongoing studies of the medicinal\\u000a aspects of Maritime flora, particularly the herbal remedies of the Micmac and Malecite Indians, we determined the nature of\\u000a the sterols and triterpenes ofTanacetum vulgare L. (Compositae)—a widely used herbal remedy usually referred to as tansy. By using thin layer
R. F. Chandler; S. N. Hooper; D. L. Hooper; W. D. Jamieson; E. Lewis
Occurrence of 24( E )-ethylidene sterols in two solanaceae seed oils and rice bran oil
The occurrence of two 24 (E)-ethylidene sterols, fucosterol and 28-isocitrostadienol, in the unsaponifiable matters of two Solanaceae seed oils fromDatura stramonium andCapsicum annuum, and rice bran oil from the seeds ofOryza sativa (Gramineae) was demonstrated by their isolation or by gas liquid chromatography. AlthoughZ-isomers of the above two 24-ethylidene sterols, 28-isofucosterol and citrostadienol, are a frequent occurrence in higher\\u000a plant
Toshihiro Itoh; Suguru Sakurai; Toshitake Tamura; Taro Matsumoto
Plant amino acid-derived vitamins: biosynthesis and function.
Vitamins are essential organic compounds for humans, having lost the ability to de novo synthesize them. Hence, they represent dietary requirements, which are covered by plants as the main dietary source of most vitamins (through food or livestock's feed). Most vitamins synthesized by plants present amino acids as precursors (B1, B2, B3, B5, B7, B9 and E) and are therefore linked to plant nitrogen metabolism. Amino acids play different roles in their biosynthesis and metabolism, either incorporated into the backbone of the vitamin or as amino, sulfur or one-carbon group donors. There is a high natural variation in vitamin contents in crops and its exploitation through breeding, metabolic engineering and agronomic practices can enhance their nutritional quality. While the underlying biochemical roles of vitamins as cosubstrates or cofactors are usually common for most eukaryotes, the impact of vitamins B and E in metabolism and physiology can be quite different on plants and animals. Here, we first aim at giving an overview of the biosynthesis of amino acid-derived vitamins in plants, with a particular focus on how this knowledge can be exploited to increase vitamin contents in crops. Second, we will focus on the functions of these vitamins in both plants and animals (and humans in particular), to unravel common and specific roles for vitamins in evolutionary distant organisms, in which these amino acid-derived vitamins play, however, an essential role. PMID:24368523
Miret, Javier A; Munné-Bosch, Sergi
Plant-derived pharmaceuticals for the developing world.
Plant-produced vaccines and therapeutic agents offer enormous potential for providing relief to developing countries by reducing the incidence of infant mortality caused by infectious diseases. Vaccines derived from plants have been demonstrated to effectively elicit an immune response. Biopharmaceuticals produced in plants are inexpensive to produce, require fewer expensive purification steps, and can be stored at ambient temperatures for prolonged periods of time. As a result, plant-produced biopharmaceuticals have the potential to be more accessible to the rural poor. This review describes current progress with respect to plant-produced biopharmaceuticals, with a particular emphasis on those that target developing countries. Specific emphasis is given to recent research on the production of plant-produced vaccines toward human immunodeficiency virus, malaria, tuberculosis, hepatitis B virus, Ebola virus, human papillomavirus, rabies virus and common diarrheal diseases. Production platforms used to express vaccines in plants, including nuclear and chloroplast transformation, and the use of viral expression vectors, are described in this review. The review concludes by outlining the next steps for plant-produced vaccines to achieve their goal of providing safe, efficacious and inexpensive vaccines to the developing world. PMID:23857915
Hefferon, Kathleen
Analysis of unsaturated c27 sterols by nuclear magnetic resonance spectroscopy
Complete 'H and IsC nuclear magnetic reso- nance (NMR) signal assignments have been established for 5a-cholestan-3P-01, 22 unsaturated C27 sterols, and their ace- tate derivatives. Assignments were made from a combination of 1D and 2D spectra and include stereochemical 'H assign- ments for the C-22 and C-23 protons of 5a-cholesta-8,24dien- 3p-01 and other A*' sterols with a Cg side chain.
William K. Wilson; Rhea M. Sumpter; Joshua J. Warren; Peter S. Rogers; Benfang Ruan; George J. Schroepfer
The content and composition of sterols and sterol esters in sunflower and poppy seed oils
The composition and proportion of free sterols and sterol esters in crude sunflower and poppy seed oils were determined, using\\u000a preparative thin layer chromatography followed by gas chromatography with cholesterol as an internal standard. Free sterols\\u000a and sterol esters were also isolated in a liquid fraction obtained by low temperature crystallization (?80 C) of the oils\\u000a and enriched with minor
Anna Johansson
Response of ?? T cells to plant-derived tannins
Many pharmaceutical drugs are isolated from plants used in traditional medicines. Through screening plant extracts, both traditional medicines and compound libraries, new pharmaceutical drugs continue to be identified. Currently, two plant-derived agonists for ?? T cells are described. These plant-derived agonists impart innate effector functions upon distinct ?? T cell subsets. Plant tannins represent one class of ?? T cell agonist and preferentially activate the mucosal population. Mucosal ?? T cells function to modulate tissue immune responses and induce epithelium repair. Select tannins, isolated from apple peel, rapidly induce immune gene transcription in ?? T cells, leading to cytokine production and increased responsiveness to secondary signals. Activity of these tannin preparations tracks to the procyanidin fraction, with the procyanidin trimer (C1) having the most robust activity defined to date. The response to the procyanidins is evolutionarily conserved in that responses are seen with human, bovine, and murine ?? T cells. Procyanidin-induced responses described in this review likely account for the expansion of mucosal ?? T cells seen in mice and rats fed soluble extracts of tannins. Procyanidins may represent a novel approach for treatment of tissue damage, chronic infection, and autoimmune therpies.
Holderness, Jeff; Hedges, Jodi F.; Daughenbaugh, Katie; Kimmel, Emily; Graff, Jill; Freedman, Brett; Jutila, Mark A.
Approaches to the Analysis of Plant-Derived Natural Products
The term "plant-derived natural product" is extremely broad and the scope of this chapter is determined by the nature of lower-abundance\\u000a secondary metabolites rather than storage proteins, starch, cell walls, and lipids. In some instances, however, similar techniques\\u000a can used to measure both groups of compounds. The bioactivity of secondary metabolites underlines their importance in human\\u000a nutrition, health, pharmacy and
Lionel Hill; Trevor L. Wang
Cameroonian Medicinal Plants: Pharmacology and Derived Natural Products
Many developing countries including Cameroon have mortality patterns that reflect high levels of infectious diseases and the risk of death during pregnancy and childbirth, in addition to cancers, cardiovascular diseases and chronic respiratory diseases that account for most deaths in the developed world. Several medicinal plants are used traditionally for their treatment. In this review, plants used in Cameroonian traditional medicine with evidence for the activities of their crude extracts and/or derived products have been discussed. A considerable number of plant extracts and isolated compounds possess significant antimicrobial, anti-parasitic including antimalarial, anti-proliferative, anti-inflammatory, anti-diabetes, and antioxidant effects. Most of the biologically active compounds belong to terpenoids, phenolics, and alkaloids. Terpenoids from Cameroonian plants showed best activities as anti-parasitic, but rather poor antimicrobial effects. The best antimicrobial, anti-proliferative, and antioxidant compounds were phenolics. In conclusion, many medicinal plants traditionally used in Cameroon to treat various ailments displayed good activities in vitro. This explains the endeavor of Cameroonian research institutes in drug discovery from indigenous medicinal plants. However, much work is still to be done to standardize methodologies and to study the mechanisms of action of isolated natural products.
Kuete, Victor; Efferth, Thomas
Investigating the allosterism of acyl-CoA:cholesterol acyltransferase (ACAT) by using various sterols: in vitro and intact cell studies
ACAT1 (acyl-CoA:cholesterol acyltransferase 1) is thought to have two distinct sterol-binding sites: a substrate-binding site and an allosteric-activator site. In the present work, we investigated the structural features of various sterols as substrates and\\/or activ- ators in vitro. The results show that without cholesterol, the plant sterol sitosterol is a poor substrate for ACAT. In the presence of cholesterol, ACAT1-mediated
Jay Liu; Ta-Yuan Chang
Andrographolide: A New Plant-Derived Antineoplastic Entity on Horizon
Plant-derived natural products occupy an important position in the area of cancer chemotherapy. Molecules such as vincristine, vinblastine, paclitaxel, camptothecin derivatives, epipodophyllotoxin, and so forth, are invaluable contributions of nature to modern medicine. However, the quest to find out novel therapeutic compounds for cancer treatment and management is a never-ending venture; and diverse plant species are persistently being studied for identification of prospective anticancer agents. In this regard, Andrographis paniculata Nees, a well-known plant of Indian and Chinese traditional system of medicines, has drawn attention of researchers in recent times. Andrographolide, the principal bioactive chemical constituent of the plant has shown credible anticancer potential in various investigations around the globe. In vitro studies demonstrate the capability of the compound of inducing cell-cycle arrest and apoptosis in a variety of cancer cells at different concentrations. Andrographolide also shows potent immunomodulatory and anti-angiogenic activities in tumorous tissues. Synthetic analogues of the compound have also been created and analyzed, which have also shown similar activities. Although it is too early to predict its future in cancer chemotherapy, the prologue strongly recommends further research on this molecule to assess its potential as a prospective anticancer agent.
Varma, Astha; Padh, Harish; Shrivastava, Neeta
Overview of Major Classes of Plant-Derived Anticancer Drugs
Cancer is the second leading cause of death worldwide. Conventional cancer therapies cause serious side effects and, at best, merely extend the patient's lifespan by a few years. Cancer control may therefore benefit from the potential that resides in alternative therapies. The demand to utilize alternative concepts or approaches to the treatment of cancer is therefore escalating. There is compelling evidence from epidemiological and experimental studies that highlight the importance of compounds derived from plants "phytochemicals" to reduce the risk of colon cancer and inhibit the development and spread of tumors in experimental animals. More than 25% of drugs used during the last 20 years are directly derived from plants, while the other 25% are chemically altered natural products. Still, only 5-15% of the approximately 250,000 higher plants have ever been investigated for bioactive compounds. The advantage of using such compounds for cancer treatment is their relatively non-toxic nature and availability in an ingestive form. An ideal phytochemical is one that possesses anti-tumor properties with minimal toxicity and has a defined mechanism of action. As compounds that target specific signaling pathways are identified, researchers can envisage novel therapeutic approaches as well as a better understanding of the pathways involved in disease progression. Here, we focus on 4 classes of natural anticancer drugs: methyltransferase inhibitors, DNA damaging/pro-oxidant drugs, HDAC inhibitors (HDACi), and mitotic disrupters, and we will focus on the mode of action for one promising example per group.
Amin, Amr; Gali-Muhtasib, Hala; Ocker, Matthias; Schneider-Stock, Regine
Sterol phylogenesis and algal evolution
The stereochemistry of several sterol precursors and end products synthesized by two fungal-like microorganisms Prototheca wickerhamii (I) and Dictyostelium discoideum (II) have been determined by chromatographic (TLC, GLC, and HPLC) and spectral (UV, MS, and {sup 1}H NMR) methods. From I and II the following sterols were isolated from the cells: cycloartenol, cyclolaudenol, 24(28)-methylenecy-cloartanol, ergosterol, protothecasterol, 4{alpha}-methylergostanol, 4{alpha}-methylclionastanol, clionastanol, 24{beta}-ethylcholesta-8,22-enol, and dictyosterol. In addition, the mechanism of C-24 methylation was investigated in both organisms by feeding to I (2-{sup 3}H)lanosterol, (2-{sup 3}H)cycloartenol, (24{sup 3}H)lanosterol, and (methyl-{sup 2}H{sub 3})methionine and by feeding to II (methyl-{sup 2}H{sub 3})methionine. The results demonstrate that the 24{beta} configuration is formed by different alkylation routes in I and II. The authors conclude that Prototheca is an apoplastic Chlorella (i.e., an alga) and that Dictyostelium as well as the other soil amoebae that synthesize cycloartenol evolved from algal rather than fungal ancestors.
Nes, W.D.; Norton, R.A.; Crumley, F.G. (Richard B. Russell Research Center, Athens, GA (USA)); Madigan, S.J.; Katz, E.R. (State Univ. of New York at Stony Brook (USA))
Tracking plant-derived biomarkers from source to sink in the Miners River, Upper Peninsula of Michigan (USA)
NASA Astrophysics Data System (ADS)
Biogeochemical cycling of terrestrial organic matter and it subsequent burial plays a vital role in the global carbon cycle. Rivers provide a pathway for terrestrial organic carbon dispersal and integration into sediments. Terrestrial plant biomarkers are useful tools for studying carbon cycling because they can provide an indication of the source of organic carbon in both modern and ancient sediments. Biomarkers can also be used as paleovegetation proxies in geologic sediments where fossils are absent. However, limited information is available about the dispersal and deposition of plant biomarkers in modern river systems, especially for compounds that provide taxonomic specificity such as di- and triterpenoids (diagnostic for conifers and angiosperms, respectively). To better resolve the modes of biomarker transport within fluvial and riparian systems, we characterized plant biomarker transport in the Miners River, a small river basin within a mixed angiosperm-conifer forest at Pictured Rocks National Lakeshore (MI, USA). To assess the transport of biomarkers in river systems, we collected plants, soils, river sediments, and filtered particulate and dissolved organic carbon from seven sites from the headwaters to Lake Superior along the Miners River (~20 km pathway). All samples contained long-chain n-alkyl lipids, sterols, diterpenoids (abietane and pimarane classes), and triterpenoids (oleanane, ursane, and lupane classes). With the exception of a soil sample taken at a depth of 30 cm, triterpenoids are found in higher concentrations than diterpenoids in riparian soils and river sediments. Biomarker compositions in riparian soils, point bar, and overbank deposits are similar to the surrounding vegetation, albeit much lower in concentration. The composition of di- and triterpenoids in the river-suspended particulate organic carbon is similar in composition to the surrounding vegetation and soils. We developed a method to isolate biomarkers in the dissolved organic carbon fraction in river waters using solid-phase extraction and the preliminary data suggests that di- and triterpenoids are transported as dissolved organic carbon, however concentrations are lower than in the particulate organic carbon fraction. Results from the Miners River will help to better define terrestrial organic matter cycling in small river catchments. Characterizing how plant biomarkers are transported in river systems will enhance our interpretations of plant biomarkers in the geologic record. This will provide new insights into biomarker transport and potential source/sink biases in fluvial systems and thus identify potential complications for using plant-derived biomarkers as quantitative paleovegetation indicators and will enhance the use of biomarker-specific isotope analyses.
Giri, S. J.; Diefendorf, A. F.; Lowell, T. V.
Survey of extrachromosomal circular DNA derived from plant satellite repeats
Background Satellite repeats represent one of the most dynamic components of higher plant genomes, undergoing rapid evolutionary changes of their nucleotide sequences and abundance in a genome. However, the exact molecular mechanisms driving these changes and their eventual regulation are mostly unknown. It has been proposed that amplification and homogenization of satellite DNA could be facilitated by extrachromosomal circular DNA (eccDNA) molecules originated by recombination-based excision from satellite repeat arrays. While the models including eccDNA are attractive for their potential to explain rapid turnover of satellite DNA, the existence of satellite repeat-derived eccDNA has not yet been systematically studied in a wider range of plant genomes. Results We performed a survey of eccDNA corresponding to nine different families and three subfamilies of satellite repeats in ten species from various genera of higher plants (Arabidopsis, Oryza, Pisum, Secale, Triticum and Vicia). The repeats selected for this study differed in their monomer length, abundance, and chromosomal localization in individual species. Using two-dimensional agarose gel electrophoresis followed by Southern blotting, eccDNA molecules corresponding to all examined satellites were detected. EccDNA occurred in the form of nicked circles ranging from hundreds to over eight thousand nucleotides in size. Within this range the circular molecules occurred preferentially in discrete size intervals corresponding to multiples of monomer or higher-order repeat lengths. Conclusion This work demonstrated that satellite repeat-derived eccDNA is common in plant genomes and thus it can be seriously considered as a potential intermediate in processes driving satellite repeat evolution. The observed size distribution of circular molecules suggests that they are most likely generated by molecular mechanisms based on homologous recombination requiring long stretches of sequence similarity.
Navratilova, Alice; Koblizkova, Andrea; Macas, Jiri
In Vitro and In Vivo Anticancer Effects of Sterol Fraction from Red Algae Porphyra dentata.
Porphyra dentata, an edible red macroalgae, is used as a folk medicine in Asia. This study evaluated in vitro and in vivo the protective effect of a sterol fraction from P. dentata against breast cancer linked to tumor-induced myeloid derived-suppressor cells (MDSCs). A sterol fraction containing cholesterol, ? -sitosterol, and campesterol was prepared by solvent fractionation of methanol extract of P. dentata??in silica gel column chromatography. This sterol fraction in vitro significantly inhibited cell growth and induced apoptosis in 4T1 cancer cells. Intraperitoneal injection of this sterol fraction at 10 and 25?mg/kg body weight into 4T1 cell-implanted tumor BALB/c mice significantly inhibited the growth of tumor nodules and increased the survival rate of mice. This sterol fraction significantly decreased the reactive oxygen species (ROS) and arginase activity of MDSCs in tumor-bearing mice. Therefore, the sterol fraction from P. dentata showed potential for protecting an organism from 4T1 cell-based tumor genesis. PMID:24062783
Kaz?owska, Katarzyna; Lin, Hong-Ting Victor; Chang, Shun-Hsien; Tsai, Guo-Jane
Overall Plant Design Description (OPDD) Coal Derived Liquid Electric Power Plant.
National Technical Information Service (NTIS)
The Case C power plant fueled with coal-derived liquid (CDL) fuel generates 443,500 kW of electrical power with an overall thermal efficiency of 48.66 percent based on higher heating value coal liquid to busbar. (The CDL manufacturing cycle is 67 percent ...
Diet micronutrient balance matters: How the ratio of dietary sterols/steroids affects development, growth and reproduction in two lepidopteran insects.
Insects lack the ability to synthesize sterols de novo so they acquire this essential nutrient from their food. Cholesterol is the dominant sterol found in most insects, but in plant vegetative tissue it makes up only a small fraction of the total sterol profile. Instead, plants mostly contain phytosterols; plant-feeding insects generate the majority of their cholesterol by metabolizing phytosterols. However, not all phytosterols are readily converted to cholesterol, and some are even deleterious when ingested above a threshold level. In a recent study we showed that caterpillars reared on tobacco accumulating novel sterols/steroids exhibited reduced performance, even when suitable sterols were present. In the current study we examined how the dominant sterols (cholesterol and stigmasterol) and steroids (cholestanol and cholestanone) typical of the modified tobacco plants affected two insect herbivores (Heliothis virescens and Helicoverpa zea). The sterols/steroids were incorporated into synthetic diets singly, as well as in various combinations, ratios and amounts. For each insect species, a range of performance values was recorded for two generations, with the eggs from the 1st-generation adults as the source of neonates for the 2nd-generation. Performance on the novel steroids (cholestanol and cholestanone) was extremely poor compared to suitable sterols (cholesterol and stigmasterol). Additionally, performance tended to decrease as the ratio of the novel dietary steroids increased. We discuss how the balance of different dietary sterols/steroids affected our two caterpillar species, relate this back to recent studies on sterol/steroid metabolism in these two species, and consider the potential application of sterol/steroid modification in crops. PMID:24953330
Jing, Xiangfeng; Grebenok, Robert J; Behmer, Spencer T
Intracellular sterol transport in eukaryotes, a connection to mitochondrial function?
Eukaryotic cells synthesize sterols in the endoplasmatic reticulum (ER) from where it needs to be efficiently transported to the plasma membrane, which harbors ?90% of the free sterol pool of the cell. Sterols that are being taken up from the environment, on the other hand, are transported back from the plasma membrane to the ER, where the free sterols are
Roger Schneiter
Impaired sterol ester synthesis alters the response of Arabidopsis thaliana to Phytophthora infestans.
Non-host resistance of Arabidopsis thaliana against Phytophthora infestans, the causal agent of late blight disease of potato, depends on efficient extracellular pre- and post-invasive resistance responses. Pre-invasive resistance against P. infestans requires the myrosinase PEN2. To identify additional genes involved in non-host resistance to P. infestans, a genetic screen was performed by re-mutagenesis of pen2 plants. Fourteen independent mutants were isolated that displayed an enhanced response to Phytophthora (erp) phenotype. Upon inoculation with P. infestans, two mutants, pen2-1 erp1-3 and pen2-1 erp1-4, showed an enhanced rate of mesophyll cell death and produced excessive callose deposits in the mesophyll cell layer. ERP1 encodes a phospholipid:sterol acyltransferase (PSAT1) that catalyzes the formation of sterol esters. Consistent with this, the tested T-DNA insertion lines of PSAT1 are phenocopies of erp1 plants. Sterol ester levels are highly reduced in all erp1/psat1 mutants, whereas sterol glycoside levels are increased twofold. Excessive callose deposition occurred independently of PMR4/GSL5 activity, a known pathogen-inducible callose synthase. A similar formation of aberrant callose deposits was triggered by the inoculation of erp1 psat1 plants with powdery mildew. These results suggest a role for sterol conjugates in cell non-autonomous defense responses against invasive filamentous pathogens. PMID:23072470
Kopischke, Michaela; Westphal, Lore; Schneeberger, Korbinian; Clark, Richard; Ossowski, Stephan; Wewer, Vera; Fuchs, René; Landtag, Jörn; Hause, Gerd; Dörmann, Peter; Lipka, Volker; Weigel, Detlef; Schulze-Lefert, Paul; Scheel, Dierk; Rosahl, Sabine
Sterols in spermatogenesis and sperm maturation
Mammalian spermatogenesis is a complex developmental program in which a diploid progenitor germ cell transforms into highly specialized spermatozoa. One intriguing aspect of sperm production is the dynamic change in membrane lipid composition that occurs throughout spermatogenesis. Cholesterol content, as well as its intermediates, differs vastly between the male reproductive system and nongonadal tissues. Accumulation of cholesterol precursors such as testis meiosis-activating sterol and desmosterol is observed in testes and spermatozoa from several mammalian species. Moreover, cholesterogenic genes, especially meiosis-activating sterol-producing enzyme cytochrome P450 lanosterol 14?-demethylase, display stage-specific expression patterns during spermatogenesis. Discrepancies in gene expression patterns suggest a complex temporal and cell-type specific regulation of sterol compounds during spermatogenesis, which also involves dynamic interactions between germ and Sertoli cells. The functional importance of sterol compounds in sperm production is further supported by the modulation of sterol composition in spermatozoal membranes during epididymal transit and in the female reproductive tract, which is a prerequisite for successful fertilization. However, the exact role of sterols in male reproduction is unknown. This review discusses sterol dynamics in sperm maturation and describes recent methodological advances that will help to illuminate the complexity of sperm formation and function.
Keber, Rok; Rozman, Damjana; Horvat, Simon
Plant-Derived Human Collagen Scaffolds for Skin Tissue Engineering
Tissue engineering scaffolds are commonly formed using proteins extracted from animal tissues, such as bovine hide. Risks associated with the use of these materials include hypersensitivity and pathogenic contamination. Human-derived proteins lower the risk of hypersensitivity, but possess the risk of disease transmission. Methods engineering recombinant human proteins using plant material provide an alternate source of these materials without the risk of disease transmission or concerns regarding variability. To investigate the utility of plant-derived human collagen (PDHC) in the development of engineered skin (ES), PDHC and bovine hide collagen were formed into tissue engineering scaffolds using electrospinning or freeze-drying. Both raw materials were easily formed into two common scaffold types, electrospun nonwoven scaffolds and lyophilized sponges, with similar architectures. The processing time, however, was significantly lower with PDHC. PDHC scaffolds supported primary human cell attachment and proliferation at an equivalent or higher level than the bovine material. Interleukin-1 beta production was significantly lower when activated THP-1 macrophages where exposed to PDHC electrospun scaffolds compared to bovine collagen. Both materials promoted proper maturation and differentiation of ES. These data suggest that PDHC may provide a novel source of raw material for tissue engineering with low risk of allergic response or disease transmission.
Willard, James J.; Drexler, Jason W.; Das, Amitava; Roy, Sashwati; Shilo, Shani; Shoseyov, Oded
Sterol carrier protein-2 stimulates intermembrane sterol transfer by direct membrane interaction
It is unclear how the cytosolic sterol carrier protein-2 (SCP-2) binds sterols and enhances sterol transfer between membranes. Therefore, human recombinant SCP-2 was used in conjunction with phase fluorometry, dialysis, and chemical labeling techniques to show if a direct membrane effect accounted for this activity. SCP-2 directly interacted with L-cell fibroblast plasma membrane vesicles as determined by increased fluorescence anisotropy
Judith K. Woodford; Scott M. Colles; Sean Myers-Payne; Jeffrey T. Billheimerb; Friedhelm Schroeder
Plant extracts and plant-derived compounds: promising players in a countermeasure strategy against radiological exposure.
Radiation exposure leads to several pathophysiological conditions, including oxidative damage, inflammation and fibrosis, thereby affecting the survival of organisms. This review explores the radiation countermeasure properties of fourteen (14) plant extracts or plant-derived compounds against these cellular manifestations. It was aimed at evaluating the possible role of plants or its constituents in radiation countermeasure strategy. All the 14 plant extracts or compounds derived from it and considered in this review have shown some radioprotection in different in vivo, ex-vivo and or in vitro models of radiological injury. However, few have demonstrated advantages over the others. C. majus possessing antioxidant, anti-inflammatory and immunomodulatory effects appears to be promising in radioprotection. Its crude extracts as well as various alkaloids and flavonoids derived from it, have shown to enhance survival rate in irradiated mice. Similarly, curcumin with its antioxidant and the ability to ameliorate late effect of radiation exposure, combined with improvement in survival in experimental animal following irradiation, makes it another probable candidate against radiological injury. Furthermore, the extracts of P. hexandrum and P. kurroa in combine treatment regime, M. piperita, E. officinalis, A. sinensis, nutmeg, genistein and ginsan warrants further studies on their radioprotective potentials. However, one that has received a lot of attention is the dietary flaxseed. The scavenging ability against radiation-induced free radicals, prevention of radiation-induced lipid peroxidation, reduction in radiation cachexia, level of inflammatory cytokines and fibrosis, are some of the remarkable characteristics of flaxseed in animal models of radiation injury. While countering the harmful effects of radiation exposure, it has shown its ability to enhance survival rate in experimental animals. Further, flaxseed has been tested and found to be equally effective when administered before or after irradiation, and against low doses (? 5 Gy) to the whole body or high doses (12-13.5 Gy) to the whole thorax. This is particularly relevant since apart from the possibility of using it in pre-conditioning regime in radiotherapy, it could also be used during nuclear plant leakage/accidents and radiological terrorism, which are not pre-determined scenarios. However, considering the infancy of the field of plant-based radioprotectors, all the above-mentioned plant extracts/plant-derived compounds deserves further stringent study in different models of radiation injury. PMID:24761841
Kma, Lakhan
Fibroblast membrane sterol kinetic domains: modulation by sterol carrier protein-2 and liver fatty acid binding protein
The mechanism(s) of intracellular sterol traffick- ing among subcellular organelle membranes is not well un- derstood. Relative contributions of vesicular, sterol carrier protein, and membrane sterol domain pathways are not re- solved. A sterol kinetic assay was used to resolve multiple sterol domains in microsome (MICRO), mitochondria (MITO), and plasma (PM) membrane: exchangeable, 20-40% of total; non-exchangeable, 60-80% of total.
Andrey Frolov; Judith K. Woodford; Eric J. Murphy; Jeffrey T. Billheher; Friedhelm Schroederl
Fruit and vegetative characteristics of endosperm-derived kiwifruit (Actinidia chinensis F) plants
Four hundred and thirty-eight endosperm-derived plants of kiwifruit (Actinidia chinensis) were observed. The plants were field planted in 1982 and all had flowered annually since 1986. A sample of these plants was assessed for leaf morphology, growth characteristics, flowering, sex expression, chromosome number, and fruit quality characteristics. The chromosome number of the endosperm plants varied from 58 to 146; most
Y. Gui; S. Hong; S. Ke; R. M. Skirvin
Universal Behavior of Membranes with Sterols
Lanosterol is the biosynthetic precursor of cholesterol and ergosterol, sterols that predominate in the membranes of mammals and lower eukaryotes, respectively. These three sterols are structurally quite similar, yet their relative effects on membranes have been shown to differ. Here we study the effects of cholesterol, lanosterol, and ergosterol on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipid bilayers at room temperature. Micropipette aspiration is used
J. Henriksen; A. C. Rowat; Y. W. Hsueh; J. L. Thewalt; M. J. Zuckermann; J. H. Ipsen
Distribution of fecal sterols in surface sediment of Sungai Tebrau, Johor
NASA Astrophysics Data System (ADS)
Decreasing quality of aquatic environments may harm human health in general. Sewage pollution from human and animal excretions is a major cause of environmental quality depletion. This study investigates the distribution of sewage contamination level in twenty surface sediment samples taken from Sungai Tebrau, Johor. Four principal fecal sterols have been identified and were found in all sediment samples, which are coprostanol, cholesterol, epicoprostanol and also cholestanol. Cholesterol as the major sterol and most abundant compound derived from a variety of sources ranged from 32.92 to 1,100.55 ngg-1 dry weights. Meanwhile, major fecal sterol, coprostanol has the lowest quantity of total sterol in all samples, constituting only 13% of total sterol. It ranged from 12.63 to 565.42 ngg-1 dry weights, but only two stations (ST12 and ST14) are sewage contaminated. Squatters and residential areas are a major contributor of poorly treated sewage into the aquatic environment. Coprostanol concentration alone is not reliable to indicate sewage contamination; diagnostic indices enhance reliability of sterols as a marker for sewage contamination. Indices applied in this study are coprostanol/cholesterol, coprostanol/(coprostanol+cholestanol) and also epicoprostanol/coprostanol. Resultsof coprostanol/cholesterol, coprostanol/(coprostanol+cholestanol) indices supported the findings that both ST12 and ST14 samples are contaminated with sewage. All samples consist of relativelyhigh concentration of epicoprostanol and high ratio value of epicoprostanol/coprostanol. Generally, it can be concluded that these sampling sites are not contaminated with sewage even though fecal sterols were detected in all samples as they were found to be at low concentration.
Nordin, N.; Ali, M. M.
Lectin cDNA and transgenic plants derived therefrom
Transgenic plants containing cDNA encoding Gramineae lectin are described. The plants preferably contain cDNA coding for barley lectin and store the lectin in the leaves. The transgenic plants, particularly the leaves exhibit insecticidal and fungicidal properties.
Raikhel, Natasha V. (Okemos, MI)
Advances in analytical methods to study cholesterol metabolism: the determination of serum noncholesterol sterols.
Cholesterol biosynthesis precursors and plant sterols are noncholesterol sterols currently used as relative surrogate markers of cholesterol synthesis and absorption, respectively. Its determination in serum samples is a way of diagnosing inherited disorders and also a tool for health evaluation during lipid-lowering lifestyle/drug therapy monitoring. This approach is the only one that can be used for large-scale clinical trials or population based studies, but, nevertheless, there is no reference method for the quantification of noncholesterol sterols in human serum samples and only analysis by GC-FID and GC-MS has been reported to be completely validated. Although there has been a wider use of noncholesterol sterols for the measurement and characterization of cholesterol metabolism, there is a lack of harmonization of measurements and of standardization of the methodology, which is essential for routine measurements of diagnostic utility. New recent advances in analytical methods for the determination of serum noncholesterol sterols are highlighted, focusing on the sample preparation, separation and detection techniques, which will enhance the range of applications in clinical practice. PMID:23165328
Andrade, Isabel; Santos, Lčlita; Ramos, Fernando
Assessing anthropogenic contamination in surface sediments of Niger Delta, Nigeria with fecal sterols and n-alkanes as indicators.
The occurrence of sterols and n-alkanes in surface sediments from rivers and canals in the Niger Delta, Nigeria, determined with a gas chromatography-mass spectrometry method, was used to assess the impacts of anthropogenic activities in the area. The concentrations of total sterols (??Sterol) and n-alkanes (???n-alkane) in the sediments ranged from 133 to 2040 ng/g and 474 to 79,200 ng/g, respectively. An evaluation of the source diagnostic indices indicated that petroleum related sources (petrogenic) were the main contributor of n-alkanes in the samples, with minor contribution from higher plants waxes (biogenic), while the sterols were mainly of biogenic origin. The ratio of ?-cholestanone/(?-cholestanone+?-cholestanone), a commonly used source diagnostic index, implicated no fecal contamination in most of the sediment samples under investigation. These results have established the occurrence of anthropogenic contamination in Niger Delta sediments with significant contributions from petrogenic sources. PMID:23137973
Sojinu, Samuel O; Sonibare, Oluwadayo O; Ekundayo, O; Zeng, Eddy Y
Cloning and characterization of ERG25, the Saccharomyces cerevisiae gene encoding C-4 sterol methyl oxidase.
We have cloned the Saccharomyces cerevisiae C-4 sterol methyl oxidase ERG25 gene. The sterol methyl oxidase performs the first of three enzymic steps required to remove the two C-4 methyl groups leading to cholesterol (animal), ergosterol (fungal), and stigmasterol (plant) biosynthesis. An ergosterol auxotroph, erg25, which fails to demethylate and concomitantly accumulates 4,4-dimethylzy-mosterol, was isolated after mutagenesis. A complementing clone consisting of a 1.35-kb Dra I fragment encoded a 309-amino acid polypeptide (calculated molecular mass, 36.48 kDa). The amino acid sequence shows a C-terminal endoplasmic reticulum retrieval signal KKXX and three histidine-rich clusters found in eukaryotic membrane desaturases and in a bacterial alkane hydroxylase and xylene monooxygenase. The sterol profile of an ERG25 disruptant was consistent with the erg25 allele obtained by mutagenesis.
Bard, M; Bruner, D A; Pierson, C A; Lees, N D; Biermann, B; Frye, L; Koegel, C; Barbuch, R
How sterol tilt regulates properties and organization of lipid membranes and membrane insertions
Serving as a crucial component of mammalian cells, cholesterol critically regulates the functions of biomembranes. This review focuses on a specific property of cholesterol and other sterols: the tilt modulus ? that quantifies the energetic cost of tilting sterol molecules inside the lipid membrane. We show how ? is involved in determining properties of cholesterol-containing membranes, and detail a novel approach to quantify its value from atomistic molecular dynamics (MD) simulations. Specifically, we link ? with other structural, thermodynamic, and mechanical properties of cholesterol-containing lipid membranes, and delineate how this useful parameter can be obtained from the sterol tilt probability distributions derived from relatively small-scale unbiased MD simulations. We demonstrate how the tilt modulus quantitatively describes the aligning field that sterol molecules create inside the phospholipid bilayers, and we relate ? to the bending rigidity of the lipid bilayer through effective tilt and splay energy contributions to the elastic deformations. Moreover, we show how ? can conveniently characterize the "condensing effect" of cholesterol on phospholipids. Finally, we demonstrate the importance of this cholesterol aligning field to the proper folding and interactions of membrane peptides. Given the relative ease of obtaining the tilt modulus from atomistic simulations, we propose that ? can be routinely used to characterize the mechanical properties of sterol/lipid bilayers, and can also serve as a required fitting parameter in multi-scaled simulations of lipid membrane models to relate the different levels of coarse-grained details.
Khelashvili, George; Harries, Daniel
Phosphatidyl alcohols: Effect of head group size on domain forming properties and interactions with sterols
In this study, we have examined the membrane properties and sterol interactions of phosphatidyl alcohols varying in the size of the alcohol head group coupled to the sn-3-linked phosphate. Phosphatidyl alcohols of interest were dipalmitoyl derivatives with methanol (DPPMe), ethanol (DPPEt), propanol (DPPPr), or butanol (DPPBu) head groups. The Phosphatidyl alcohols are biologically relevant, because they can be formed in
Shishir Jaikishan; Anders Björkbom; J. Peter Slotte
Visualization of sterol-rich membrane domains with fluorescently-labeled theonellamides.
Cholesterol plays important roles in biological membranes. The cellular location where cholesterol molecules work is prerequisite information for understanding their dynamic action. Bioimaging probes for cholesterol molecules would be the most powerful means for unraveling the complex nature of lipid membranes. However, only a limited number of chemical or protein probes have been developed so far for cytological analysis. Here we show that fluorescently-labeled derivatives of theonellamides act as new sterol probes in mammalian cultured cells. The fluorescent probes recognized cholesterol molecules and bound to liposomes in a cholesterol-concentration dependent manner. The probes showed patchy distribution in the plasma membrane, while they stained specific organelle in the cytoplasm. These data suggest that fTNMs will be valuable sterol probes for studies on the role of sterols in the biological membrane under a variety of experimental conditions. PMID:24386262
Nishimura, Shinichi; Ishii, Kumiko; Iwamoto, Kunihiko; Arita, Yuko; Matsunaga, Shigeki; Ohno-Iwashita, Yoshiko; Sato, Satoshi B; Kakeya, Hideaki; Kobayashi, Toshihide; Yoshida, Minoru
An update on plant derived anti-androgens.
Anti-androgens are an assorted group of drugs and compounds that reduce the levels or activity of androgen hormones within the human body. Disease states in which this is relevant include polycystic ovarian syndrome, hirsutism, acne, benign prostatic hyperplasia, and endocrine related cancers such as carcinoma of the prostate. We provide an overview and discussion of the use of anti-androgen medications in clinical practice and explore the increasing recognition of the benefits of plant-derived anti-androgens, for example, spearmint tea in the management of PCOS, for which some evidence about efficacy is beginning to emerge. Other agents covered include red reishi, which has been shown to reduce levels 5-alpha reductase, the enzyme that facilitates conversion of testosterone to dihydrotestosterone (DHT); licorice, which has phytoestrogen effects and reduces testosterone levels; Chinese peony, which promotes the aromatization of testosterone into estrogen; green tea, which contains epigallocatechins and also inhibits 5-alpha reductase, thereby reducing the conversion of normal testosterone into the more potent DHT; black cohosh, which has been shown to kill both androgenresponsive and non-responsive human prostate cancer cells; chaste tree, which has a reduces prolactin from the anterior pituitary; and saw palmetto extract, which is used as an anti-androgen although it shown no difference in comparison to placebo in clinical trials. PMID:23843810
Grant, Paul; Ramasamy, Shamin
Sterol composition of shellfish species commonly consumed in the United States
Background Shellfish can be a component of a healthy diet due to a low fat and high protein content, but the cholesterol content of some species is often cited as a reason to limit their consumption. Data on levels of non-cholesterol sterols in commonly consumed species are lacking. Objective Shellfish were sampled and analyzed to update sterol data in the United States Department of Agriculture (USDA) National Nutrient Database for Standard Reference. Design Using a nationwide sampling plan, raw shrimp and sea scallops, canned clams, and steamed oysters, blue crab, and lobster were sampled from 12 statistically selected supermarkets across the United States in 2007–08. For each species, four composites were analyzed, each comprised of samples from three locations; shrimp and scallops from six single locations were also analyzed separately. Using validated analytical methodology, 14 sterols were determined in total lipid extracts after saponification and derivatization to trimethylsilyethers, using gas chromatography for quantitation and mass spectrometry for confirmation of components. Results Crab, lobster, and shrimp contained significant cholesterol (96.2–27 mg/100 g); scallops and clams had the lowest concentrations (23.4–30.1 mg/100 g). Variability in cholesterol among single-location samples of shrimp was low. The major sterols in the mollusks were brassicasterol (12.6–45.6 mg/100 g) and 24-methylenecholesterol (16.7–41.9 mg/100 g), with the highest concentrations in oysters. Total non-cholesterol sterols were 46.5–75.6 mg/100 g in five single-location scallops samples, but 107 mg/100 g in the sixth, with cholesterol also higher in that sample. Other prominent non-cholesterol sterols in mollusks were 22-dehydrocholesterol, isofucosterol, clionasterol, campesterol, and 24-norcholesta-5,22-diene-3?-ol (4–21 mg/100 g). Conclusions The presence of a wide range of sterols, including isomeric forms, in shellfish makes the analysis and quantitation of sterols in marine species more complex than in animal and plant tissues. The detailed sterol composition reported herein provides data that may be useful in research on the impact of shellfish consumption on dietary risk factors.
Phillips, Katherine M.; Ruggio, David M.; Exler, Jacob; Patterson, Kristine Y.
Universal Behavior of Membranes with Sterols
Lanosterol is the biosynthetic precursor of cholesterol and ergosterol, sterols that predominate in the membranes of mammals and lower eukaryotes, respectively. These three sterols are structurally quite similar, yet their relative effects on membranes have been shown to differ. Here we study the effects of cholesterol, lanosterol, and ergosterol on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipid bilayers at room temperature. Micropipette aspiration is used to determine membrane material properties (area compressibility modulus), and information about lipid chain order (first moments) is obtained from deuterium nuclear magnetic resonance. We compare these results, along with data for membrane-bending rigidity, to explore the relationship between membrane hydrophobic thickness and elastic properties. Together, such diverse approaches demonstrate that membrane properties are affected to different degrees by these structurally distinct sterols, yet nonetheless exhibit universal behavior.
Henriksen, J.; Rowat, A. C.; Brief, E.; Hsueh, Y. W.; Thewalt, J. L.; Zuckermann, M. J.; Ipsen, J. H.
Fluorescent sterols as tools in membrane biophysics and cell biology
Cholesterol is an important constituent of cellular membranes playing a fundamental role in many biological processes. This sterol affects membrane permeability, lateral lipid organization, signal transduction and membrane trafficking. Intracellular sterol transport modes and pathways as well as the regulation of sterol metabolism and disposition in various tissues are areas of intense research. Progress is intimately linked to development and
Daniel Wüstner
The fungal elicitor cryptogein is a sterol carrier protein
Cryptogein is a protein secreted by the phytopathogenic pseudo-fungus, Phytophthora cryptogea. It is a basic 10 kDa hydrophilic protein having a hydrophobic pocket and three disulfide bridges. These common features with sterol carrier proteins led us to investigate its possible sterol transfer activity using the fluorescent sterol, dehydroergosterol. The results show that cryptogein has one binding site with strong affinity
Vladimir Mikes; Marie-Louise Milat; Michel Ponchet; Pierre Ricci; Jean-Pierre Blein
Antibiofilm effect of plant derived antimicrobials on Listeria monocytogenes.
The present study investigated the efficacy of sub-inhibitory concentrations (SICs, concentrations not inhibiting bacterial growth) and bactericidal concentrations (MBCs) of four, generally recognized as safe (GRAS), plant-derived antimicrobials (PDAs) in inhibiting Listeria monocytogenes (LM) biofilm formation and inactivating mature LM biofilms, at 37, 25 and 4 °C on polystyrene plates and stainless-steel coupons. In addition, the effect of SICs of PDAs on the expression of LM genes critical for biofilm synthesis was determined by real-time quantitative PCR. The PDAs and their SICs used for inhibition of biofilm were trans-cinnamaldehyde (TC 0.50, 0.75 mM), carvacrol (CR 0.50, 0.65 mM), thymol (TY 0.33, 0.50 mM), and eugenol (EG 1.8, 2.5 mM), whereas the PDA concentrations used for inactivating mature biofilms were 5.0 and 10.0 mM (TC, CR), 3.3 and 5.0 mM (TY), 18.5 and 25.0 mM (EG). All PDAs inhibited biofilm synthesis and inactivated fully formed LM biofilms on both matrices at three temperatures tested (P < 0.05). Real-time quantitative PCR data revealed that all PDAs down-regulated critical LM biofilm-associated genes (P < 0.05). Results suggest that TC, CR, TY, and EG could potentially be used to control LM biofilms in food processing environments, although further studies under commercial settings are necessary. PMID:23764223
Upadhyay, Abhinav; Upadhyaya, Indu; Kollanoor-Johny, Anup; Venkitanarayanan, Kumar
Plasma membrane lipid-protein interactions affect signaling processes in sterol-biosynthesis mutants in Arabidopsis thaliana
The plasma membrane is an important organelle providing structure, signaling and transport as major biological functions. Being composed of lipids and proteins with different physicochemical properties, the biological functions of membranes depend on specific protein–protein and protein–lipid interactions. Interactions of proteins with their specific sterol and lipid environment were shown to be important factors for protein recruitment into sub-compartmental structures of the plasma membrane. System-wide implications of altered endogenous sterol levels for membrane functions in living cells were not studied in higher plant cells. In particular, little is known how alterations in membrane sterol composition affect protein and lipid organization and interaction within membranes. Here, we conducted a comparative analysis of the plasma membrane protein and lipid composition in Arabidopsis sterol-biosynthesis mutants smt1 and ugt80A2;B1. smt1 shows general alterations in sterol composition while ugt80A2;B1 is significantly impaired in sterol glycosylation. By systematically analyzing different cellular fractions and combining proteomic with lipidomic data we were able to reveal contrasting alterations in lipid–protein interactions in both mutants, with resulting differential changes in plasma membrane signaling status.
Zauber, Henrik; Burgos, Asdrubal; Garapati, Prashanth; Schulze, Waltraud X.
Changes in membrane lipid composition in azuki bean epicotyls under hypergravity conditions: Possible role of membrane sterols in gravity resistance
NASA Astrophysics Data System (ADS)
Seedlings of azuki bean ( Vigna angularis Ohwi et Ohashi) were cultivated under hypergravity conditions, and changes in membrane lipid composition in their epicotyls were analyzed. Under hypergravity conditions at 300 g, the levels of total sterols, phospholipids, and fatty acids per fresh weight were kept higher, as compared with 1 g controls. In particular, sterol levels were prominently increased by hypergravity. On the other hand, hypergravity did not clearly influence the levels of each phospholipid and glycolipid class, or their fatty acid compositions. Thus, the effect of hypergravity on membrane lipid metabolism was specific for sterol biosynthesis. In various regions of azuki epicotyls, high growth rate was associated with high sterol levels. Hypergravity suppressed elongation growth and stimulated lateral expansion of azuki epicotyls. In the presence of lovastatin, an inhibitor of sterol biosynthesis, at 30 ?M, such changes in growth parameters occurred even under 1 g conditions, suggesting that lovastatin made epicotyls hypersensitive to the gravitational force. These results support the hypothesis that membrane sterols are involved in maintenance of normal growth capacity of plant organs against gravity.
Koizumi, T.; Sakaki, T.; Usui, S.; Soga, K.; Wakabayashi, K.; Hoson, T.
The Evolution of Sterol Biosynthesis in Bacteria: In Situ Fluorescence Localization of Sterols in the Nucleoid Bacterium Gemmata obscuriglobus
The biosynthesis of sterols is generally regarded as a eukaryotic process. The first enzymatic step in the production of sterols requires molecular oxygen. Therefore, both the origin of eukaryotes and the evolution of sterol biosynthesis were thought to postdate the rise of oxygen in earth's atmosphere, until Brocks et al. discovered steranes in rocks aged 2.7 Ga (1). Many prokaryotes
M. Budin; T. L. Jorgenson; A. Pearson
Lectin cDNA and transgenic plants derived therefrom
Transgenic plants containing cDNA encoding Gramineae lectin are described. The plants preferably contain cDNA coding for barley lectin and store the lectin in the leaves. The transgenic plants, particularly the leaves exhibit insecticidal and fungicidal properties. GOVERNMENT RIGHTS This application was funded under Department of Energy Contract DE-AC02-76ER01338. The U.S. Government has certain rights under this application and any patent issuing thereon. .
Raikhel, N.V.
Lectin cDNA and transgenic plants derived therefrom
Transgenic plants containing cDNA encoding Gramineae lectin are described. The plants preferably contain cDNA coding for barley lectin and store the lectin in the leaves. The transgenic plants, particularly the leaves exhibit insecticidal and fungicidal properties. GOVERNMENT RIGHTS This application was funded under Department of Energy Contract DE-AC02-76ER01338. The U.S. Government has certain rights under this application and any patent issuing thereon.
Raikhel, Natasha V. (Okemos, MI)
Plant-Derived Anticancer Agents Used in Western and Oriental Medicine
\\u000a Cancer chemotherapeutic agents derived from higher plants are used in Western medicine. Secondary metabolites from plants\\u000a are used in oriental medicine are utilized in anticancer therapy. Immunomodulatory small organic molecules from plant species\\u000a are employed in Chinese traditional medicine are renewed.
Ah-Reum Han; Ye Deng; Yulin Ren; Li Pan; A. Douglas Kinghorn
Sterol transporters: targets of natural sterols and new lipid lowering drugs
Recent insights in the role of ATP-binding cassette (ABC) transporters ABCG5 and ABCG8, the discovery of ezetimibe, the first approved direct cholesterol absorption inhibitor, as well as the identification of Niemann-Pick C1 Like 1 (NPC1L1) protein as sterol transporter in the gut, focused attention on sterol transport processes in the small intestine and the liver. The identification of defective structures
Thomas Sudhop; Dieter Lütjohann; Klaus von Bergmann
A new triazole, voriconazole (UK-109,496), blocks sterol biosynthesis in Candida albicans and Candida krusei.
Voriconazole (UK-109,496) is a novel triazole derivative with potent broad-spectrum activity against various fungi, including some that are inherently resistant to fluconazole, such as Candida krusei. In this study we compared the effect of subinhibitory concentrations of voriconazole and fluconazole on sterol biosynthesis of fluconazole-resistant and -susceptible Candida albicans strains, as well as C. krusei, in an effort to delineate the precise mode of action of voriconazole. Voriconazole MICs ranged from 0.003 to 4 microg/ml, while fluconazole MICs ranged from 0.25 to >64 microg/ml. To investigate the effects of voriconazole and fluconazole on candidal sterols, yeast cells were grown in the absence and presence of antifungals. In untreated C. albicans controls, ergosterol was the major sterol (accounting for 53.6% +/- 2.2% to 71.7% +/- 7.8% of the total) in C. albicans and C. krusei strains. There was no significant difference between the sterol compositions of the fluconazole-susceptible and -resistant C. albicans isolates. Voriconazole treatment led to a decrease in the total sterol content of both C. albicans strains tested. In contrast, exposure to fluconazole did not result in a significant reduction in the total sterol content of the three candidal strains tested (P > 0.5). Gas-liquid chromatographic analysis revealed profound changes in the sterol profiles of both C. albicans strains and of C. krusei in response to voriconazole. This antifungal agent exerted a similar effect on the sterol compositions of both fluconazole-susceptible and -resistant C. albicans strains. Interestingly, a complete inhibition of ergosterol synthesis and accumulation of its biosynthetic precursors were observed in both strains treated with voriconazole. In contrast, fluconazole partially inhibited ergosterol synthesis. Analysis of sterols obtained from a fluconazole-resistant C. albicans strain grown in the presence of different concentrations of voriconazole showed that this agent inhibits ergosterol synthesis in a dose-dependent manner. In C. krusei, voriconazole significantly inhibited ergosterol synthesis (over 75% inhibition). C. krusei cells treated with voriconazole accumulated the following biosynthetic intermediates: squalene, 4,14-dimethylzymosterol, and 24-methylenedihydrolanosterol. Accumulation of these methylated sterols is consistent with the premise that this agent functions by inhibiting fungal P-450-dependent 14alpha-demethylase. As expected, treating C. krusei with fluconazole minimally inhibited ergosterol synthesis. Importantly, our data indicate that voriconazole is more effective than fluconazole in blocking candidal sterol biosynthesis, consistent with the different antifungal potencies of these compounds.
Sanati, H; Belanger, P; Fratti, R; Ghannoum, M
Immunization against Rabies with Plant-Derived Antigen
We previously demonstrated that recombinant plant virus particles containing a chimeric peptide representing two rabies virus epitopes stimulate virus neutralizing antibody synthesis in immunized mice. We show here that mice immunized intraperitoneally or orally (by gastric intubation or by feeding on virus-infected spinach leaves) with engineered plant virus particles containing rabies antigen mount a local and systemic immune response. After
Anna Modelska; Bernard Dietzschold; N. Sleysh; Zhen Fang Fu; Klaudia Steplewski; D. Craig Hooper; Hilary Koprowski; Vidadi Yusibov
Structural genomics of enzymes involved in sterol/isoprenoid biosynthesis
X-ray structures of two enzymes in the sterol/isoprenoid biosynthesis pathway have been determined in a structural genomics pilot study. Mevalonate-5-diphosphate decarboxylase (MDD) is a single-domain ?/? protein that catalyzes the last of three sequential ATP-dependent reactions which convert mevalonate to isopentenyl diphosphate. Isopentenyl disphosphate isomerase (IDI) is an ?/? metalloenzyme that catalyzes interconversion of isopentenyl diphosphate and dimethylallyl diphosphate, which condense in the next step toward synthesis of sterols and a host of natural products. Homology modeling of related proteins and comparisons of the MDD and IDI structures with two other experimentally determined structures have shown that MDD is a member of the GHMP superfamily of small-molecule kinases and IDI is similar to the nudix hydrolases, which act on nucleotide diphosphatecontaining substrates. Structural models were produced for 379 proteins, encompassing a substantial fraction of both protein superfamilies. All three enzymes responsible for synthesis of isopentenyl diphosphate from mevalonate (mevalonate kinase, phosphomevalonate kinase, and MDD) share the same fold, catalyze phosphorylation of chemically similar substrates (MDD decarboxylation involves phosphorylation of mevalonate diphosphate), and seem to have evolved from a common ancestor. These structures and the structural models derived from them provide a framework for interpreting biochemical function and evolutionary relationships.
Bonanno, Jeffrey B.; Edo, Carme; Eswar, Narayanan; Pieper, Ursula; Romanowski, Michael J.; Ilyin, Valentin; Gerchman, Sue Ellen; Kycia, Helen; Studier, F. William; Sali, Andrej; Burley, Stephen K.
Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk
This review integrates historical biochemical and modern genetic findings that underpin our understanding of the low-density lipoprotein (LDL) dyslipidemias that bear on human disease. These range from life-threatening conditions of infancy through severe coronary heart disease of young adulthood, to indolent disorders of middle- and old-age. We particularly focus on the biological aspects of those gene mutations and variants that impact on sterol absorption and hepatobiliary excretion via specific membrane transporter systems (NPC1L1, ABCG5/8); the incorporation of dietary sterols (MTP) and of de novo synthesized lipids (HMGCR, TRIB1) into apoB-containing lipoproteins (APOB) and their release into the circulation (ANGPTL3, SARA2, SORT1); and receptor-mediated uptake of LDL and of intestinal and hepatic-derived lipoprotein remnants (LDLR, APOB, APOE, LDLRAP1, PCSK9, IDOL). The insights gained from integrating the wealth of genetic data with biological processes have important implications for the classification of clinical and presymptomatic diagnoses of traditional LDL dyslipidemias, sitosterolemia, and newly emerging phenotypes, as well as their management through both nutritional and pharmaceutical means.
Calandra, Sebastiano; Tarugi, Patrizia; Speedy, Helen E.; Dean, Andrew F.; Bertolini, Stefano; Shoulders, Carol C.
Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk.
This review integrates historical biochemical and modern genetic findings that underpin our understanding of the low-density lipoprotein (LDL) dyslipidemias that bear on human disease. These range from life-threatening conditions of infancy through severe coronary heart disease of young adulthood, to indolent disorders of middle- and old-age. We particularly focus on the biological aspects of those gene mutations and variants that impact on sterol absorption and hepatobiliary excretion via specific membrane transporter systems (NPC1L1, ABCG5/8); the incorporation of dietary sterols (MTP) and of de novo synthesized lipids (HMGCR, TRIB1) into apoB-containing lipoproteins (APOB) and their release into the circulation (ANGPTL3, SARA2, SORT1); and receptor-mediated uptake of LDL and of intestinal and hepatic-derived lipoprotein remnants (LDLR, APOB, APOE, LDLRAP1, PCSK9, IDOL). The insights gained from integrating the wealth of genetic data with biological processes have important implications for the classification of clinical and presymptomatic diagnoses of traditional LDL dyslipidemias, sitosterolemia, and newly emerging phenotypes, as well as their management through both nutritional and pharmaceutical means. PMID:21862702
Calandra, Sebastiano; Tarugi, Patrizia; Speedy, Helen E; Dean, Andrew F; Bertolini, Stefano; Shoulders, Carol C
Plant-derived Compounds for the Treatment of Retroviral Diseases
NIH Researchers have identified Englerin A and its derivatives as potent and specific activators of viral replication in infected T cells (with a decrease of about 70% of activated T-reg population following ex-vivo PBMCs treatment).
Physiological and proteomic approaches to evaluate the role of sterol binding in elicitin-induced resistance
Cryptogein is a proteinaceous elicitor secreted by Phytophthora cryptogea that can induce resistance to P. parasitica in tobacco plants. On the basis of previous computer modelling experiments, by site-directed mutagenesis a series of cryptogein variants was prepared with altered abilities to bind sterols, phospholipids or both. The sterol binding and phospholipid transfer activities corresponded well with the previously reported structural data. Induction of the synthesis of reactive oxygen species (ROS) in tobacco cells in suspension and proteomic analysis of intercellular fluid changes in tobacco leaves triggered by these mutant proteins were not proportional to their ability to bind or transfer sterols and phospholipids. However, changes in the intercellular proteome corresponded to transcription levels of defence genes and resistance to P. parasitica and structure-prediction of mutants did not reveal any significant changes in protein structure. These results suggest, contrary to previous proposals, that the sterol-binding ability of cryptogein and its mutants, and the associated conformational change in the ?-loop, might not be principal factors in either ROS production or resistance induction. Nevertheless, the results support the importance of the ?-loop for the interaction of the protein with the high affinity binding site on the plasma membrane.
Dokladal, Ladislav; Oboril, Michal; Stejskal, Karel; Zdrahal, Zbynek; Ptackova, Nikola; Chaloupkova, Radka; Damborsky, Jiri; Kasparovsky, Tomas; Jeandroz, Sylvain; Zd'arska, Marketa; Lochman, Jan
Validation of deuterium incorporation against sterol balance for measurement of human cholesterol biosynthesis.
To examine the validity of the deuterium (D) incorporation technique for measurement of human cholesterol synthesis rates, D uptake from D2O into cholesterol was compared to sterol balance in 13 subjects each under three controlled diet settings. Subjects (age 62 +/- 3.6 yr, body weight 74 +/- 4.0 kg, BMI 27 +/- 1.4) consumed weight maintenance diets enriched in either corn oil, beef tallow, or stick corn oil margarine over a 5-week period. During the final week of the study period, subjects were given 1.2 g/D2O per kg body water. D enrichment was measured in plasma water and total cholesterol over 24 h. Also, during the final week, dietary intake and fecal elimination rates of cholesterol were assessed over one 6-day period to calculate sterol balance. There was no significant difference (t = 0.858, P = 0.397) between D incorporation into cholesterol (1,183 +/- 92 mg/day) and sterol balance (1,316 +/- 125 mg/day). Among diets, net cholesterol biosynthesis measured by D incorporation agreed (r = 0.745, P = 0.0001) with values derived from sterol balance. The degree of association between methods was not influenced by the wide range of fatty acid composition of the diet fat. These data demonstrate the utility of the simple, non-restrictive deuterium incorporation method as a reliable means of determining cholesterol biosynthesis in free-living humans. PMID:9610780
Jones, P J; Ausman, L M; Croll, D H; Feng, J Y; Schaefer, E A; Lichtenstein, A H
Quinones derived from plant secondary metabolites as anti-cancer agents.
Quinones are plant-derived secondary metabolites that present some anti-proliferation and anti-metastasis effects in various cancer types both in vitro and in vivo. This review focuses on the anti-cancer prospects of plant-derived quinones, namely, aloe-emodin, juglone, ?-lapachol, plumbagin, shikonin, and thymoquinone. We intend to summarize their anti-cancer effects and investigate the mechanism of actions to promote the research and development of anti-cancer agents from quinones. PMID:22931417
Lu, Jin-Jian; Bao, Jiao-Lin; Wu, Guo-Sheng; Xu, Wen-Shan; Huang, Ming-Qing; Chen, Xiu-Ping; Wang, Yi-Tao
Triterpene alcohols and sterols of vegetable oils
Triterpene alcohols and sterols were separated by thin-layer chromatography and gas-liquid chromatography from the unsaponifiable\\u000a fractions of the following 18 vegetable oils: linseed, peanut, olive, rice bran, palm kernel, corn, sesame, oiticica, palm,\\u000a coconut, rapeseed, grape seed, sunflower, poppy seed, castor, tea seed, cocoa butter and soybean. Two triterpene alcohols,\\u000a cycloartenol and 24-methylene cycloartanol, were found in all of the
E. Fedeli; A. Lanzani; P. Capella; G. Jacini
Osteolytic Sterol in Human Breast Cancer
Eleven of twelve human breast cancers contained a lipid which increased urinary 45Ca and 40Ca excretion of 45Ca-labeled, parathyroidectomized rats receiving a low Ca diet. The lipid has mobility on thin-layer chromatography and gas-liquid chromatography close to, but not identical with, that of 7-dehydrocholesterol. Authentic 7-dehydrocholesterol has osteolytic activity similar to that of the extracted sterol. Fluorescence and Lieberman-Burchard reactions
Gilbert S. Gordan; Theodore J. Cantino; Linda Erhardt; James Hansen; Warren Lubich
Immunization against Rabies with Plant-Derived Antigen
NASA Astrophysics Data System (ADS)
We previously demonstrated that recombinant plant virus particles containing a chimeric peptide representing two rabies virus epitopes stimulate virus neutralizing antibody synthesis in immunized mice. We show here that mice immunized intraperitoneally or orally (by gastric intubation or by feeding on virus-infected spinach leaves) with engineered plant virus particles containing rabies antigen mount a local and systemic immune response. After the third dose of antigen, given intraperitoneally, 40% of the mice were protected against challenge infection with a lethal dose of rabies virus. Oral administration of the antigen stimulated serum IgG and IgA synthesis and ameliorated the clinical signs caused by intranasal infection with an attenuated rabies virus strain.
Modelska, Anna; Dietzschold, Bernard; Sleysh, N.; Fu, Zhen Fang; Steplewski, Klaudia; Hooper, D. Craig; Koprowski, Hilary; Yusibov, Vidadi
Plant derivatives in the treatment of alcohol dependency
The present review summarizes the findings of the effects of extracts of purified compounds from several plants on alcohol intake in alcohol-preferring rats. These include St. John's wort (Hypericum perforatum, HPE), kudzu (Pueraria lobata) and ibogaine (Tabernanthe iboga). Alcohol-preferring (P), Marchigian Sardinian (msP), high-alcohol-drinking (HAD), Fawn-Hooded (FH) rats were allowed to drink alcohol or water voluntarily to establish baseline levels.
Amir H Rezvani; David H Overstreet; Marina Perfumi; Maurizio Massi
The biosynthesis and metabolism of the aspartate derived amino acids in higher plants
The essential amino acids lysine, threonine, methionine and isoleucine are synthesised in higher plants via a common pathway starting with aspartate. The regulation of the pathway is discussed in detail, and the properties of the key enzymes described. Recent data obtained from studies of regulation at the gene level and information derived from mutant and transgenic plants are also discussed.
Ricardo A. Azevedo; Paulo Arruda; William L. Turner; Peter J. Lea
Sterol Structure Determines Miscibility versus Melting Transitions in Lipid Vesicles
Lipid bilayer membranes composed of DOPC, DPPC, and a series of sterols demix into coexisting liquid phases below a miscibility transition temperature. We use fluorescence microscopy to directly observe phase transitions in vesicles of 1:1:1 DOPC\\/DPPC\\/sterol within giant unilamellar vesicles. We show that vesicles containing the "promoter" sterols cholesterol, ergosterol, 25-hydroxycholesterol, epicholesterol, or dihydrocholesterol demix into coexisting liquid phases as
Mary Elizabeth Beattie; Sarah L. Veatch; Benjamin L. Stottrup; Sarah L. Keller
Distribution of sterols in the fungi. I - Fungal spores
NASA Technical Reports Server (NTRS)
Mass spectrometry was used to examine freely extractable sterols from spores of several species of fungi. Ergosterol was the most common sterol produced by any individual species, but it was completely absent from two species belonging to apparently distantly related groups of fungi: the aquatic Phycomycetes and the rust fungi. This fact could have taxonomic or phylogenetic implications. The use of glass capillary columns in the resolution of the sterols is shown to eliminate some of the difficulty inherent in this process.
Weete, J. D.; Laseter, J. L.
Development of Fly Ash Derived Sorbents to Capture CO2 from Flue Gas of Power Plants
This research program focused on the development of fly ash derived sorbents to capture CO from power plant flue gas emissions. The fly ash derived sorbents developed represent an affordable alternative to existing methods using specialized activated carbons and molecular sieves, that tend to be very expensive and hinder the viability of the CO sorption process due to economic constraints.
M. Mercedes Maroto-Valer; John M. Andresen; Yinzhi Zhang; Zhe Lu
Tracing origins of sewage and organic matter using dissolved sterols in Masan and Haengam Bay, Korea
Masan and Haengam Bays in Korea are highly polluted and semi-enclosed. Domestic and industrial effluents are directly or indirectly\\u000a discharged into the bays through sewage treatment plants (STP) and creeks. In this study, 15 dissolved sterol compounds were\\u000a determined in order to understand their sources and relative contribution. Freshwater samples were taken from 13 creeks and\\u000a at two STP sites
Hyo Jin Lee; Sang Hee Hong; Moonkoo Kim; Sung Yong Ha; Soon Mo An; Won Joon Shim
Efficient chimeric plant promoters derived from plant infecting viral promoter sequences.
In the present study, we developed a set of three chimeric/hybrid promoters namely FSgt-PFlt, PFlt-UAS-2X and MSgt-PFlt incorporating different important domains of Figwort Mosaic Virus sub-genomic transcript promoter (FSgt, -270 to -60), Mirabilis Mosaic Virus sub-genomic transcript promoter (MSgt, -306 to -125) and Peanut Chlorotic Streak Caulimovirus full-length transcript promoter (PFlt-, -353 to +24 and PFlt-UAS, -353 to -49). We demonstrated that these chimeric/hybrid promoters can drive the expression of reporter genes in different plant species including tobacco, Arabidopsis, petunia, tomato and spinach. FSgt-PFlt, PFlt-UAS-2X and MSgt-PFlt promoters showed 4.2, 1.5 and 1.2 times stronger GUS activities compared to the activity of the CaMV35S promoter, respectively, in tobacco protoplasts. Protoplast-derived recombinant promoter driven GFP showed enhanced accumulation compared to that obtained under the CaMV35S promoter. FSgt-PFlt, PFlt-UAS-2X and MSgt-PFlt promoters showed 3.0, 1.3 and 1.0 times stronger activities than the activity of the CaMV35S˛ (a modified version of the CaMV35S promoter with double enhancer domain) promoter, respectively, in tobacco (Nicotiana tabacum, var. Samsun NN). Alongside, we observed a fair correlation between recombinant promoter-driven GUS accumulation with the corresponding uidA-mRNA level in transgenic tobacco. Histochemical (X-gluc) staining of whole transgenic seedlings and fluorescence images of ImaGene Green™ treated floral parts expressing the GUS under the control of recombinant promoters also support above findings. Furthermore, we confirmed that these chimeric promoters are inducible in the presence of 150 ?M salicylic acid (SA) and abscisic acid (ABA). Taken altogether, we propose that SA/ABA inducible chimeric/recombinant promoters could be used for strong expression of gene(s) of interest in crop plants. PMID:24178585
Acharya, Sefali; Ranjan, Rajiv; Pattanaik, Sitakanta; Maiti, Indu B; Dey, Nrisingha
Ribulose Bisphosphate Carboxylase Activity in Anther-Derived Plants of Saintpaulia ionantha Wendl. Shag 1
Plants obtained from anther culture of the African violet, Saintpaulia ionantha Wendl. `Shag' and vegetatively cloned copies of the parent anther donor plant were examined for their ploidy and ribulose-1,5-biphosphate carboxylase (RuBPcase) activity. The cloned parent plants were all diploid and did not vary much in their nuclear DNA, chlorophyll, and RuBPcase activity. Some of the anther-derived plants were similar to the parent plants while others were not. Different levels of ploidy were observed among the androgenetic plants. RuBPcase activities higher than that of the parent plants were found in some anther-derived plants. However, there was no direct correlation between ploidy and RuBPcase activity. Expression of nuclear genes from a single parent in the anther-derived plants and it's diploidization or plastid changes during early stages of microsporogenesis or androgenesis are suggested as possible reasons for the variations observed among them. This could be a useful technique to obtain physiological variants which could be agronomically desirable. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4
Bhaskaran, Shyamala; Smith, Roberta H.; Finer, John J.
Insulin-induced gene protein (INSIG)-dependent sterol regulation of Hmg2 endoplasmic reticulum-associated degradation (ERAD) in yeast.
Insulin-induced gene proteins (INSIGs) function in control of cellular cholesterol. Mammalian INSIGs exert control by directly interacting with proteins containing sterol-sensing domains (SSDs) when sterol levels are elevated. Mammalian 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (HMGR) undergoes sterol-dependent, endoplasmic-reticulum (ER)-associated degradation (ERAD) that is mediated by INSIG interaction with the HMGR SSD. The yeast HMGR isozyme Hmg2 also undergoes feedback-regulated ERAD in response to the early pathway-derived isoprene gernanylgeranyl pyrophosphate (GGPP). Hmg2 has an SSD, and its degradation is controlled by the INSIG homologue Nsg1. However, yeast Nsg1 promotes Hmg2 stabilization by inhibiting GGPP-stimulated ERAD. We have proposed that the seemingly disparate INSIG functions can be unified by viewing INSIGs as sterol-dependent chaperones of SSD clients. Accordingly, we tested the role of sterols in the Nsg1 regulation of Hmg2. We found that both Nsg1-mediated stabilization of Hmg2 and the Nsg1-Hmg2 interaction required the early sterol lanosterol. Lowering lanosterol in the cell allowed GGPP-stimulated Hmg2 ERAD. Thus, Hmg2-regulated degradation is controlled by a two-signal logic; GGPP promotes degradation, and lanosterol inhibits degradation. These data reveal that the sterol dependence of INSIG-client interaction has been preserved for over 1 billion years. We propose that the INSIGs are a class of sterol-dependent chaperones that bind to SSD clients, thus harnessing ER quality control in the homeostasis of sterols. PMID:23306196
Theesfeld, Chandra L; Hampton, Randolph Y
Synthesis of the fatty sterol bound protein for a new sterol antibody.
For the purpose of applying the particular antibodies as a new diagnostic procedure for atherosclerosis and related diseases, we successfully achieved the synthesis of the fatty sterol with a linker, then linked the target protein to this sterol. Synthesis was started from pregnenolone and achieved by the Grignard reaction with pentenyl magnesium bromide, regioselective photoaddition of thiolacetic acid toward the 25-double bond, esterification of 3-OH with linoleic anhydride, in situ conjunction of the cross-linker (MBS) to the thiol group after selective deprotection from its acetyl ester, and finally by the reaction with protein such as KLH or albumin through this linker. PMID:10714499
Kim, B J; Yamada, S; Funada, T; Kadoma, Y; Morita, H
Apoptosis-induced release of mature sterol regulatory element-binding proteins activates sterol-responsive genes
It is well established that during the execution of the apoptotic cascade, activated caspase 3 releases sterol regulatory element-binding proteins (SREBP) from the membrane of the endoplasmic reticulum in a proteolytic re- action that is distinct from their normal sterol-dependent activation. However, it is not known whether these tran- scription factors are capable of activating sterol-responsive genes under such conditions.
Maureen E. Higgins; Yiannis A. Ioannou
Plant-derived therapeutics for the treatment of metabolic syndrome
Metabolic syndrome is defined as a set of coexisting metabolic disorders that increase an individual's likelihood of developing type 2 diabetes, cardiovascular disease and stroke. Medicinal plants, some of which have been used for thousands of years, serve as an excellent source of bioactive compounds for the treatment of metabolic syndrome because they contain a wide range of phytochemicals with diverse metabolic effects. In order for botanicals to be effectively used against metabolic syndrome, however, botanical preparations must be characterized and standardized through the identification of their active compounds and respective modes of action, followed by validation in controlled clinical trials with clearly defined endpoints. This review assesses examples of commonly known and partially characterized botanicals to describe specific considerations for the phytochemical, preclinical and clinical characterization of botanicals associated with metabolic syndrome.
Graf, Brittany L; Raskin, Ilya; Cefalu, William T; Ribnicky, David M
A search for mosquito larvicidal compounds by blocking the sterol carrying protein, AeSCP-2, through computational screening and docking strategies
Background: Sterol is a very vital compound for most of the insects and mosquitoes to complete their life cycle. Unfortunately mosquitoes cannot synthesize the sterol, it depends on mammals for the same. Mosquitoes take the sterol from the plant decays during their larval stage in the form of phytosterol, which is then converted to cholesterol for further growth and reproduction. This conversion occurs with the help of the sterol carrier protein 2(SCP2). Methods: Mosquito populations are controlled by plant-based inhibitors, which inhibit sterol carrier protein (SCPI-Sterol carrier protein inhibitor) activity. In this article, we explain the methods of inhibiting Aedes aegypti SCP2 by insilico methods including natural inhibitor selection and filtrations by virtual screening and interaction studies. Results: In this study protein-ligand interactions were carried out with various phytochemicals, as a result of virtual screening Alpha-mangostin and Panthenol were found to be good analogs, and were allowed to dock with the mosquito cholesterol carrier protein AeSCP-2. Conclusion: Computational selections of SCPIs are highly reliable and novel methods for discovering new and more effective compounds to control mosquitoes.
Kumar, R. Barani; Shanmugapriya, B.; Thiyagesan, K.; Kumar, S. Raj; Xavier, Suresh M.
X-ray Structure of 4,4?-Dihydroxybenzophenone Mimicking Sterol Substrate in the Active Site of Sterol 14?-Demethylase (CYP51)*S??
A universal step in the biosynthesis of membrane sterols and steroid hormones is the oxidative removal of the 14?-methyl group from sterol precursors by sterol 14?-demethylase (CYP51). This enzyme is a primary target in treatment of fungal infections in organisms ranging from humans to plants, and development of more potent and selective CYP51 inhibitors is an important biological objective. Our continuing interest in structural aspects of substrate and inhibitor recognition in CYP51 led us to determine (to a resolution of 1.95Ĺ) the structure of CYP51 from Mycobacterium tuberculosis (CYP51Mt) co-crystallized with 4,4?-dihydroxybenzophenone (DHBP), a small organic molecule previously identified among top type I binding hits in a library screened against CYP51Mt. The newly determined CYP51Mt-DHBP structure is the most complete to date and is an improved template for three-dimensional modeling of CYP51 enzymes from fungal and prokaryotic pathogens. The structure demonstrates the induction of conformational fit of the flexible protein regions and the interactions of conserved Phe-89 essential for both fungal drug resistance and catalytic function, which were obscure in the previously characterized CYP51Mt-estriol complex. DHBP represents a benzophenone scaffold binding in the CYP51 active site via a type I mechanism, suggesting (i) a possible new class of CYP51 inhibitors targeting flexible regions, (ii) an alternative catalytic function for bacterial CYP51 enzymes, and (iii) a potential for hydroxybenzophenones, widely distributed in the environment, to interfere with sterol biosynthesis. Finally, we show the inhibition of M. tuberculosis growth by DHBP in a mouse macrophage model.
Eddine, Ali Nasser; von Kries, Jens P.; Podust, Mikhail V.; Warrier, Thulasi; Kaufmann, Stefan H. E.; Podust, Larissa M.
Vermicompost derived from different feedstocks as a plant growth medium.
This study determined feedstock effects on earthworm populations and the quality of resulting vermicomposts produced from different types of feedstocks using different vermicomposting durations. Feedstock combinations (Kitchen Paper Waste (KPW), Kitchen Yard Waste (KYW), Cattle Manure Yard Waste (CMY)), three durations of vermicomposting (45, 68 or 90 days), and two seed germination methods (with two concentrations of vermicompost) for radish, marigold and upland cress, served as the independent variables. The worms (Eisenia fetida) doubled their weight by day 68 in KPW and CMY vermicomposts and day 90 KPW vermicompost produced the greatest weight of worms. The direct seed germination method (seeding into soil or vermicompost-soil mixtures) indicated that KPW and KYW feedstocks decreased germination compared to the control, even in mature vermicompost. Seed germination was greater in the water extract method; however, most of the vermicompost extracts suppressed germination of the three seed species compared to the water controls. Vermicomposts from all three feedstocks increased leaf area and biomass compared to the control, especially in the 10% vermicompost:soil mix. Thus, seed germination and leaf area or plant biomass for these three species are contrasting vermicompost quality indicators. PMID:20153632
Warman, P R; Anglopez, M J
Displacement of sterols from sterol\\/sphingomyelin domains in fluid bilayer membranes by competing molecules
The formation of sterol and palmitoyl sphingomyelin enriched ordered domains in a fluid bilayer was examined using domain selective fluorescent reporter molecules (cholestatrienol and trans-parinaric acid containing lipids) together with a quencher molecule in the fluid phase. The aim of the study was to explore how stable the ordered domains were and how different, biologically interesting, membrane intercalators could affect
Sonja M. K. Alanko; Katrin K. Halling; Stina Maunula; J. Peter Slotte; Bodil Ramstedt
The Role of Insect-Derived Cues in Eliciting Indirect Plant Defenses in Tobacco, Nicotiana tabacum
In response to insect feeding, plants release complex volatile blends that are important host-location cues for natural enemies of herbivores. These induced volatile responses are mediated by insect-derived cues and differ significantly from responses to mechanical wounding. To improve understanding of the cues that elicit plant volatile responses, we explored the effects of Heliothis virescens saliva on volatile induction in tobacco, Nicotiana tabacum, using an ablation technique that prevents the release of saliva from the labial glands during feeding. Plants damaged by intact caterpillars released 11 volatile compounds. Ablated caterpillars induced these same 11 compounds plus an additional eight. Of the 11 shared compounds, plants damaged by ablated caterpillars released greater quantities of six, most notably volatile nicotine, compared to plants damaged by intact caterpillars. We further investigated the effects of H. virescens oral secretions on volatile induction through the collection and application of caterpillar regurgitant and saliva to mechanically wounded plants. Plants treated with H. virescens regurgitant released significantly more volatile nicotine than plants treated with saliva or those damaged by intact caterpillars. Additionally, application of a mixture of saliva and regurgitant induced less volatile nicotine compared to treatment with regurgitant alone. Our results suggest that saliva has an inhibitory effect on plant volatile responses to H. virescens feeding and that insect-derived cues originating from both regurgitant and saliva may interact to elicit the volatile "signature" of H. virescens.
Delphia, Casey M; Mescher, Mark C; Felton, Gary W
Side effects of the sterol biosynthesis inhibitor fungicide, propiconazole, on a beneficial arbuscular mycorrhizal fungus.
The Sterol Biosynthesis Inhibitor (SBI) fungicide, propiconazole, is extensively used in modern agriculture to control fungal diseases. Unfortunately, little is known about its potential side effects on non-target plant-beneficial soil organisms such as arbuscular mycorrhizal fungi (AMF). The direct impact of increasing propiconazole concentrations (0.02; 0.2 and 2 mg x L(-1)) on the lipid metabolism of the AMF Glomus irregulare in relation with its development, was studied by using axenic cultures. The propiconazole impact on G. irregulare was investigated, firstly, through sterol (the target-metabolism of SBI fungicides), phospholipids (PL) and their associated fatty acids (PLFA) analysis (the main membrane components) and secondly by measuring malondialdehyde (MDA) (a biomarker of lipid peroxidation) formation. Finally, the storage lipid quantity, triacylglycerol (TAG), was quantified. Our results demonstrated that the drastic reduction of G. irregulare development (germination, germ tube elongation, colonization, extraradical hyphae growth and sporulation) could be explained not only by the decreases of the total sterol end-products (24-methylcholesterol and 24-ethylcholesterol) and by 24-methylene dihydrolanosterol (a sterol precursor) accumulation, suggesting an inhibition of a key enzyme in sterol biosynthesis pathway (14alpha-demethylase), but also by the increases in phosphatidylcholine (PC) and PLFA (C16:0; C18:0 and C18:3) quantities as well as by MDA accumulation. Moreover, TAG quantity was found to be reduced in the presence of propiconazole, suggesting their use by G. irregulare in a response to propiconazole toxicity. In conclusion, taken together, the findings of the current study highlighted a relationship between the SBI fungicide toxicity against the beneficial AMF G. irregulare and (1) the disturbance in the sterol metabolism, (2) the membrane alteration (PC decrease, lipid peroxidation) as well as (3) the reduction in storage lipids, TAG. More generally, this work could contribute to investigate the toxicity of agricultural chemicals on AMF and underlined the emergency of using sustainable alternative method to control plant diseases. Furthermore, these data can provide a useful approach in soil ecotoxicology studies and risk assessment. PMID:22702206
Calonne, M; Fontaine, J; Debiane, D; Laruelle, F; Grandmougin, A; Lounes-Hadj Sahraoui, A
Terrestrial Plant-Derived Anticancer Agents and Plant Species Used in Anticancer Research
Cancer is a major cause of death and the number of new cases, as well as the number of individuals living with cancer, is expanding continuously. Due to the enormous propensity of plants that synthesize mixtures of structurally diverse bioactive compounds, the plant kingdom is potentially a very diverse source of chemical constituents with tumor cytotoxic activity. Despite the successful
Spiridon E. Kintzios
Use of plant fatty acyl hydroxylases to produce hydroxylated fatty acids and derivatives in plants
The present invention relates to the identification of nucleic acid sequences and constructs, and methods related thereto, and the use of these sequences and constructs to produce genetically modified plants for the purpose of altering the composition of plant oils, waxes and related compounds.
Somerville, Chris (Portola Valley, CA); van de Loo, Frank (Lexington, KY)
Use of plant fatty acyl hydroxylases to produce hydroxylated fatty acids and derivatives in plants
The present invention relates to the identification of nucleic acid sequences and constructs, and methods related thereto, and the use of these sequences and constructs to produce genetically modified plants for the purpose of altering the composition of plant oils, waxes and related compounds.
Somerville, Chris (Portola Valley, CA); van de Loo, Frank (Lexington, KY)
Use of plant fatty acyl hydroxylases to produce hydroxylated fatty acids and derivatives in plants
The present invention relates to the identification of nucleic acid sequences and constructs, and methods related thereto, and the use of these sequences and constructs to produce genetically modified plants for the purpose of altering the composition of plant oils, waxes and related compounds.
Somerville, Chris (Portola Valley, CA); van de Loo, Frank (Lexington, KY)
A Plant-Derived Remedy for Repair of Infarcted Heart
Background Myocardial infarction (MI) due to coronary artery disease remains one of the leading causes of premature death. Replacement of infarcted heart tissue with regenerating myocardium from endogenous progenitor pools or exogenously introduced stem cells remains a therapeutic ideal. Their impracticality mainly lies in their low efficiency in cardiogenic differentiation (CD). Our recent studies with an acute MI animal model have already demonstrated the therapeutic effect of the MeOH extract of Geum japonicum (EGJ), providing clear evidence of myocardial regeneration. Methods and Findings The present study further isolated the active component contained in EGJ using bioassay-guided isolation and investigated its efficacy in the treatment of infarcted heart in animal MI models. We demonstrated that substantial repair of infarcted heart in animal MI models by EGJ can be mimicked by the isolated candidate compound (cardiogenin) in MI animal models. Clear evidence of newly regenerated endogenous mesenchymal stem cells (MSCs) derived cardiomyocytes was observed throughout the infarct zone, accompanied by significantly improved functional performance of the heart. Transplantation of MSCs pretreated with EGJ or cardiogenin into a MI animal model also resulted in substantial regeneration of functional myocardium, implying that the activated MSCs carry all the necessary blueprints for myocardial regeneration. Signaling pathways specific to cell survival, CD identified in embryonic heart induction and angiogenesis were activated in both cardiogenin-treated MSCs and cardiogenin-induced regenerating myocardium. Conclusions This study has demonstrated the therapeutic effects of cardiogenin in infarcted heart repair, and identified the associated signalling pathways for effective cardiogenic differentiation of MSCs, cell survival and angiogenesis. These findings should enable new treatment strategies for MI to be developed immediately.
Cheng, Lei; Chen, Hao; Yao, Xinsheng; Qi, Guoqing; Liu, Hongwei; Lee, Kwongman; Lee, Kaho; Zhang, Jieting; Chen, Shihui; Lin, Xiaoli; Zhao, Wenchao; Li, Jiankuan; Li, Ming
The sterol composition of marine microalgae has been shown to be a chemotaxonomic property potentially of value in distinguishing members of different algal classes. For example, members of the class Dinophyceae display sterol compositions ranging from as few as two (cholesterol ...
Sterol-Rich Plasma Membrane Domains in Fungi
Concepts regarding the eukaryotic plasma membrane have been evolving in light of growing evidence that it is segregated into distinct lateral domains known as lipid rafts. These sterol- and sphingolipid-rich raft domains are thought to play impor- tant roles in dynamic processes, including protein sorting, cell polarity, and signal transduction. Because of this, it has been very intriguing that sterol-rich
Francisco J. Alvarez; Lois M. Douglas; James B. Konopka
Sterol Requirement for Reproduction of a Free-Living Nematode
The free-living, hermaphroditic nematode Caenorhabditis briggsae has a nutritional requirement for sterols. It will reproduce indefinitely in a liquid medium containing only bacterial cells (Escherichia coli) and salts if various sterols are present. Several other lipid-soluble materials are ineffective in supporting reproduction.
W. F. Hieb; Morton Rothstein
Selective sterol accumulation in ABCG5\\/ABCG8-deficient mice
The ATP binding cassette (ABC) transporters ABCG5 and ABCG8 limit intestinal absorption and promote biliary secretion of neutral sterols. Mutations in either gene cause sitosterolemia, a rare recessive disease in which plasma and tissue levels of several neutral sterols are in- creased to varying degrees. To determine why patients with sitosterolemia preferentially accumulate noncholesterol ste- rols, levels of cholesterol and
Liqing Yu; Klaus von Bergmann; Dieter Lutjohann; Helen H. Hobbs; Jonathan C. Cohen
Removal of resin acids and sterols from pulp mill effluents by activated sludge treatment.
The wastewater treatment plant of an elemental chlorine free bleaching kraft pulp mill located in eastern Finland was sampled in order to study the fate of wood extractives and the toxicity to luminescence bacteria (Vibrio fischeri) in different parts of the plant. Resin acids and sterols were analyzed from water, particles and sludge samples during three different runs. Waters before biotreatment and primary sludge were found to be toxic; but in the activated sludge treatment toxicity was removed. During wastewater treatment, concentrations of wood extractives were reduced over 97%. In activated sludge treatment, over 94% of the resin acids and over 41% of the sterols were degraded or transformed to other compounds. Furthermore, in general, less than 5% of the resin acids and over 31% of the sterols were removed in biosludge to the sludge thickener. Most of the extractives were discharged attached to particles. Although some disturbing factors increased the load of wood extractives during samplings, these factors did not affect the operational efficiency of the secondary treatment system. PMID:12767285
Kostamo, A; Kukkonen, J V K
N-Glycosylation Modification of Plant-Derived Virus-Like Particles: An Application in Vaccines
Plants have been developed as an alternative system to mammalian cells for production of recombinant prophylactic or therapeutic proteins for human and animal use. Effective plant expression systems for recombinant proteins have been established with the optimal combination of gene expression regulatory elements and control of posttranslational processing of recombinant glycoproteins. In plant, virus-like particles (VLPs), viral "empty shells" which maintain the same structural characteristics of virions but are genome-free, are considered extremely promising as vaccine platforms and therapeutic delivery systems. Unlike microbial fermentation, plants are capable of carrying out N-glycosylation as a posttranslational modification of glycoproteins. Recent advances in the glycoengineering in plant allow human-like glycomodification and optimization of desired glycan structures for enhancing safety and functionality of recombinant pharmaceutical glycoproteins. In this review, the current plant-derived VLP approaches are focused, and N-glycosylation and its in planta modifications are discussed.
Jeon, Jae-Heung; Lee, Kyung Jin; Ko, Kisung
Bacterial source tracking from diverse land use catchments by sterol ratios.
Water samples from sites potentially impacted by septic tanks, cattle, sewage treatment plant (STP) and natural forests were collected at regular monthly intervals and within 48 h of rainfall events between October 2004 and June 2006. All samples (n=296) were analysed for faecal coliforms and faecal sterols including coprostanol, epicoprostanol, cholestanol, cholesterol and 24-ethylcoprostanol. Faecal sterol ratios were used to assign human and/or herbivore contamination sources and to estimate their percentage relative contributions in water samples. The catchments had significantly different profiles of designated contamination origins (p<0.05), which were consistent with land use patterns. The STP impacted site had the highest incidence of human contamination assignations and the highest mean levels of coprostanol, whilst the forested site had the highest incidence of uncontaminated samples and the lowest mean concentration of coprostanol. Coprostanol concentrations were not always correlated with faecal coliform counts. PMID:17433407
Shah, Vikaskumar G; Hugh Dunstan, R; Geary, Phillip M; Coombes, Peter; Roberts, Timothy K; Rothkirch, Tony
Analysis of plant-derived miRNAs in animal small RNA datasets
Background Plants contain significant quantities of small RNAs (sRNAs) derived from various sRNA biogenesis pathways. Many of these sRNAs play regulatory roles in plants. Previous analysis revealed that numerous sRNAs in corn, rice and soybean seeds have high sequence similarity to animal genes. However, exogenous RNA is considered to be unstable within the gastrointestinal tract of many animals, thus limiting potential for any adverse effects from consumption of dietary RNA. A recent paper reported that putative plant miRNAs were detected in animal plasma and serum, presumably acquired through ingestion, and may have a functional impact in the consuming organisms. Results To address the question of how common this phenomenon could be, we searched for plant miRNAs sequences in public sRNA datasets from various tissues of mammals, chicken and insects. Our analyses revealed that plant miRNAs were present in the animal sRNA datasets, and significantly miR168 was extremely over-represented. Furthermore, all or nearly all (>96%) miR168 sequences were monocot derived for most datasets, including datasets for two insects reared on dicot plants in their respective experiments. To investigate if plant-derived miRNAs, including miR168, could accumulate and move systemically in insects, we conducted insect feeding studies for three insects including corn rootworm, which has been shown to be responsive to plant-produced long double-stranded RNAs. Conclusions Our analyses suggest that the observed plant miRNAs in animal sRNA datasets can originate in the process of sequencing, and that accumulation of plant miRNAs via dietary exposure is not universal in animals.
New phenyl derivatives from endophytic fungus Aspergillus flavipes AIL8 derived of mangrove plant Acanthus ilicifolius.
Two new aromatic butyrolactones, flavipesins A (1) and B (2), two new natural products (3 and 4), and a known phenyl dioxolanone (5) were isolated from marine-derived endophytic fungus Aspergillus flavipes. The structures of compounds 1-5 were elucidated by 1D- and 2D-NMR and MS analysis, the absolute configurations were assigned by optical rotation and CD data, and the stereochemistry of 1 was determined by X-ray crystallography analysis. 1 demonstrated lower MIC values against Staphylococcus aureus (8.0 ?g/mL) and Bacillus subtillis (0.25 ?g/mL). 1 also showed the unique antibiofilm activity of penetration through the biofilm matrix and kills live bacteria inside mature S. aureus biofilm. PMID:24704337
Bai, Zhi-Qiang; Lin, Xiuping; Wang, Yizhu; Wang, Junfeng; Zhou, Xuefeng; Yang, Bin; Liu, Juan; Yang, Xianwen; Wang, Yi; Liu, Yonghong
Application of plant derived compounds to control fungal spoilage and mycotoxin production in foods.
Food decay by spoilage fungi causes considerable economic losses and constitutes a health risk for consumers due to the potential for fungi to produce mycotoxins. The indiscriminate use of synthetic antifungals has led to the development of resistant strains which has necessitated utilization of higher concentrations, with the consequent increase in toxic residues in food products. Numerous studies have demonstrated that plant extracts contain diverse bioactive components that can control mould growth. The metabolites produced by plants are a promising alternative because plants generate a wide variety of compounds, either as part of their development or in response to stress or pathogen attack. The aim of this article is to summarize the results from the literature on in vitro and in vivo experiments regarding the effects of plant-derived products for controlling fungal growth. Data from research work on the mode of action of these metabolites inside the fungal cell and the influence of abiotic external factors such as pH and temperature are also covered in the present review. Furthermore, an analysis on how the stress factor derived from the presence of plant extracts and essential oils affects secondary metabolism of the fungus, specifically mycotoxin synthesis, is developed. Finally, the effectiveness of using plant-derived compounds in combination with other natural antimicrobials and its application in food using novel technologies is discussed. PMID:23816820
da Cruz Cabral, Lucía; Fernández Pinto, Virginia; Patriarca, Andrea
Some chromatographic characteristics of germination stimulants in plant-derived smoke extracts
Plant-derived smoke extracts stimulate the germination of many different seeds. the present report explains steps to determine some of the chemical characteristics of the compounds concerned. Grand Rapids lettuce seeds were used as a bioassay because smoke-derived extracts overcome their light-sensitivity. The active compounds were partitioned into ethyl acetate, separated by various TLC systems and fractionated by reverse phase HPLC.
J. van Staden; F. E. Drewes; N. A. C. Brown
Molecular Aspects of Polyene- and Sterol-Dependent Pore Formation in Thin Lipid Membranes
Amphotericin B modifies the permeability properties of thin lipid membranes formed from solutions containing sheep red cell phospholipids and cholesterol. At 10-6 M amphotericin B, the DC membrane resistance fell from ?108 to ?102 ohm-cm2, and the membranes became Cl--, rather than Na+-selective; the permeability coefficients for hydrophilic nonelectrolytes increased in inverse relationship to solute size, and the rate of water flow during osmosis increased 30-fold. These changes may be rationalized by assuming that the interaction of amphotericin B with membrane-bound sterol resulted in the formation of aqueous pores. N-acetylamphotericin B and the methyl ester of N-acetylamphotericin B, but not the smaller ring compounds, filipin, rimocidin, and PA-166, produced comparable permeability changes in identical membranes, and amphotericin B and its derivatives produced similar changes in the properties of membranes formed from phospholipid-free sterol solutions. However, amphotericin B did not affect ionic selectivity or water and nonelectrolyte permeability in membranes formed from solutions containing phospholipids and no added cholesterol, or when cholesterol was replaced by either cholesterol palmitate, dihydrotachysterol, epicholesterol, or ?5-cholesten-3-one. Phospholipid-free sterol membranes exposed to amphotericin B or its derivatives were anion-selective, but the degree of Cl- selectivity varied among the compounds, and with the aqueous pH. The data are discussed with regard to, first, the nature of the polyene-sterol interactions which result in pore formation, and second, the functional groups on amphotericin B responsible for membrane anion selectivity.
Dennis, Vincent W.; Stead, Nancy W.; Andreoli, Thomas E.
Characterization of the sterol 14?-demethylases of Fusarium graminearum identifies a novel genus-specific CYP51 function.
CYP51 encodes the cytochrome P450 sterol 14?-demethylase, an enzyme essential for sterol biosynthesis and the target of azole fungicides. In Fusarium species, including pathogens of humans and plants, three CYP51 paralogues have been identified with one unique to the genus. Currently, the functions of these three genes and the rationale for their conservation within the genus Fusarium are unknown. Three Fusarium graminearum CYP51s (FgCYP51s) were heterologously expressed in Saccharomyces cerevisiae. Single and double FgCYP51 deletion mutants were generated and the functions of the FgCYP51s were characterized in vitro and in planta. FgCYP51A and FgCYP51B can complement yeast CYP51 function, whereas FgCYP51C cannot. FgCYP51A deletion increases the sensitivity of F. graminearum to the tested azoles. In ?FgCYP51B and ?FgCYP51BC mutants, ascospore formation is blocked, and eburicol and two additional 14-methylated sterols accumulate. FgCYP51C deletion reduces virulence on host wheat ears. FgCYP51B encodes the enzyme primarily responsible for sterol 14?-demethylation, and plays an essential role in ascospore formation. FgCYP51A encodes an additional sterol 14?-demethylase, induced on ergosterol depletion and responsible for the intrinsic variation in azole sensitivity. FgCYP51C does not encode a sterol 14?-demethylase, but is required for full virulence on host wheat ears. This is the first example of the functional diversification of a fungal CYP51. PMID:23442154
Fan, Jieru; Urban, Martin; Parker, Josie E; Brewer, Helen C; Kelly, Steven L; Hammond-Kosack, Kim E; Fraaije, Bart A; Liu, Xili; Cools, Hans J
Plant-derived synergists of alarm pheromone from turnip aphid, Lipaphis (Hyadaphis) erysimi (Homoptera, Aphididae)
The turnip aphid,Lipaphis (Hyadaphis) erysimi, responds weakly to (E)-ß-farnesene, the main component of the alarm pheromone, but the response is substantially increased by incorporating plant-derived isothiocyanates, identified in aphid volatiles by coupled gas chromatography-single-cell recording.
G. W. Dawson; D. C. Griffiths; J. A. Pickett; L. J. Wadhams; Christine M. Woodcock
Chemometric approach to validating faecal sterols as source tracer for faecal contamination in water.
Faecal sterols detection is a promising method for identifying sources of faecal pollution. In this study, faecal contamination in water samples from point source (sewage treatment plants, chicken farms, quail farms and horse stables) was extracted using the solid phase extraction (SPE) technique. Faecal sterols (coprostanol, cholesterol, stigmasterol, beta-sitosterol and stigmastanol) were selected as parameters to differentiate the source of faecal pollution. The results indicated that coprostanol, cholesterol and beta-sitosterol were the most significant parameters that can be used as source tracers for faecal contamination. Chemometric techniques, such as cluster analysis, principal component analysis and discriminant analysis were applied to the data set on faecal contamination in water from various pollution sources in order to validate the faecal sterols' profiles. Cluster analysis generated three clusters: coprostanol was in cluster 1, cholesterol and beta-sitosterol formed cluster 2, while cluster 3 contained stigmasterol and stigmastanol. Discriminant analysis suggested that coprostanol, cholesterol and beta-sitosterol were the most significant parameters to discriminate between the faecal pollution source. The use of chemometric techniques provides useful and promising indicators in tracing the source of faecal contamination. PMID:19896157
Saim, Norashikin; Osman, Rozita; Sari Abg Spian, Dayang Ratena; Jaafar, Mohd Zuli; Juahir, Hafizan; Abdullah, Md Pauzi; Ghani, Fuzziawati Ab
Derivative Analysis of AVIRIS Hyperspectral Data for the Detection of Plant Stress
NASA Technical Reports Server (NTRS)
A remote sensing campaign was conducted over a U.S. Department of Agriculture test site at Shelton, Nebraska. The test field was set off in blocks that were differentially treated with nitrogen. Four replicates of 0-kg/ha to 200-kg/ha, in 50-kg/ha increments, were present. Low-altitude AVIRIS hyperspectral data were collected over the site in 224 spectral bands. Simultaneously, ground data were collected to support the airborne imagery. In an effort to evaluate published, derivative-based algorithms for the detection of plant stress, different derivative-based approaches were applied to the collected AVIRIS image cube. The results indicate that, given good quality hyperspectral imagery, derivative techniques compare favorably with simple, well known band ratio algorithms for detection of plant stress.
Estep, Lee; Berglund, Judith
Production of an active recombinant thrombomodulin derivative in transgenic tobacco plants and suspension cells.
Thrombomodulin is a membrane-bound protein that plays an active role in the blood coagulation system by binding thrombin and initiating the protein C anticoagulant pathway. Solulin is a recombinant soluble derivative of human thrombomodulin. It is used for the treatment of thrombotic disorders. To evaluate the production of this pharmaceutical protein in plants, expression vectors were generated using four different N-terminal signal peptides. Immunoblot analysis of transiently transformed tobacco leaves showed that intact Solulin could be detected using three of these signal peptides. Furthermore transgenic tobacco plants and BY2 cells producing Solulin were generated. Immunoblot experiments showed that Solulin accumulated to maximum levels of 115 and 27 microg g(-1) plant material in tobacco plants and BY2 cells, respectively. Activity tests performed on the culture supernatant of transformed BY2 cells showed that the secreted Solulin was functional. In contrast, thrombomodulin activity was not detected in total soluble protein extracts from BY2 cells, probably due to inhibitory effects of substances in the cell extract. N-terminal sequencing was carried out on partially purified Solulin from the BY2 culture supernatant. The sequence was identical to that of Solulin produced in Chinese hamster ovary cells, confirming correct processing of the N-terminal signal peptide. We have demonstrated that plants and plant cell cultures can be used as alternative systems for the production of an active recombinant thrombomodulin derivative. PMID:16145833
Schinkel, Helga; Schiermeyer, Andreas; Soeur, Raphael; Fischer, Rainer; Schillberg, Stefan
Cholesterol interaction with recombinant human sterol carrier protein-2
The interaction of human recombinant sterol carrier protein-2 (SCP-2) with sterols was examined. Two independent ligand binding\\u000a methods, Lipidex 1000 binding of [3H]cholesterol and a fluorescent dehydroergosterol binding assay, were used to determine the affinity of SCP-2 for sterols.\\u000a Binding analysis indicated SCP-2 bound [3H]cholesterol and dehydroergosterol with aK\\u000a d of 0.3 and 1.7 ?M, respectively, and suggested the presence
S. M. Colles; J. K. Woodford; D. Moncecchi; S. C. Myers-Payne; L. R. McLean; J. T. Billheimer; F. Schroeder
Kinetics of ? 5,7 -sterol accumulation during growth of Saccharomyces cerevisiae
Saccharomyces cerevisiae accumulates ?5,7-sterols up to 4 mg per g biomass. The differential rate of sterol synthesis continually increases during growth, its value\\u000a only being decreased at sterol levels higher than 30 mg per g biomass. The specific rate of sterol synthesis reaches a broad\\u000a maximum during the growth phase. The gradual sterol accumulation pattern is dominant in cultures growing
?. Novotný; B. B?halová; L. Doležalová; J. Zají?ek
Terpenoids and sterols from some Japanese mushrooms.
Over the past twenty years, our research group has been studying the chemical constituents of mushrooms. From nineteen species, namely, Amanita virgineoides Bas (Amanitaceae), Daedaleopsis tricolor (Bull.: Fr.) Bond. et Sing. (Polyporaceae), Grifolafrondosa (Fr.) S. F. Gray (Polyporaceae), Hericium erinaceum (Bull.: Fr.) Pers. (Hericiaceae), Hypsizigus marmoreus (Peck) Bigelow (Tricholomataceae), Lactarius piperatus (Scop.: Fr.) S. F. Gray (Russulaceae), Lentinula edodes (Berk.) Sing. (Pleurotaceae), Lyophyllyum connatum (Schum.: Fr.) Sing. (Tricholomataceae), Naematoloma sublateritium (Fr.) Karst. (Strophariaceae), Ompharia lapidescens Schroeter (Polyporaceae), Panellus serotinus (Pers.: Fr.) Kuhn. (Tricholomataceae), Pholiota nameko (T. Ito) S. Ito et Imai in Imai (Strophariaceae), Pleurotus eringii (DC.: Fr.) Quel. (Pleurotaceae), Polyporus umbellatus Fries (Polyporaceae), Russula delica Fr. (Russulaceae), Russula sanguinea (Bull.) Fr. (Russulaceae), Sarcodon aspratus (Berk.) S. Ito (Thelephoraceae), Tricholoma matsutake (S. Ito et Imai) Sing. (Tricholomataceae), and Tricholomaportentosum (Fr.) Quel. (Tricholomataceae), we isolated eight new sesquiterpenoids, six new meroterpenoids, three new triterpenoids, and twenty eight new sterols. In this review, structural features of these new compounds are discussed. PMID:24689228
Yaoita, Yasunori; Kikuchi, Masao; Machida, Koichi
Susceptibility of immature Ixodes scapularis (Acari:Ixodidae) to plant-derived acaricides.
Plant-derived acaricides, extracted from various botanical species, and commercially available phytochemicals were evaluated for biological activity against immature Ixodes scapularis (Say) using the disposable pipet method. In addition, residual activity of the plant extracts was determined. Of the 13 plant extracts tested, 9 exhibited biological activity with Alaska yellow cedar, Chamaecyparis nootkatensis (D. Don) Spach., being the most effective against the nymphal ticks (LC50 = 0.151% wt:vol) and eastern red cedar, Juniperus virginiana L., showing the greatest activity against larval ticks (LC50 = .001% wt:vol). The commercially available products were significantly less active than the plant extracts we prepared, but some commercial compounds did exhibit limited activity. Only the Alaska yellow cedar exhibited any residual activity that lasted 21 d after treatment. PMID:9151500
Panella, N A; Karchesy, J; Maupin, G O; Malan, J C; Piesman, J
Mutations in UDP-Glucose:Sterol Glucosyltransferase in Arabidopsis Cause Transparent Testa Phenotype and Suberization Defect in Seeds1[C][W][OA
In higher plants, the most abundant sterol derivatives are steryl glycosides (SGs) and acyl SGs. Arabidopsis (Arabidopsis thaliana) contains two genes, UGT80A2 and UGT80B1, that encode UDP-Glc:sterol glycosyltransferases, enzymes that catalyze the synthesis of SGs. Lines having mutations in UGT80A2, UGT80B1, or both UGT80A2 and UGT8B1 were identified and characterized. The ugt80A2 lines were viable and exhibited relatively minor effects on plant growth. Conversely, ugt80B1 mutants displayed an array of phenotypes that were pronounced in the embryo and seed. Most notable was the finding that ugt80B1 was allelic to transparent testa15 and displayed a transparent testa phenotype and a reduction in seed size. In addition to the role of UGT80B1 in the deposition of flavanoids, a loss of suberization of the seed was apparent in ugt80B1 by the lack of autofluorescence at the hilum region. Moreover, in ugt80B1, scanning and transmission electron microscopy reveals that the outer integument of the seed coat lost the electron-dense cuticle layer at its surface and displayed altered cell morphology. Gas chromatography coupled with mass spectrometry of lipid polyester monomers confirmed a drastic decrease in aliphatic suberin and cutin-like polymers that was associated with an inability to limit tetrazolium salt uptake. The findings suggest a membrane function for SGs and acyl SGs in trafficking of lipid polyester precursors. An ancillary observation was that cellulose biosynthesis was unaffected in the double mutant, inconsistent with a predicted role for SGs in priming cellulose synthesis.
DeBolt, Seth; Scheible, Wolf-Rudiger; Schrick, Kathrin; Auer, Manfred; Beisson, Fred; Bischoff, Volker; Bouvier-Nave, Pierrette; Carroll, Andrew; Hematy, Kian; Li, Yonghua; Milne, Jennifer; Nair, Meera; Schaller, Hubert; Zemla, Marcin; Somerville, Chris
Screening, isolation and optimization of anti-white spot syndrome virus drug derived from marine plants
Objective To screen, isolate and optimize anti-white spot syndrome virus (WSSV) drug derived from various marine floral ecosystems and to evaluate the efficacy of the same in host–pathogen interaction model. Methods Thirty species of marine plants were subjected to Soxhlet extraction using water, ethanol, methanol and hexane as solvents. The 120 plant isolates thus obtained were screened for their in vivo anti-WSSV property in Litopenaeus vannamei. By means of chemical processes, the purified anti-WSSV plant isolate, MP07X was derived. The drug was optimized at various concentrations. Viral and immune genes were analysed using reverse transcriptase PCR to confirm the potency of the drug. Results Nine plant isolates exhibited significant survivability in host. The drug MP07X thus formulated showing 85% survivability in host. The surviving shrimps were nested PCR negative at the end of the 15 d experimentation. The lowest concentration of MP07X required intramuscularly for virucidal property was 10 mg/mL. The oral dosage of 1?000 mg/kg body weight/day survived at the rate of 85%. Neither VP28 nor ie 1 was expressed in the test samples at 42nd hour and 84th hour post viral infection. Conclusions The drug MP07X derived from Rhizophora mucronata is a potent anti-WSSV drug.
Chakraborty, Somnath; Ghosh, Upasana; Balasubramanian, Thangavel; Das, Punyabrata
Seaweed Polysaccharides and Derived Oligosaccharides Stimulate Defense Responses and Protection Against Pathogens in Plants
Plants interact with the environment by sensing "non-self" molecules called elicitors derived from pathogens or other sources. These molecules bind to specific receptors located in the plasma membrane and trigger defense responses leading to protection against pathogens. In particular, it has been shown that cell wall and storage polysaccharides from green, brown and red seaweeds (marine macroalgae) corresponding to ulvans, alginates, fucans, laminarin and carrageenans can trigger defense responses in plants enhancing protection against pathogens. In addition, oligosaccharides obtained by depolymerization of seaweed polysaccharides also induce protection against viral, fungal and bacterial infections in plants. In particular, most seaweed polysaccharides and derived oligosaccharides trigger an initial oxidative burst at local level and the activation of salicylic (SA), jasmonic acid (JA) and/or ethylene signaling pathways at systemic level. The activation of these signaling pathways leads to an increased expression of genes encoding: (i) Pathogenesis-Related (PR) proteins with antifungal and antibacterial activities; (ii) defense enzymes such as pheylalanine ammonia lyase (PAL) and lipoxygenase (LOX) which determine accumulation of phenylpropanoid compounds (PPCs) and oxylipins with antiviral, antifugal and antibacterial activities and iii) enzymes involved in synthesis of terpenes, terpenoids and/or alkaloids having antimicrobial activities. Thus, seaweed polysaccharides and their derived oligosaccharides induced the accumulation of proteins and compounds with antimicrobial activities that determine, at least in part, the enhanced protection against pathogens in plants.
Vera, Jeannette; Castro, Jorge; Gonzalez, Alberto; Moenne, Alejandra
Quantitative determination of sterols and other alcohols in overland flow from grazing land and possible source materials.
Organic marker compounds (biomarkers) can be used to identify the sources of waterborne pollutants. This paper examines sterols and other alcohols in overland flow from pasture-based grazing systems, possible agricultural source materials and water extracts of these source materials as a preliminary step to developing chemical profiles that can be used for tracing pollutants. The biomarkers were quantified using gas chromatography and gas chromatography-mass spectrometry techniques. Analyses of plant material show that some pasture species contain unique compounds, enabling their identification. For example, Arctotheca calendula (capeweed) contains an as yet unidentified compound (Arctotheca m/z 163). Other pasture species that do not contain unique compounds do contain unique ratios of phytol, hexacosanol, octacosanol and 24-ethylcholesterol, enabling their identification. Analyses of faecal samples show that the ratios of sterols to stanols enable faeces to be distinguished from the pasture species, e.g. the ratio of 24-ethylcholesterol to 24-ethylcoprostanol was <1, generally <0.25 for faeces, while for most pasture species this ratio was >4. Using this ratio, qualitative apportioning of the sources of pollutants in overland flow to vegetation or faeces could be performed, but only in extreme cases (i.e. when the ratio <1 or >4). Decaying organic matter and surface soil appear to contain a composite of plant and faecal sterols. Sterols, being sparingly soluble in water and surface active, were not expected to be present in overland flow samples. Surprisingly, cholesterol and 24-ethylcoprostanol were found in both the particulate and filtrate fractions of most overland flow and water extracts of most source materials. Using the ratios of sterols to stanols, particulate organic material in water could be traced back to its broader source, i.e. vegetation or faeces. PMID:15998530
Nash, David; Leeming, Rhys; Clemow, Leigh; Hannah, Murray; Halliwell, David; Allen, David
Potential of Plant-Derived Natural Products in the Treatment of Leukemia and Lymphoma
Hematologic malignancies account for a substantial percentage of cancers worldwide, and the heterogeneity and biological characteristics of leukemias and lymphomas present unique therapeutic challenges. Although treatment options exist for most of these diseases, many types remain incurable and the emergence of drug resistance is pervasive. Thus, novel treatment approaches are essential to improve outcome. Nearly half of the agents used in cancer therapy today are either natural products or derivatives of natural products. The enormous chemical diversity in nature, coupled with millennia of biological selection, has generated a vast and underexplored reservoir of unique chemical structures with biologic activity. This review will describe the investigation and application of natural products derived from higher plants in the treatment of leukemia and lymphoma and the rationale behind these efforts. In addition to the approved vinca alkaloids and the epipodophyllotoxin derivatives, a number of other plant compounds have shown promise in clinical trials and in preclinical investigations. In particular, we will focus on the discovery and biological evaluation of the plant-derived agent silvestrol, which shows potential for additional development as a new therapeutic agent for B-cell malignancies including chronic lymphocytic leukemia.
Lucas, David M.; Still, Patrick C.; Perez, Lynette Bueno; Grever, Michael R.; Kinghorn, A. Douglas
Structural complex of sterol 14?-demethylase (CYP51) with 14?-methylenecyclopropyl-?7-24, 25-dihydrolanosterol[S
Sterol 14?-demethylase (CYP51) that catalyzes the removal of the 14?-methyl group from the sterol nucleus is an essential enzyme in sterol biosynthesis, a primary target for clinical and agricultural antifungal azoles and an emerging target for antitrypanosomal chemotherapy. Here, we present the crystal structure of Trypanosoma (T) brucei CYP51 in complex with the substrate analog 14?-methylenecyclopropyl-?7-24,25-dihydrolanosterol (MCP). This sterol binds tightly to all protozoan CYP51s and acts as a competitive inhibitor of F105-containing (plant-like) T. brucei and Leishmania (L) infantum orthologs, but it has a much stronger, mechanism-based inhibitory effect on I105-containing (animal/fungi-like) T. cruzi CYP51. Depicting substrate orientation in the conserved CYP51 binding cavity, the complex specifies the roles of the contact amino acid residues and sheds new light on CYP51 substrate specificity. It also provides an explanation for the effect of MCP on T. cruzi CYP51. Comparison with the ligand-free and azole-bound structures supports the notion of structural rigidity as the characteristic feature of the CYP51 substrate binding cavity, confirming the enzyme as an excellent candidate for structure-directed design of new drugs, including mechanism-based substrate analog inhibitors.
Hargrove, Tatiana Y.; Wawrzak, Zdzislaw; Liu, Jialin; Waterman, Michael R.; Nes, W. David; Lepesheva, Galina I.
Shape and pharmacophore-based virtual screening to identify potential cytochrome P450 sterol 14?-demethylase inhibitors.
Sterol 14?-demethylase (CYP51) is a cytochrome P450 heme thiolate containing enzyme involved in biosynthesis of membrane sterols, including sterol in animals, ergosterol in fungi, and a variety of C24-modified sterols in plants and protozoa. Several clinical drugs have been developed to reduce the impact of fungal diseases, but their clinical uses have been limited by the emergence of drug resistance and insufficiencies in their antifungal activity. Therefore, in order to identify potential CYP51 inhibitors, we have implemented a virtual screening (VS) protocol by using both phase shape and pharmacophore model (AHHRR) against Asinex, ChemBridge and Maybridge databases. A filtering protocol, including Lipinski filter, number of rotatable bonds and different precisions of molecular docking was applied in hits selection. The results indicated that both shape-based and pharmacophore-based screening yielded the best result with potential inhibitors. The searched compounds were also evaluated with ADME properties, which show excellent pharmacokinetic properties under the acceptable range. We identified potential CYP51 inhibitors for further investigation, they could also be employed to design ligands with enhanced inhibitory potencies and to predict the potencies of analogs to guide synthesis/or prepare synthetic antifungal analogs against CYP51. PMID:23638723
Reddy, Karnati Konda; Singh, Sanjeev Kumar; Tripathi, Sunil Kumar; Selvaraj, Chandrabose; Suryanarayanan, Venkatesan
Sterol Profile for Natural Juices Authentification by GC-MS
A GC-MS analytical method is described for some natural juices analysis. The fingerprint of sterols was used to characterize the natural juice. A rapid liquid-liquid extraction method was used. The sterols were separated on a Rtx-5MS capillary column, 15mx0.25mm, 0.25{mu}m film thickness, in a temperature program from 50 deg. C for 1 min, then ramped at 15 deg. C/min to 300 deg. C and held for 15 min. Identification of sterols and their patterns were used for juice characterization. The sterol profile is a useful approach for confirming the presence of juices of orange, grapefruit, pineapple and passion fruit in compounded beverages and for detecting of adulteration of fruit juices.
Culea, M. [Faculty of Physics, Babes-Bolyai University of Cluj-Napoca (Romania)
Functional convergence of hopanoids and sterols in membrane ordering
Liquid-ordered phases are one of two biochemically active membrane states, which until now were thought to be a unique consequence of the interactions between eukaryotic membrane lipids. The formation of a liquid-ordered phase depends crucially on the ordering properties of sterols. However, it is not known whether this capacity exists in organisms that lack sterols, such as bacteria. We show that diplopterol, the simplest bacterial hopanoid, has similar properties and that hopanoids are bacterial "sterol surrogates" with the ability to order saturated lipids and to form a liquid-ordered phase in model membranes. These observations suggest that the evolution of an ordered biochemically active liquid membrane could have evolved before the oxygenation of Earth's surface and the emergence of sterols.
Saenz, James Peter; Sezgin, Erdinc; Schwille, Petra; Simons, Kai
Characteristics of a New Sterol-nonrequiring Mycoplasma
Two Mycoplasma strains recovered from tissue culture environments were found to grow in complex media devoid of serum or serum fractions containing cholesterol and in a cholesterol-free synthetic medium. Neither strain was capable of synthesizing pigmented carotenoids, although these compounds are present in, and characteristic of, other sterol-nonrequiring mycoplasmas. Serological tests and an analysis of their cell protein patterns obtained by gel electrophoresis indicated that the isolates were similar to each other but distinct from other sterol-nonrequiring serotypes, Mycoplasma laidlawii and M. granularum, as well as from sterol-requiring species. The existence of Mycoplasma other than M. laidlawii and M. granularum without sterol requirements suggested the need for some taxonomic changes in this group of organisms. Images
Tully, Joseph G.; Razin, Shmuel
Lipase-mediated synthesis of water-soluble plant stanol derivatives in tert-butanol.
The effects of solvents with different log P values, and of lipases on the synthesis of water-soluble plant stanol derivatives were investigated. Results showed that conversion in solvents with log P<0.37 was mainly controlled by the hydrophobicity of the solvent and subsequent complete or partial deactivation of the enzyme. The solubility of substrate was the leading factor for the conversion in solvents with log P>0.37. Lipozyme RM IM and tert-butanol was the most suitable biocatalyst and solvent, respectively. The highest yield (>51%) of plant stanyl sorbitol succinate was obtained under the selected conditions: 50 ?mol/mL plant stanyl hemisuccinate, 1:3 molar ratio of plant stanyl hemisuccinate to d-sorbitol, 80 mg/mL 3 Ĺ molecular sieves and 100mg/mL Lipozyme RM IM in tert-butanol, 150 r/min and 55 °C. Fourier transform infrared spectroscopy, mass spectroscopy and nuclear magnetic resonance spectroscopy were adopted to determine the structure of product, suggesting that water-soluble plant stanol derivatives were successfully synthesized. PMID:22464062
He, Wen-Sen; Li, Jing-Jing; Pan, Xiao-Xia; Zhou, Yang; Jia, Cheng-Sheng; Zhang, Xiao-Ming; Feng, Biao
Screening, isolation and optimization of anti-white spot syndrome virus drug derived from terrestrial plants
Objective To screen, isolate and optimize anti-white spot syndrome virus (WSSV) drug derived from various terrestrial plants and to evaluate the efficacy of the same in host–pathogen interaction model. Methods Thirty plants were subjected to Soxhlet extraction using water, ethanol, methanol and hexane as solvents. The 120 plant isolates thus obtained were screened for their in vivo anti–WSSV property in Litopenaeus vannamei. The best anti–WSSV plant isolate, TP22C was isolated and further analyzed. The drug was optimized at various concentrations. Viral and immune genes were analysed using reverse transcriptase PCR to confirm the potency of the drug. Results Seven plant isolates exhibited significant survivability in host. The drug TP22C thus formulated showed 86% survivability in host. The surviving shrimps were nested PCR negative at the end of the 15 d experimentation. The lowest concentration of TP22C required intramuscularly for virucidal property was 10 mg/mL. The oral dosage of 750 mg/kg body weight/day survived at the rate of 86%. Neither VP28 nor ie 1 was expressed in the test samples at 42nd hour and 84th hour post viral infection. Conclusions The drug TP22C derived from Momordica charantia is a potent anti-white spot syndrome virus drug.
Ghosh, Upasana; Chakraborty, Somnath; Balasubramanian, Thangavel; Das, Punyabrata
Virtual screening of plant derived compounds for aldose reductase inhibition using molecular docking.
The role of the aldose reductase in type 2 diabetes is widely described. Therefore, it is of interest to identify plant derived compounds to inhibit its activity. We studied the protein-ligand interaction of 267 compounds from different parts of seven plants (Allium sativum, Coriandrum sativum, Dacus carota, Murrayyakoneigii, Eucalyptus, Calendula officinalis and Lycopersicon esculentum) with aldose reductase as the target protein. Molecular docking and re-scoring of top ten compounds (using GOLD, AutoDock Vina, eHiTS, PatchDock and MEDock) followed by rank-sum technique identified compound allium38 with high binding affinity for aldose reductase. PMID:23275691
Muppalaneni, Naresh Babu; Rao, Allam Appa
Virtual screening of plant derived compounds for aldose reductase inhibition using molecular docking
The role of the aldose reductase in type 2 diabetes is widely described. Therefore, it is of interest to identify plant derived compounds to inhibit its activity. We studied the protein-ligand interaction of 267 compounds from different parts of seven plants (Allium sativum, Coriandrum sativum, Dacus carota, Murrayyakoneigii, Eucalyptus, Calendula officinalis and Lycopersicon esculentum) with aldose reductase as the target protein. Molecular docking and re-scoring of top ten compounds (using GOLD, AutoDock Vina, eHiTS, PatchDock and MEDock) followed by rank-sum technique identified compound allium38 with high binding affinity for aldose reductase.
Muppalaneni, Naresh Babu; Rao, Allam Appa
Sterol Esterification in Yeast: A Two-Gene Process
Unesterified sterol modulates the function of eukaryotic membranes. In human cells, sterol is esterified to a storage form by acyl-coenzyme A (CoA): cholesterol acyl transferase (ACAT). Here, two genes are identified, ARE1 and ARE2, that encode ACAT-related enzymes in yeast. The yeast enzymes are 49 percent identical to each other and exhibit 23 percent identity to human ACAT. Deletion of
Hongyuan Yang; Martin Bard; Debora A. Bruner; Anne Gleeson; Richard J. Deckelbaum; Gordana Aljinovic; Thomas M. Pohl; Rodney Rothstein; Stephen L. Sturley
The Effect of Sterols on Amphotericin B Self-Aggregation in a Lipid Bilayer as Revealed by Free Energy Simulations
Amphotericin B (AmB) is an effective but toxic antifungal drug, known to increase the permeability of the cell membrane, presumably by assembling into transmembrane pores in a sterol-dependent manner. The aggregation of AmB molecules in a phospholipid bilayer is, thus, crucial for the drug's activity. To provide an insight into the molecular nature of this process, here, we report an atomistic molecular dynamics simulation study of AmB head-to-head dimerization in a phospholipid bilayer, a possible early stage of aggregation. To compare the effect of sterols on the thermodynamics of aggregation and the architecture of the resulting AmB-AmB complexes, free energy profiles for the dimerization in ergosterol- or cholesterol-containing and sterol-free membranes are derived from the simulations. These profiles demonstrate that although AmB dimers are formed in all the systems studied, they are significantly less favorable in the bilayer with ergosterol than in the cholesterol-containing or sterol-free ones. We investigate the structural and energetic determinants of this difference and discuss its consequences for the AmB mechanism of action.
Neumann, Anna; Baginski, Maciej; Winczewski, Szymon; Czub, Jacek
Baseline concentrations of faecal sterols and assessment of sewage input into different inlets of Admiralty Bay, King George Island, Antarctica.
The Antarctic region is one of the best preserved environments in the world. However, human activities such as the input of sewage result in the alteration of this pristine site. We report baseline values of faecal sterols in Admiralty Bay, Antarctica. Four sediment cores were collected during the 2006/2007 austral summer at the Ezcurra (THP and BAR), Mackelar (REF) and Martel (BTP) inlets. Concentrations of faecal sterols (coprostanol+epicoprostanol) were <0.16 ?g g(-1), suggesting no sewage contamination and probable "biogenic" contributions for these compounds. Baseline values, calculated using the mean concentration of faecal sterols in core layers for THP, BAR, REF and BTP, were 0.04 ± 0.02, 0.03 ± 0.01, 0.07 ± 0.01 and 0.04 ± 0.02 ?g g(-1), respectively. These results established as natural contributions of faecal sterols, suggesting that these markers can be useful indicators of human-derived faecal input and contributing to monitoring programs to prevent anthropogenic impacts. PMID:24239309
Martins, César C; Aguiar, Sabrina N; Wisnieski, Edna; Ceschim, Liziane M M; Figueira, Rubens C L; Montone, Rosalinda C
The sterol composition of different marine microalgae was examined to determine the utility of sterols as biomarkers to distinguish members of various algal classes. For example, members of the class Dinophyceae possess certain 4-methyl sterols, such as dinosterol, which are rare...
Regulation of partitioned sterol biosynthesis in Saccharomyces cerevisiae.
Using yeast strains with null mutations in structural genes which encode delta-aminolevulinic acid synthetase (HEM1), isozymes of 3-hydroxy-3-methylglutaryl coenzyme A (HMG1 and HMG2), squalene epoxidase (ERG1), and fatty acid delta 9-desaturase (OLE1), we were able to determine the effect of hemes, sterols, and unsaturated fatty acids on both sterol production and the specific activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) in Saccharomyces cerevisiae. We found that the HMGR isozymes direct essentially equal amounts of carbon to the biosynthesis of sterols under heme-competent conditions, despite a huge disparity (57-fold) in the specific activities of the reductases. Our results demonstrate that palmitoleic acid (16:1) acts as a rate-limiting positive regulator and that ergosterol acts as a potent inhibitor of sterol production in strains which possess only the HMGR1 isozyme (HMG1 hmg2). In strains which contain only the HMGR2 isozyme (hmg1 HMG2), sterol production was inhibited by oleic acid (18:1) and to a lesser degree by ergosterol. The specific activities of the two reductases (HMGR1 and HMGR2) were found to be differentially regulated by hemes but not by ergosterol, palmitoleic acid, or oleic acid. The disparate effects of unsaturated fatty acids and sterols on these strains lead us to consider the possibility of separate, compartmentalized isoprenoid pathways in S. cerevisiae.
Casey, W M; Keesler, G A; Parks, L W
Sterols in a unicellular relative of the metazoans
Molecular clocks suggest that animals originated well before they first appear as macroscopic fossils, but geologic tests of these hypotheses have been elusive. A rare steroid hydrocarbon, 24-isopropylcholestane, has been hypothesized to be a biomarker for sponges or their immediate ancestors because of its relatively high abundance in pre-Ediacaran to Early Cambrian sedimentary rocks and oils. Biolipid precursors of this sterane have been reported to be prominent in several demosponges. Whether 24-isopropylcholestane can be interpreted as a sponge (and, hence, animal) biomarker, and so provide clues about early metazoan history, depends on an understanding of the distribution of sterol biosynthesis among animals and their protistan relatives. Accordingly, we characterized the sterol profile of the choanoflagellate Monosiga brevicollis, a representative of the unicellular sister group of animals. M. brevicollis does not produce a candidate sterol precursor for 24-isopropylcholestane under our experimental growth conditions. It does, however, produce a number of other sterols, and comparative genomics confirms its biosynthetic potential to produce the full suite of compounds recovered. Consistent with the phylogenetic position of choanoflagellates, the sterol profile and biosynthetic pathway of M. brevicollis display characteristics of both fungal and poriferan sterol biosynthesis. This is an example in which genomic and biochemical information have been used together to investigate the taxonomic specificity of a fossil biomarker.
Kodner, Robin B.; Summons, Roger E.; Pearson, Ann; King, Nicole; Knoll, Andrew H.
In vivo dry matter and protein digestibility of three plant-derived and four animal-derived feedstuffs and diets for juvenile Australian redclaw, Cherax quadricarinatus
Dry matter and protein digestibility of three plant-derived and four animal-derived feedstuffs and diets in which they were included were evaluated for juvenile Australian redclaw. The ingredients evaluated were: soy paste, textured wheat, sorghum meal, two sardine meals (67% and 58% crude protein), squid meal, and red crab meal. A reference diet was formulated and produced in the CIBNOR nutrition
Alfredo Campańa-Torres; Luis R. Martinez-Cordova; Humberto Villarreal-Colmenares; Roberto Civera-Cerecedo
50 CFR 23.92 - Are any wildlife or plants, and their parts, products, or derivatives, exempt?
Code of Federal Regulations, 2013 CFR
...2013-10-01 false Are any wildlife or plants, and their parts, products, or derivatives...EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS (CONTINUED) CONVENTION ON INTERNATIONAL...Species § 23.92 Are any wildlife or plants, and their parts, products, or...
Plant-Derived Polysaccharide Supplements Inhibit Dextran Sulfate Sodium-Induced Colitis in the Rat
Several plant-derived polysaccharides have been shown to have anti-inflammatory activity in animal models. Ambrotose complex\\u000a and Advanced Ambrotose are dietary supplements that include aloe vera gel, arabinogalactan, fucoidan, and rice starch, all\\u000a of which have shown such activity. This study was designed to evaluate these formulations against dextran sulfate sodium (DSS)-induced\\u000a colitis in rats and to confirm their short-term safety
Lee Koetzner; Gary Grover; Jamie Boulet; Henry I. Jacoby
Plant-Derived Polysaccharide Supplements Inhibit Dextran Sulfate Sodium-Induced Colitis in the Rat
Several plant-derived polysaccharides have been shown to have anti-inflammatory activity in animal models. Ambrotose complex and Advanced Ambrotose are dietary supplements that include aloe vera gel, arabinogalactan, fucoidan, and rice starch, all of which have shown such activity. This study was designed to evaluate these formu- lations against dextran sulfate sodium (DSS)-induced colitis in rats and to confirm their short-term
Lee Koetzner; Gary Grover; Jamie Boulet; Henry I. Jacoby
Herbal plants and their derivatives as growth and health promoters in animal nutrition
The purpose of this review is to summarize the effectiveness, modes of action and commercial application of herbal plants and their derivatives as growth promoters for animal. Feed supplements\\u000a are a group of feed ingredients that can cause a desired animal response in a non-nutrient role such as pH shift, growth,\\u000a or metabolic modifier (Hutjens, 1991). Common feed additives used
Seyed Reza Hashemi; Homa Davoodi
In vitro plant regeneration from callus derived from root explants of Lathyrus sativus
Protocols have been developed for the in vitro production of plants from callus derived from root explants of Lathyrus sativus cv. P-24. Callus and shoot regeneration were achieved only in MS medium supplemented with 10.7 µM naphthaleneacetic acid and an increased concentration of kinetin (0.9 µM for 14 days to 1.4 µM for 18 days) during callusing. The shoots obtained
P. K. Roy; G. K. Barat; S. L. Mehta
Transformation of grape ( Vitis vinifera L.) zygotic-derived somatic embryos and regeneration of transgenic plants
Summary Transgenic grape plants were regenerated from somatic embryos derived from immature zygotic embryos of seedless grape (Vitis vinifera L.) selections. Somatic embryos were bombarded twice with 1 m gold particles using the Biolistic PDS-1000\\/He device (Bio-Rad Laboratories) and then exposed to Agrobacterium tumefaciens strain C58\\/Z707 containing the binary plasmid pGA482GG or pCGN7314. Following cocultivation, secondary embryos were allowed to proliferate
R. Scorza; J. M. Cordts; D. W. Ramming; R. L. Emershad
Dormancy break of celery (Apium graveolens L.) seeds by plant derived smoke extract
Seed dormancy of a highly-dormant cultivar of celery (Apium graveolens L.) was broken by combinations of plant-derived smoke extract or N6-benzyladenine (BA) and gibberellins A4\\/7 (GA4\\/7) in the dark at temperatures between 18 and 26°C. A less dormant cultivar which responded to GA4\\/7 alone showed no additional response to smoke extract or BA. Neither smoke extract nor BA affected either
T. H. Thomas; J. Staden
HIV: a raft-targeting approach for prevention and therapy using plant-derived compounds (review).
It has been widely accepted that HIV-1 enters into and buds out from microdomains known as lipid rafts/caveolae of plasma membranes of infected cells. Since lipid rafts are recognized sites for budding and entry of HIV-1, and since lipids in rafts (including composition/dynamic structure) play a crucial role in modulating the functions of raft-associated signaling proteins and receptors, it has been consistently shown that modulating the composition/structure of lipid rafts have influenced the life cycle of HIV-1 inhibiting its replication. Since anti-retroviral multi-drugs treatment has severe side effects, one of the strategies could be to block the HIV-1 entry and its replication using natural compounds that can target lipid rafts. Dietary and plant-derived compounds have advantage over synthetic drugs exhibiting minimum side effects and are available in cost effective manner. Studies exploring the effects of dietary and plant-derived compounds targeting lipid rafts could be an evolving strategy to control the progression of AIDS. This article is intended to review: (i) composition/structure and conditions for the formation of lipid rafts in plasma membranes, (ii) interaction of HIV-1 with lipid rafts and (iii) to introduce a novel concept that dietary and plant-derived compounds, which can target lipid rafts, could have potential preventive/therapeutic values against the progression of AIDS. More emphasis has been given to the roles of omega-3 fatty acids and plant-derived various triterpenes, especially euphane-types of triterpenes extracted from Neem tree, targeting lipid rafts and its major component cholesterol. PMID:19149536
Verma, S P
Citrus genus plants contain N-methylated tryptamine derivatives and their 5-hydroxylated forms.
The occurrence and distribution in Citrus genus plants of N-methylated derivatives of tryptamine and their 5-hydroxylated forms are reported. Tryptamine, N-methyltryptamine, N,N-dimethyltryptamine, N,N,N-trimethyltryptamine, 5-hydroxytryptamine (serotonin), 5-hydroxy-N-methyltryptamine, 5-hydroxy-N,N-dimethyltryptamine (bufotenine), and 5-hydroxy-N,N,N-trimethyltryptamine (bufotenidine) were quantitated by LC-ESI-MS/MS. Leaves of all citrus plants examined contained N,N,N-trimethyltryptamine, a compound that we first discovered in the bergamot plant. Interestingly, we also found out that all plants examined contained 5-hydroxy-N,N-dimethyltryptamine and 5-hydroxy-N,N,N-trimethyltryptamine, compounds never described so far in the Citrus genus. As N,N,N-trimethyltryptamine and 5-hydroxy-N,N,N-trimethyltryptamine possess nicotine-like activity by exerting their action on acetylcholine receptors, it is conceivable that both represent the arrival point of a biosynthetic pathway aimed to provide Citrus plants with chemical defense against aggressors. This hypothesis is supported by our finding that leaves and seeds, which are more frequently attacked by biotic agents, are the parts of the plant where the highest levels of those compounds were found. PMID:23682903
Servillo, Luigi; Giovane, Alfonso; Balestrieri, Maria Luisa; Casale, Rosario; Cautela, Domenico; Castaldo, Domenico
Long-term effects of sterol depletion in C. elegans: sterol content of synchronized wild-type and mutant populations
Three major long-term effects of sterol depriva- tion in Caenorhabditis elegans are described. 1 ) The life expec- tancy of sterol-deprived wild-type animals is decreased by more than 40%. Similar decreases are found in animals car- rying mutations in the daf-9 , daf-12 , daf-16 , and clk-1 genes, suggesting that previously described aging pathways involv- ing these genes are
Mark Merris; Jessica Kraeft; G. S. Tint; John Lenard
Plant-Derived Phenolics Inhibit the Accrual of Structurally Characterised Protein and Lipid Oxidative Modifications
Epidemiological data suggest that plant-derived phenolics beneficial effects include an inhibition of LDL oxidation. After applying a screening method based on 2,4-dinitrophenyl hydrazine- protein carbonyl reaction to 21 different plant-derived phenolic acids, we selected the most antioxidant ones. Their effect was assessed in 5 different oxidation systems, as well as in other model proteins. Mass-spectrometry was then used, evidencing a heterogeneous effect on the accumulation of the structurally characterized protein carbonyl glutamic and aminoadipic semialdehydes as well as for malondialdehyde-lysine in LDL apoprotein. After TOF based lipidomics, we identified the most abundant differential lipids in Cu++-incubated LDL as 1-palmitoyllysophosphatidylcholine and 1-stearoyl-sn-glycero-3-phosphocholine. Most of selected phenolic compounds prevented the accumulation of those phospholipids and the cellular impairment induced by oxidized LDL. Finally, to validate these effects in vivo, we evaluated the effect of the intake of a phenolic-enriched extract in plasma protein and lipid modifications in a well-established model of atherosclerosis (diet-induced hypercholesterolemia in hamsters). This showed that a dietary supplement with a phenolic-enriched extract diminished plasma protein oxidative and lipid damage. Globally, these data show structural basis of antioxidant properties of plant-derived phenolic acids in protein oxidation that may be relevant for the health-promoting effects of its dietary intake.
Naudi, Alba; Romero, Maria-Paz; Cassanye, Anna; Serrano, Jose C. E.; Arola, Lluis; Valls, Josep; Bellmunt, Maria Josep; Prat, Joan; Pamplona, Reinald; Portero-Otin, Manuel; Motilva, Maria-Jose
Sorption of ammonium and phosphate from aqueous solution by biochar derived from phytoremediation plants*
The study on biochar derived from plant biomass for environmental applications is attracting more and more attention. Twelve sets of biochar were obtained by treating four phytoremediation plants, Salix rosthornii Seemen, Thalia dealbata, Vetiveria zizanioides, and Phragmites sp., sequentially through pyrolysis at 500 °C in a N2 environment, and under different temperatures (500, 600, and 700 °C) in a CO2 environment. The cation exchange capacity and specific surface area of biochar varied with both plant species and pyrolysis temperature. The magnesium (Mg) content of biochar derived from T. dealbata (TC) was obviously higher than that of the other plant biochars. This biochar also had the highest sorption capacity for phosphate and ammonium. In terms of biomass yields, adsorption capacity, and energy cost, T. dealbata biochar produced at 600 °C (TC600) is the most promising sorbent for removing contaminants (N and P) from aqueous solution. Therefore, T. dealbata appears to be the best candidate for phytoremediation application as its biomass can make a good biochar for environmental cleaning.
Zeng, Zheng; Zhang, Song-da; Li, Ting-qiang; Zhao, Feng-liang; He, Zhen-li; Zhao, He-ping; Yang, Xiao-e; Wang, Hai-long; Zhao, Jing; Rafiq, Muhammad Tariq
The role of sterol-C4-methyl oxidase in epidermal biology.
Deficiency of sterol C4 methyl oxidase, encoded by the SC4MOL gene, has recently been described in four patients from three different families. All of the patients presented with microcephaly, congenital cataracts, and growth delay in infancy. The first patient has suffered since the age of six years from severe, diffuse, psoriasiform dermatitis, sparing only her palms. She is now 20 years old. The second patient is a 5 year old girl who has just started to develop dry skin and hair changes. The third and fourth patients are a pair of affected siblings with a severe skin condition since infancy. Quantitative sterol analysis of plasma and skin scales from all four patients showed marked elevation of 4?-methyl- and 4, 4'-dimethylsterols, consistent with a deficiency in the first step of sterol C4 demethylation in cholesterol biosynthesis. Mutations in the SC4MOL have been identified in all of the patients. SC4MOL deficiency is the first autosomal recessive disorder identified in the sterol demethylation complex. Cellular studies with patient-derived fibroblasts have shown a higher mitotic rate than control cells in cholesterol-depleted medium, with increased de novo cholesterol biosynthesis and accumulation of methylsterols. Immunologic analyses of granulocytes and B cells from patients and obligate carriers in the patients' families indicated dysregulation of immune-related receptors. Inhibition of sterol C4 methyl oxidase in human transformed lymphoblasts induced activation of the cell cycle. Additional studies also demonstrated diminished EGFR signaling and disrupted vesicular trafficking in cells from the affected patients. These findings suggest that methylsterols play an important role in epidermal biology by their influence on cell proliferation, intracellular signaling, vesicular trafficking and immune response. SC4MOL is situated within the psoriasis susceptibility locus PSORS9, and may be a genetic risk factor for common skin conditions. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. PMID:24144731
He, Miao; Smith, Laurie D; Chang, Richard; Li, Xueli; Vockley, Jerry
The protein quality control system manages plant defence compound synthesis.
Jasmonates are ubiquitous oxylipin-derived phytohormones that are essential in the regulation of many development, growth and defence processes. Across the plant kingdom, jasmonates act as elicitors of the production of bioactive secondary metabolites that serve in defence against attackers. Knowledge of the conserved jasmonate perception and early signalling machineries is increasing, but the downstream mechanisms that regulate defence metabolism remain largely unknown. Here we show that, in the legume Medicago truncatula, jasmonate recruits the endoplasmic-reticulum-associated degradation (ERAD) quality control system to manage the production of triterpene saponins, widespread bioactive compounds that share a biogenic origin with sterols. An ERAD-type RING membrane-anchor E3 ubiquitin ligase is co-expressed with saponin synthesis enzymes to control the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the rate-limiting enzyme in the supply of the ubiquitous terpene precursor isopentenyl diphosphate. Thus, unrestrained bioactive saponin accumulation is prevented and plant development and integrity secured. This control apparatus is equivalent to the ERAD system that regulates sterol synthesis in yeasts and mammals but that uses distinct E3 ubiquitin ligases, of the HMGR degradation 1 (HRD1) type, to direct destruction of HMGR. Hence, the general principles for the management of sterol and triterpene saponin biosynthesis are conserved across eukaryotes but can be controlled by divergent regulatory cues. PMID:24213631
Pollier, Jacob; Moses, Tessa; González-Guzmán, Miguel; De Geyter, Nathan; Lippens, Saskia; Vanden Bossche, Robin; Marhavý, Peter; Kremer, Anna; Morreel, Kris; Guérin, Christopher J; Tava, Aldo; Oleszek, Wieslaw; Thevelein, Johan M; Campos, Narciso; Goormachtig, Sofie; Goossens, Alain
Plant- and Microbe-Derived Compounds Affect the Expression of Genes Encoding Antifungal Compounds in a Pseudomonad with Biocontrol Activity?
We have investigated the impacts of 63 different low-molecular-weight compounds, most of them plant derived, on the in vitro expression of two antifungal biosynthetic genes by the plant-protecting rhizobacterium Pseudomonas fluorescens CHA0. The majority of the compounds tested affected the expression of one or both antifungal genes. This suggests that biocontrol activity in plant-beneficial pseudomonads is modulated by plant-bacterium signaling.
de Werra, Patrice; Huser, Aurelie; Tabacchi, Raphael; Keel, Christoph; Maurhofer, Monika
Plant-derived auxin plays an accessory role in symptom development upon Rhodococcus fascians infection.
The biotrophic phytopathogen Rhodococcus fascians has a profound impact on plant development, mainly through its principal virulence factors, a mix of synergistically acting cytokinins that induce shoot formation. Expression profiling of marker genes for several auxin biosynthesis routes and mutant analysis demonstrated that the bacterial cytokinins stimulate the auxin biosynthesis of plants via specific targeting of the indole-3-pyruvic acid (IPA) pathway, resulting in enhanced auxin signaling in infected tissues. The double mutant tryptophan aminotransferase 1-1 tryptophan aminotransferase related 2-1 (taa1-1 tar2-1) of Arabidopsis (Arabidopsis thaliana), in which the IPA pathway is defective, displayed a decreased responsiveness towards R. fascians infection, although bacterial colonization and virulence gene expression were not impaired. These observations implied that plant-derived auxin was employed to reinforce symptom formation. Furthermore, the increased auxin production and, possibly, the accumulating bacterial cytokinins in infected plants modified the polar auxin transport so that new auxin maxima were repetitively established and distributed, a process that is imperative for symptom onset and maintenance. Based on these findings, we extend our model of the mode of action of bacterial and plant signals during the interaction between R. fascians and Arabidopsis. PMID:22181713
Stes, Elisabeth; Prinsen, Els; Holsters, Marcelle; Vereecke, Danny
The Arabidopsis dwf7/ste1 mutant is defective in the delta7 sterol C-5 desaturation step leading to brassinosteroid biosynthesis.
Lesions in brassinosteroid (BR) biosynthetic genes result in characteristic dwarf phenotypes in plants. Understanding the regulation of BR biosynthesis demands continued isolation and characterization of mutants corresponding to the genes involved in BR biosynthesis. Here, we present analysis of a novel BR biosynthetic locus, dwarf7 (dwf7). Feeding studies with BR biosynthetic intermediates and analysis of endogenous levels of BR and sterol biosynthetic intermediates indicate that the defective step in dwf7-1 resides before the production of 24-methylenecholesterol in the sterol biosynthetic pathway. Furthermore, results from feeding studies with 13C-labeled mevalonic acid and compactin show that the defective step is specifically the Delta7 sterol C-5 desaturation, suggesting that dwf7 is an allele of the previously cloned STEROL1 (STE1) gene. Sequencing of the STE1 locus in two dwf7 mutants revealed premature stop codons in the first (dwf7-2) and the third (dwf7-1) exons. Thus, the reduction of BRs in dwf7 is due to a shortage of substrate sterols and is the direct cause of the dwarf phenotype in dwf7.
Choe, S; Noguchi, T; Fujioka, S; Takatsuto, S; Tissier, C P; Gregory, B D; Ross, A S; Tanaka, A; Yoshida, S; Tax, F E; Feldmann, K A
A Plant-Derived Morphinan as a Novel Lead Compound Active against Malaria Liver Stages
Background The global spread of multidrug–resistant malaria parasites has led to an urgent need for new chemotherapeutic agents. Drug discovery is primarily directed to the asexual blood stages, and few drugs that are effective against the obligatory liver stages, from which the pathogenic blood infection is initiated, have become available since primaquine was deployed in the 1950s. Methods and Findings Using bioassay-guided fractionation based on the parasite's hepatic stage, we have isolated a novel morphinan alkaloid, tazopsine, from a plant traditionally used against malaria in Madagascar. This compound and readily obtained semisynthetic derivatives were tested for inhibitory activity against liver stage development in vitro (P. falciparum and P. yoelii) and in vivo (P. yoelii). Tazopsine fully inhibited the development of P. yoelii (50% inhibitory concentration [IC50] 3.1 ?M, therapeutic index [TI] 14) and P. falciparum (IC50 4.2 ?M, TI 7) hepatic parasites in cultured primary hepatocytes, with inhibition being most pronounced during the early developmental stages. One derivative, N-cyclopentyl-tazopsine (NCP-tazopsine), with similar inhibitory activity was selected for its lower toxicity (IC50 3.3 ?M, TI 46, and IC50 42.4 ?M, TI 60, on P. yoelii and P. falciparum hepatic stages in vitro, respectively). Oral administration of NCP-tazopsine completely protected mice from a sporozoite challenge. Unlike the parent molecule, the derivative was uniquely active against Plasmodium hepatic stages. Conclusions A readily obtained semisynthetic derivative of a plant-derived compound, tazopsine, has been shown to be specifically active against the liver stage, but inactive against the blood forms of the malaria parasite. This unique specificity in an antimalarial drug severely restricts the pressure for the selection of drug resistance to a parasite stage limited both in numbers and duration, thus allowing researchers to envisage the incorporation of a true causal prophylactic in malaria control programs.
Carraz, Maelle; Jossang, Akino; Franetich, Jean-Francois; Siau, Anthony; Ciceron, Liliane; Hannoun, Laurent; Sauerwein, Robert; Frappier, Francois; Rasoanaivo, Philippe; Snounou, Georges; Mazier, Dominique
Plant-derived leading compounds for chemotherapy of human immunodeficiency virus (HIV) infection.
Many compounds of plant origin have been identified that inhibit different stages in the replication cycle of human immunodeficiency virus (HIV): 1) virus adsorption: chromone alkaloids (schumannificine), isoquinoline alkaloids (michellamines), sulphated polysaccharides and polyphenolics, flavonoids, coumarins (glycocoumarin, licopyranocoumarin) phenolics (caffeic acid derivatives, galloyl acid derivatives, catechinic acid derivatives), tannins and triterpenes (glycyrrhizin and analogues, soyasaponin and analogues); 2) virus-cell fusion: lectins (mannose- and N-acetylglucosamine-specific) and triterpenes (betulinic acid and analogues); 3) reverse transcription; alkaloids (benzophenanthridines, protoberberines, isoquinolines, quinolines), coumarins (calanolides and analogues), flavonoids, phloroglucinols, lactones (protolichesterinic acid), tannins, iridoids (fulvoplumierin) and triterpenes; 4) integration: coumarins (3-substituted-4-hydroxycoumarins), depsidones, O-caffeoyl derivatives, lignans (arctigenin and analogues) and phenolics (curcumin); 5) translation: single chain ribosome inactivating proteins (SCRIP's); 6) proteolytic cleavage (protease inhibition): saponins (ursolic and maslinic acids), xanthones (mangostin and analogues) and coumarins; 7) glycosylation: alkaloids including indolizidines (castanospermine and analogues), piperidines (1-deoxynojirimicin and analogues) and pyrrolizidines (australine and analogues); 8) assembly/release: naphthodianthrones (hypericin and pseudohypericin), photosensitisers (terthiophenes and furoisocoumarins) and phospholipids. The target of action of several anti-HIV substances including alkaloids (O-demethyl-buchenavianine, papaverine), polysaccharides (acemannan), lignans (intheriotherins, schisantherin), phenolics (gossypol, lignins, catechol dimers such as peltatols, naphthoquinones such as conocurvone) and saponins (celasdin B, Gleditsia and Gymnocladus saponins), has not been elucidated or does not fit in the proposed scheme. Only a very few of these plant-derived anti-HIV products have been used in a limited number of patients suffering from AIDS viz. glycyrrhizin, papaverine, trichosanthin, castanospermine, N-butyl-1-deoxynojirimicin and acemannan. PMID:9525100
Vlietinck, A J; De Bruyne, T; Apers, S; Pieters, L A
Refuse derived soluble bio-organics enhancing tomato plant growth and productivity
Highlights: Black-Right-Pointing-Pointer Municipal bio-wastes are a sustainable source of bio-based products. Black-Right-Pointing-Pointer Refuse derived soluble bio-organics promote chlorophyll synthesis. Black-Right-Pointing-Pointer Refuse derived soluble bio-organics enhance plant growth and fruit ripening rate. Black-Right-Pointing-Pointer Sustainable chemistry exploiting urban refuse allows sustainable development. Black-Right-Pointing-Pointer Chemistry, agriculture and the environment benefit from biowaste technology. - Abstract: Municipal bio-refuse (CVD), containing kitchen wastes, home gardening residues and public park trimmings, was treated with alkali to yield a soluble bio-organic fraction (SBO) and an insoluble residue. These materials were characterized using elemental analysis, potentiometric titration, and 13C NMR spectroscopy, and then applied as organic fertilizers to soil for tomato greenhouse cultivation. Their performance was compared with a commercial product obtained from animal residues. Plant growth, fruit yield and quality, and soil and leaf chemical composition were the selected performance indicators. The SBO exhibited the best performance by enhancing leaf chlorophyll content, improving plant growth and fruit ripening rate and yield. No product performance-chemical composition relationship could be assessed. Solubility could be one reason for the superior performance of SBO as a tomato growth promoter. The enhancement of leaf chlorophyll content is discussed to identify a possible link with the SBO photosensitizing properties that have been demonstrated in other work, and thus with photosynthetic performance.
Sortino, Orazio [Dipartimento di Scienze Agronomiche Agrochimiche e delle Produzioni Animali, Universita degli Studi di Catania, Via Valdisavoia 5, 95123 Catania (Italy); Dipasquale, Mauro [Dipartimento di Chimica, Universita di Torino, Via P. Giuria 7, 10125 Torino (Italy); Montoneri, Enzo, E-mail: email@example.com [Dipartimento di Chimica, Universita di Torino, Via P. Giuria 7, 10125 Torino (Italy); Tomasso, Lorenzo; Perrone, Daniele G. [Dipartimento di Chimica, Universita di Torino, Via P. Giuria 7, 10125 Torino (Italy); Vindrola, Daniela; Negre, Michele; Piccone, Giuseppe [Dipartimento di Valorizzazione e Protezione delle Risorse Agroforestali, Universita di Torino, Via L. da Vinci 44, 10095 Grugliasco (Italy)
A new arginase enzymatic reactor: development and application for the research of plant-derived inhibitors.
This work was dedicated to the development of a new micro immobilized enzyme reactor (IMER) by using an in situ procedure. Arginase was covalently immobilized on an ethylenediamine (EDA) monolithic convective interaction media (CIM) disk (12mm × 3mm i.d.) previously derivatized with glutaraldehyde. The activity of this IMER was investigated by inserting this micro-IMER in a HPLC system. The effect of the arginase inhibitors was evaluated by the simultaneous injection of each inhibitor with the nitro guanidino benzene (NGB) substrate. The relative IC50 values were found in agreement with those derived by the conventional spectrometric method. This arginase micro-IMER system was also used to study the effects of plant-derived products on the arginase activity. The pet ether extract from the stem bark of the plant Ficus glomerata Roxob. and the procyanidin oligomers of cocoa and chocolate inhibit the arginase activity. Our results confirmed the direct effect of some plant extracts on the arginase activity and their interest in therapies for treating several NO-dependent smooth disorders. PMID:21310573
André, Claire; Herlem, Guillaume; Gharbi, Tijani; Guillaume, Yves Claude
Inhibition of tumor growth by plant-derived mAb
The tumor-associated antigen EpCAM (GA733-2) is a highly expressed target on adenocarcinoma cells, as defined by murine mAb CO17-1A. We recently developed a transgenic plant system for the safe and inexpensive production of large quantities of mAb CO17-1A as a future source of clinical-grade protein. Although the glycosylation pattern of plant-derived mAb (mAbP) CO17-1A differs considerably from that of the mammalian-derived mAb (mAbM), we show here that the biological activity of both mAbs is quite similar. mAbP heavy and light chains assembled to bind the recombinant antigen GA733-2E and specifically bound to human SW948 colorectal carcinoma cells expressing the antigen GA733-2 to the same extent as mAbM. mAbP was as effective as mAbM CO17-1A in inhibiting tumor growth of xenotransplanted SW948 cells in nude mice. These results suggest the promise of transgenic plants as a useful alternative way to produce full-size mAb for cancer immunotherapy.
Ko, Kisung; Steplewski, Zenon; Glogowska, Magdalena; Koprowski, Hilary
Herbal plants and their derivatives as growth and health promoters in animal nutrition.
The purpose of this review is to summarize the effectiveness, modes of action and commercial application of herbal plants and their derivatives as growth promoters for animal. Feed supplements are a group of feed ingredients that can cause a desired animal response in a non-nutrient role such as pH shift, growth, or metabolic modifier (Hutjens, 1991). Common feed additives used in animal diets include immunostimulators, antimicrobials, antioxidants, pH control agents and enzymes. Herbal plants, are a new class of growth promoters and in recent years this feed additives have gained extensive attention in the feed industry. They are a wide variety of herbs, spices, and products derived thereof, and are mainly essential oils. Although numerous reports have demonstrated antioxidative and antimicrobial and immune stimulation efficacy in vitro, respective experimental in vivo evidence is still quite limited. A limited number of experimental comparisons of herbal plants feed additives with antibiotics or organic acid have suggested similar effects on the animal gut microflora. Gut microflora has significant effects on host nutrition, health, and growth performance by interacting with nutrient utilization and the development of gut system of the host. In addition, some phytogenic compounds seem to promote intestinal mucus production. However, the future of using herbs in animal feeding will in great measure depend on the knowledge of chemical structure, their value and characteristics of practical herbs or their extract physiological needs and well-being of animal, and, above all on consumer's preferences and expectations. PMID:21213046
Hashemi, Seyed Reza; Davoodi, Homa
Exserolides A-F, new isocoumarin derivatives from the plant endophytic fungus Exserohilum sp.
Six new isocoumarin derivatives, exserolides A-F (1-6), were isolated from solid cultures of the plant endophytic fungus Exserohilum sp., together with four known metabolites (7-10). The structures of 1-6 were elucidated primarily by NMR experiments. The absolute configuration of the C-3 methine carbon in 1-5 was deduced via the circular dichroism data, whereas that of the 1,3-diol moiety in 6 was assigned from the (1)H NMR data of its (R)- and (S)-MTPA diesters. Compounds 3 and 9 showed antifungal activity against the plant pathogen Fusarium oxysporum, whereas 6 displayed significant inhibitory effects against a small panel of bacteria. PMID:24752143
Li, Ruxin; Chen, Shenxi; Niu, Shubin; Guo, Liangdong; Yin, Jun; Che, Yongsheng
Central cell-derived peptides regulate early embryo patterning in flowering plants.
Plant embryogenesis initiates with the establishment of an apical-basal axis; however, the molecular mechanisms accompanying this early event remain unclear. Here, we show that a small cysteine-rich peptide family is required for formation of the zygotic basal cell lineage and proembryo patterning in Arabidopsis. EMBRYO SURROUNDING FACTOR 1 (ESF1) peptides accumulate before fertilization in central cell gametes and thereafter in embryo-surrounding endosperm cells. Biochemical and structural analyses revealed cleavage of ESF1 propeptides to form biologically active mature peptides. Further, these peptides act in a non-cell-autonomous manner and synergistically with the receptor-like kinase SHORT SUSPENSOR to promote suspensor elongation through the YODA mitogen-activated protein kinase pathway. Our findings demonstrate that the second female gamete and its sexually derived endosperm regulate early embryonic patterning in flowering plants. PMID:24723605
Costa, Liliana M; Marshall, Eleanor; Tesfaye, Mesfin; Silverstein, Kevin A T; Mori, Masashi; Umetsu, Yoshitaka; Otterbach, Sophie L; Papareddy, Ranjith; Dickinson, Hugh G; Boutiller, Kim; VandenBosch, Kathryn A; Ohki, Shinya; Gutierrez-Marcos, José F
Intracellular Reprogramming of Expression, Glycosylation, and Function of a Plant-Derived Antiviral Therapeutic Monoclonal Antibody
Plant genetic engineering, which has led to the production of plant-derived monoclonal antibodies (mAbPs), provides a safe and economically effective alternative to conventional antibody expression methods. In this study, the expression levels and biological properties of the anti-rabies virus mAbP SO57 with or without an endoplasmic reticulum (ER)-retention peptide signal (Lys-Asp-Glu-Leu; KDEL) in transgenic tobacco plants (Nicotiana tabacum) were analyzed. The expression levels of mAbP SO57 with KDEL (mAbPK) were significantly higher than those of mAbP SO57 without KDEL (mAbP) regardless of the transcription level. The Fc domains of both purified mAbP and mAbPK and hybridoma-derived mAb (mAbH) had similar levels of binding activity to the Fc?RI receptor (CD64). The mAbPK had glycan profiles of both oligomannose (OM) type (91.7%) and Golgi type (8.3%), whereas the mAbP had mainly Golgi type glycans (96.8%) similar to those seen with mAbH. Confocal analysis showed that the mAbPK was co-localized to ER-tracker signal and cellular areas surrounding the nucleus indicating accumulation of the mAbP with KDEL in the ER. Both mAbP and mAbPK disappeared with similar trends to mAbH in BALB/c mice. In addition, mAbPK was as effective as mAbH at neutralizing the activity of the rabies virus CVS-11. These results suggest that the ER localization of the recombinant mAbP by KDEL reprograms OM glycosylation and enhances the production of the functional antivirus therapeutic antibody in the plant.
Lee, Kyung-Jin; Kim, Young-Kwan; So, Yang-Kang; Ryu, Jae-Sung; Oh, Seung-Han; Han, Yeon-Soo; Ko, Kinarm; Choo, Young-Kug; Park, Sung-Joo; Brodzik, Robert; Lee, Kyoung-Ki; Oh, Doo-Byoung; Hwang, Kyung-A; Koprowski, Hilary; Lee, Yong Seong; Ko, Kisung
Spatiotemporal analysis of endocytosis and membrane distribution of fluorescent sterols in living cells
Distribution and dynamics of cholesterol in the plasma membrane as well as internalization pathways for sterol from the cell\\u000a surface are of great cell biological interest. Here, UV-sensitive wide field microscopy of the intrinsically fluorescent sterols,\\u000a dehydroergosterol (DHE) and cholestatrienol (CTL) combined with advanced image analysis were used to study spatiotemporal\\u000a sterol distribution in living macrophages, adipocytes and fibroblasts. Sterol
Daniel Wüstner; Nils J. Fćrgeman
Liver fatty acid binding protein enhances sterol transfer by membrane interaction
Among the large family of fatty acid binding proteins, the liver L-FABP is unique in that it not only binds fatty acids but also interacts with sterols to enhance sterol transfer between membranes. Nevertheless, the mechanism whereby L-FABP potentiates intermembrane sterol transfer is unknown. Both fluorescence and dialysis data indicate L-FABP mediated sterol transfer between L-cell fibroblast plasma membranes occurs
Judith K. Woodford; William D. Behnke; Friedhelm Schroeder
Yeast oxysterol-binding proteins: sterol transporters or regulators of cell polarization?
Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) are a conserved family of soluble cytoplasmic proteins that\\u000a can bind sterols, translocate between membrane compartments, and affect sterol trafficking. These properties make ORPs attractive\\u000a candidates for lipid transfer proteins (LTPs) that directly mediate nonvesicular sterol transfer to the plasma membrane. To\\u000a test whether yeast ORPs (the Osh proteins) are sterol LTPs, we
Christopher T. Beh; Gabriel Alfaro; Giselle Duamel; David P. Sullivan; Michael C. Kersting; Shubha Dighe; Keith G. Kozminski; Anant K. Menon
Effect of sterol structure on molecular interactions and lateral domain formation in monolayers containing dipalmitoyl phosphatidylcholine
Molecular associations between different sterols and dipalmitoyl phosphatidylcholine (DPPC) were examined in monolayers at the air\\/water interface. The sterols examined included cholesterol, 5-cholesten-3-one, 4-cholesten-3?-ol, 4-cholesten-3-one, cholesteryl acetate, and cholesteryl methyl-and ethyl ether. Information about the long-range order in pure sterol monolayers, as well as lateral domain-formation in mixed sterol\\/DPPC monolayers was obtained from the lateral miscibility or distribution of NBD-cholesterol
J. Peter Slotte
Targeting Trypanosoma cruzi Sterol 14?-Demethylase (CYP51)
There are at least two obvious features that must be considered upon targeting specific metabolic pathways/enzymes for drug development: the pathway must be essential and the enzyme must allow the design of pharmacologically useful inhibitors. Here, we describe Trypanosoma cruzi sterol 14?-demethylase as a promising target for anti-Chagasic chemotherapy. The use of anti-fungal azoles, which block sterol biosynthesis and therefore membrane formation in fungi, against the protozoan parasite has turned out to be highly successful: a broad spectrum anti-fungal drug, the triazole compound posaconazole, is now entering phase II clinical trials for treatment of Chagas disease. This review summarizes comparative information on anti-fungal azoles and novel inhibitory scaffolds selective for Trypanosomatidae sterol 14?-demethylase through the lens of recent structure/functional characterization of the target enzyme. We believe our studies open wide opportunities for rational design of novel, pathogen-specific and therefore more potent and efficient anti-trypanosomal drugs.
Lepesheva, Galina I.; Villalta, Fernando; Waterman, Michael R.
Characterization of fatty alcohol and sterol fractions in olive tree.
The determination of sterols and fatty alcohols is a part of the study of the metabolomic profile of the unsaponifiable fraction in olive tree. Leaves and drupes from three varieties of olive tree (Arbequina, Picual, and Manzanilla) were used. The content of the target compounds was studied in five ripeness stages and three harvesting periods for olive drupes and leaves, respectively. A method based on ultrasound-assisted extraction and derivatization for the individual identification and quantitation of sterols and fatty alcohols, involving chromatographic separation and mass spectrometry detection by selected ion monitoring, was used. The concentrations of alcohols and sterols in the drupes ranged between 0.1 and 1086.9 mug/g and between 0.1 and 5855.3 mug/g, respectively, which are higher than in leaves. Statistical studies were developed to show the relationship between the concentration of the target analytes and variety, ripeness stage, and harvesting period. PMID:20550122
Orozco-Solano, Mara; Ruiz-Jimenez, José; Luque De Castro, María D
Simultaneous Effects of Light Intensity and Phosphorus Supply on the Sterol Content of Phytoplankton
Sterol profiles of microalgae and their change with environmental conditions are of great interest in ecological food web research and taxonomic studies alike. Here, we investigated effects of light intensity and phosphorus supply on the sterol content of phytoplankton and assessed potential interactive effects of these important environmental factors on the sterol composition of algae. We identified sterol contents of four common phytoplankton genera, Scenedesmus, Chlamydomonas, Cryptomonas and Cyclotella, and analysed the change in sterol content with varying light intensities in both a high-phosphorus and a low-phosphorus approach. Sterol contents increased significantly with increasing light in three out of four species. Phosphorus-limitation reversed the change of sterol content with light intensity, i.e., sterol content decreased with increasing light at low phosphorus supply. Generally sterol contents were lower in low-phosphorus cultures. In conclusion, both light and phosphorus conditions strongly affect the sterol composition of algae and hence should be considered in ecological and taxonomic studies investigating the biochemical composition of algae. Data suggest a possible sterol limitation of growth and reproduction of herbivorous crustacean zooplankton during summer when high light intensities and low phosphorus supply decrease sterol contents of algae.
Piepho, Maike; Martin-Creuzburg, Dominik; Wacker, Alexander
Specific Sterols Required for the Internalization Step of Endocytosis in Yeast
Sterols are major components of the plasma membrane, but their functions in this membrane are not well understood. We isolated a mutant defective in the internalization step of endocytosis in a gene (ERG2) encoding a C-8 sterol isomerase that acts in the late part of the ergosterol biosynthetic pathway. In the absence of Erg2p, yeast cells accumulate sterols structurally different
Alan L. Munn; Antje Heese-Peck; Brian J. Stevenson; Harald Pichler; Howard Riezman
Simultaneous effects of light intensity and phosphorus supply on the sterol content of phytoplankton.
Sterol profiles of microalgae and their change with environmental conditions are of great interest in ecological food web research and taxonomic studies alike. Here, we investigated effects of light intensity and phosphorus supply on the sterol content of phytoplankton and assessed potential interactive effects of these important environmental factors on the sterol composition of algae. We identified sterol contents of four common phytoplankton genera, Scenedesmus, Chlamydomonas, Cryptomonas and Cyclotella, and analysed the change in sterol content with varying light intensities in both a high-phosphorus and a low-phosphorus approach. Sterol contents increased significantly with increasing light in three out of four species. Phosphorus-limitation reversed the change of sterol content with light intensity, i.e., sterol content decreased with increasing light at low phosphorus supply. Generally sterol contents were lower in low-phosphorus cultures. In conclusion, both light and phosphorus conditions strongly affect the sterol composition of algae and hence should be considered in ecological and taxonomic studies investigating the biochemical composition of algae. Data suggest a possible sterol limitation of growth and reproduction of herbivorous crustacean zooplankton during summer when high light intensities and low phosphorus supply decrease sterol contents of algae. PMID:21209879
Piepho, Maike; Martin-Creuzburg, Dominik; Wacker, Alexander
Structural and Functional Analyses of a Sterol Carrier Protein in Spodoptera litura
Backgrounds In insects, cholesterol is one of the membrane components in cells and a precursor of ecdysteroid biosynthesis. Because insects lack two key enzymes, squalene synthase and lanosterol synthase, in the cholesterol biosynthesis pathway, they cannot autonomously synthesize cholesterol de novo from simple compounds and therefore have to obtain sterols from their diet. Sterol carrier protein (SCP) is a cholesterol-binding protein responsible for cholesterol absorption and transport. Results In this study, a model of the three-dimensional structure of SlSCPx-2 in Spodoptera litura, a destructive polyphagous agricultural pest insect in tropical and subtropical areas, was constructed. Docking of sterol and fatty acid ligands to SlSCPx-2 and ANS fluorescent replacement assay showed that SlSCPx-2 was able to bind with relatively high affinities to cholesterol, stearic acid, linoleic acid, stigmasterol, oleic acid, palmitic acid and arachidonate, implying that SlSCPx may play an important role in absorption and transport of these cholesterol and fatty acids from host plants. Site-directed mutation assay of SlSCPx-2 suggests that amino acid residues F53, W66, F89, F110, I115, T128 and Q131 are critical for the ligand-binding activity of the SlSCPx-2 protein. Virtual ligand screening resulted in identification of several lead compounds which are potential inhibitors of SlSCPx-2. Bioassay for inhibitory effect of five selected compounds showed that AH-487/41731687, AG-664/14117324, AG-205/36813059 and AG-205/07775053 inhibited the growth of S. litura larvae. Conclusions Compounds AH-487/41731687, AG-664/14117324, AG-205/36813059 and AG-205/07775053 selected based on structural modeling showed binding affinity to SlSCPx-2 protein and inhibitory effect on the growth of S. litura larvae.
Xu, Rui; Zheng, Sichun; He, Hongwu; Wan, Jian; Feng, Qili
Variable Contribution of Soil and Plant Derived Carbon to Dissolved Organic Matter
NASA Astrophysics Data System (ADS)
The seasonal variation in the amount and sources of dissolved organic matter (DOM) in soil profiles was investigated. In general DOM in soil solution can evolve from the decomposition and mobilization of soil organic matter (SOM), dissolution of dead microbial cells or from the input of plant material such as root exudates or decomposing litter. Here we used vegetation change from C3 to C4 plants to quantify the plant derived carbon in DOM. In 2002 an agricultural field was converted to an experimental grass land. The average carbon isotope value of SOM was -26.5 per mill (sd = 0.2) for the plough horizon. On two independent plots, each 10 x 20 m, we used Amaranthus retroflexus as C4 plant with a carbon isotope label of 13.0 per mill to distinguish unlabeled SOM and plant derived carbon sources. To quantify the contribution of litter input on DOM formation we applied a split plot design. One half had no litter and the other half double amount of above ground litter. Soil water was collected in 10, 20 and 30 cm depth biweekly and DOM concentrations in solution and carbon isotope ratios of the freeze dried and decarbonized material were investigated. During winter uniform concentrations of DOM of about 7 mg/l were measured throughout all depth and treatments. In spring when soil temperatures increase and water availability decreases DOM concentrations increased with similar rates in all depth. Even in the second year of Amaranth growth the carbon isotope ratios of DOM in winter and spring had no C4 signal. The carbon isotope ratios of -26 to -27 per mill suggest SOM as carbon source and contradict a contribution of root exudates to the DOM pool. During summer almost no soil solution was collected. After rewetting in fall DOM concentrations up to 50 mg/l in 10 cm depth and up to 35 mg/l in deeper layers were found. These high concentrations held carbon isotope signals from -25 to -26.5 per mill contradicting carbon input from plant material. With ongoing wetting of the soil the carbon isotope ratios suddenly increased up to -21.7 per mill on the double litter plots and to -24 per mill on no litter plots. However, this signal was not detected in 30 cm depth. Keeling plots proved that the major part of the DOM comes from SOM. In fall and early winter only 36 % and 19 % of plant derived carbon were found in the double litter and no litter plots, respectively. Our results suggest that carbon of the SOM pool is the major source for carbon in DOM. In the spring season root exudates seem to be completely respired by soil organisms suggesting that root and rhizosphere respiration are the same respiratory pool. Only in fall the decomposition of plant litter contributed to carbon in DOM. However, this carbon source is already exhausted in the next spring. In consequence our results may indicate that stored soil carbon is more active than thought and that DOM transport might be a key process to understand carbon sequestration.
Steinbeiss, S.; Gleixner, G.
Protein Mediators of Sterol Transport Across Intestinal Brush Border Membrane
Dysregulation of cholesterol balance contributes significantly to atherosclerotic cardiovascular disease (ASCVD), the leading cause of death in the United States. The intestine has the unique capability to act as a gatekeeper for entry of cholesterol into the body, and inhibition of intestinal cholesterol absorption is now widely regarded as an attractive non-statin therapeutic strategy for ASCVD prevention. In this chapter we discuss the current state of knowledge regarding sterol transport across the intestinal brush border membrane. The purpose of this work is to summarize substantial progress made in the last decade in regards to protein-mediated sterol trafficking, and to discuss this in the context of human disease.
Brown, J. Mark; Yu, Liqing
Sterol Biosynthesis Pathway as Target for Anti-trypanosomatid Drugs
Sterols are constituents of the cellular membranes that are essential for their normal structure and function. In mammalian cells, cholesterol is the main sterol found in the various membranes. However, other sterols predominate in eukaryotic microorganisms such as fungi and protozoa. It is now well established that an important metabolic pathway in fungi and in members of the Trypanosomatidae family is one that produces a special class of sterols, including ergosterol, and other 24-methyl sterols, which are required for parasitic growth and viability, but are absent from mammalian host cells. Currently, there are several drugs that interfere with sterol biosynthesis (SB) that are in use to treat diseases such as high cholesterol in humans and fungal infections. In this review, we analyze the effects of drugs such as (a) statins, which act on the mevalonate pathway by inhibiting HMG-CoA reductase, (b) bisphosphonates, which interfere with the isoprenoid pathway in the step catalyzed by farnesyl diphosphate synthase, (c) zaragozic acids and quinuclidines, inhibitors of squalene synthase (SQS), which catalyzes the first committed step in sterol biosynthesis, (d) allylamines, inhibitors of squalene epoxidase, (e) azoles, which inhibit C14?-demethylase, and (f) azasterols, which inhibit ?24(25)-sterol methyltransferase (SMT). Inhibition of this last step appears to have high selectivity for fungi and trypanosomatids, since this enzyme is not found in mammalian cells. We review here the IC50 values of these various inhibitors, their effects on the growth of trypanosomatids (both in axenic cultures and in cell cultures), and their effects on protozoan structural organization (as evaluted by light and electron microscopy) and lipid composition. The results show that the mitochondrial membrane as well as the membrane lining the protozoan cell body and flagellum are the main targets. Probably as a consequence of these primary effects, other important changes take place in the organization of the kinetoplast DNA network and on the protozoan cell cycle. In addition, apoptosis-like and autophagic processes induced by several of the inhibitors tested led to parasite death.
de Souza, Wanderley; Rodrigues, Juliany Cola Fernandes
Role of plant stanol derivatives in the modulation of cholesterol metabolism and liver gene expression in mice.
The present study was to evaluate the cholesterol-lowering effect of two novel plant stanol derivatives and its potential molecular mechanism in hyper-cholesterol mice induced by a high-cholesterol diet. Results showed that oral administration of plant stanyl hemisuccinate (2×, 5×) and plant stanyl sorbitol succinate (2×, 5×) effectively attenuated the serum total cholesterol and low density lipoprotein cholesterol levels, while had no effect on the serum triacylglycerol and high density lipoprotein cholesterol. And plant stanol derivatives decreased liver cholesterol concentration and increased faecal cholesterol output. Meanwhile, both plant stanyl hemisuccinate and plant stanyl sorbitol succinate could remarkably promote liver X receptor alpha (LXR?) expression, and increased cholesterol 7?-hydroxylase (CYP7A1) expression and faecal total bile acid output to varying degrees. These results suggested two novel plant stanol derivatives possessed hypocholesterolemic effect, and the cholesterol-lowering action of plant stanol derivatives may be through activating the potential LXR?-CYP7A1-bile acid excretion pathway. PMID:23578608
He, Wen-Sen; Wang, Mei-Gui; Pan, Xiao-Xia; Li, Jing-Jing; Jia, Cheng-Sheng; Zhang, Xiao-Ming; Feng, Biao
Detection of Somaclonal Variations in Tissue Culture-Derived Date Palm Plants Using Isoenzyme Analysis and RAPD Fingerprints
Isoenzyme analysis and activities of peroxidase (PER), polyphenol oxidase (POD) and glutamate oxaloacetate (GOT) and randomly amplified polymorphic DNA (RAPD) fingerprints were used to analyze somaclonal variations in tissue culture-derived date palm plants. The frequency of somaclonal variations was found to be age dependent. Similar isoenzyme patterns for PER and GOT were detected in all analyzed plants. However, variations in
M. M. Saker; S. A. Bekheet; H. S. Taha; A. S. Fahmy; H. A. Moursy
Down-regulation of hormone-sensitive lipase in sterol ester-laden J774.2 macrophages.
The development of atherosclerotic plaques in arteries is a key step in atherogenesis, with cholesterol ester accumulation in macrophage-derived foam cells being recognized as a major pathogenic event in this process. In this study, the mouse macrophage cell line J774.2 was induced to accumulate intracellular sterol esters by incubation with 25-hydroxycholesterol in the presence of oleic acid. The accumulation of sterol esters in these cells was found to be accompanied by a marked decrease in the activity of the enzyme responsible for their hydrolysis, namely hormone-sensitive lipase (HSL); Western blotting studies revealed a corresponding decrease in the levels of the HSL polypeptide. Similar findings were obtained after incubation with oxidized low-density lipoprotein or very-low-density lipoprotein. These findings suggest that down-regulation of the expression of HSL is important in cholesterol ester accumulation in macrophages.
Jepson, C A; Harrison, J A; Kraemer, F B; Yeaman, S J
Cytochrome P450 CYP710A Encodes the Sterol C-22 Desaturase in Arabidopsis and Tomato[W][OA
?22-Unsaturated sterols, containing a double bond at the C-22 position in the side chain, occur specifically in fungi and plants. Here, we describe the identification and characterization of cytochrome P450s belonging to the CYP710A family as the plant C-22 desaturase. Recombinant proteins of CYP710A1 and CYP710A2 from Arabidopsis thaliana and CYP710A11 from tomato (Lycopersicon esculentum) were expressed using a baculovirus/insect system. The Arabidopsis CYP710A1 and tomato CYP710A11 proteins exhibited C-22 desaturase activity with ?-sitosterol to produce stigmasterol (CYP710A1, Km = 1.0 ?M and kinetic constant [kcat] = 0.53 min?1; CYP710A11, Km = 3.7 ?M and kcat = 10 min?1). In Arabidopsis transgenic lines with CYP710A1 and CYP710A11 overexpression, stigmasterol levels increased by 6- to 32-fold. Arabidopsis CYP710A2 was able to produce brassicasterol and stigmasterol from 24-epi-campesterol and ?-sitosterol, respectively. Sterol profiling analyses for CYP710A2 overexpression and a T-DNA insertion event into CYP710A2 clearly demonstrated in planta that CYP710A2 was responsible for both brassicasterol and stigmasterol production. Semiquantitative PCR analyses and promoter:?-glucuronidase transgenic approaches indicated strict tissue/organ-specific regulation for each CYP710A gene, implicating differential tissue distributions of the ?22-unsaturated sterols in Arabidopsis. Our results support the possibility that the CYP710 family may encode P450s of sterol C-22 desaturases in different organisms.
Morikawa, Tomomi; Mizutani, Masaharu; Aoki, Nozomu; Watanabe, Bunta; Saga, Hirohisa; Saito, Shigeki; Oikawa, Akira; Suzuki, Hideyuki; Sakurai, Nozomu; Shibata, Daisuke; Wadano, Akira; Sakata, Kanzo; Ohta, Daisaku
Cecropin A-derived peptides are potent inhibitors of fungal plant pathogens.
Cecropins are naturally occurring peptides that play an important role in the immune response of insects. Cecropin A-derived and cecropin A-melittin hybrid peptides, all smaller than the natural compound cecropin A, were synthesized and tested for their ability to inhibit growth of several agronomically important fungal pathogens. We found that an 11-amino-acid sequence, corresponding to the N-terminal amphipathic alpha-helix domain of cecropin A, exhibited antifungal activity. Differences in susceptibility of the various pathogens were observed, Phytophthora infestans being particularly sensitive to the shortened cecropin A peptides (IC50 = 2 x 10(-6) M). Biotoxicity of the shortest cecropin A-derived peptide was variously affected by the presence of proteins extracted from leaves of tobacco and tomato plants, either total extracts or intercellular fluids (ICFs). Overall, there was a greater tolerance to tomato protein extracts than to tobacco extracts. These findings suggest that tobacco should not be used as a model for testing the possible protective effects of transgenically expressed, cecropin-based genes. The feasibility of tailoring cecropin A genes to enhance crop protection in particular plant/fungus combinations is discussed. PMID:9487696
Cavallarin, L; Andreu, D; San Segundo, B
Practical synthesis of natural plant-growth regulator 2-azahypoxanthine, its derivatives, and biotin-labeled probes.
We describe a practical, large-scale synthesis of the "fairy-ring" plant-growth regulator 2-azahypoxanthine (AHX), and its biologically active hydroxyl metabolite (AOH) and riboside derivative (AHXr). AHXr, a biosynthetic intermediate, was synthesized from inosine via a biomimetic route. Biotinylated derivatives of AHX and AHXr were also synthesized as probes for mechanistic studies. PMID:24802664
Ikeuchi, Kazutada; Fujii, Ryosuke; Sugiyama, Shimpei; Asakawa, Tomohiro; Inai, Makoto; Hamashima, Yoshitaka; Choi, Jae-Hoon; Suzuki, Tomohiro; Kawagishi, Hirokazu; Kan, Toshiyuki
Bioefficacy of some plant derivatives that protect grain against the pulse beetle, Callosobruchus maculatus.
Experiments were conducted to study the bioefficacies of different plant/weed derivatives that affect the development of the pulse beetle, Callosobruchus maculates F. (Coleoptera: Bruchidae) fed on black gram, Vigna mungo, seeds. Plant extracts, powder, ash and oil from nishinda (Vitex negundo L.), eucalyptus (Eucalyptus globules Labill.), bankalmi (Ipomoea sepiaria K.), neem (Azadirachta indica L.), safflower (Carthamus tinctorius L.), sesame (Sesamum indicum L.) and bablah (Acacia arabica L.) were evaluated for their oviposition inhibition, surface protectant, residual toxicity and direct toxicity effects on C. maculates. The results showed that plant oils were effective in checking insect infestation. The least number of F(1) adults emerged from black gram seeds treated with neem oil. The nishinda oil extract was the most toxic of three extracts tested (nishinda, eucalyptus and bankalmi). Bablah ash was the most effective compared to the powdered leaves of nishinda, eucalyptus and bankalmi. The powdered leaves and extracts of nishinda, eucalyptus and bankalmi, at a 3% mixture, provided good protection for black gram seeds by reducing insect oviposition, F(1) adult emergence, and grain infestation rates. The oil treatment did not show adverse effects on germination capability of seeds, even after three months of treatment. PMID:19537990
Rahman, A; Talukder, F A
Depletion of phytosterols from the plant plasma membrane provides evidence for disruption of lipid rafts
Involvement of sterols in membrane structural properties has been extensively studied in model systems but rarely assessed in natural mem- branes and never investigated for the plant plasma membrane (PM). Here, we address the question of the role of phytosterols in the organization of the plant PM. The sterol composition of tobacco BY-2 cell PM was determined by gas chromatography.
Yann Roche; Patricia Gerbeau-Pissot; Blandine Buhot; Dominique Thomas; Laurent Bonneau; Joseph Gresti; Sebastien Mongrand; Jean-Marie Perrier-Cornet; Francoise Simon-Plas
Large-scale Gene Ontology analysis of plant transcriptome-derived sequences retrieved by AFLP technology
Background After 10-year-use of AFLP (Amplified Fragment Length Polymorphism) technology for DNA fingerprinting and mRNA profiling, large repertories of genome- and transcriptome-derived sequences are available in public databases for model, crop and tree species. AFLP marker systems have been and are being extensively exploited for genome scanning and gene mapping, as well as cDNA-AFLP for transcriptome profiling and differentially expressed gene cloning. The evaluation, annotation and classification of genomic markers and expressed transcripts would be of great utility for both functional genomics and systems biology research in plants. This may be achieved by means of the Gene Ontology (GO), consisting in three structured vocabularies (i.e. ontologies) describing genes, transcripts and proteins of any organism in terms of their associated cellular component, biological process and molecular function in a species-independent manner. In this paper, the functional annotation of about 8,000 AFLP-derived ESTs retrieved in the NCBI databases was carried out by using GO terminology. Results Descriptive statistics on the type, size and nature of gene sequences obtained by means of AFLP technology were calculated. The gene products associated with mRNA transcripts were then classified according to the three main GO vocabularies. A comparison of the functional content of cDNA-AFLP records was also performed by splitting the sequence dataset into monocots and dicots and by comparing them to all annotated ESTs of Arabidopsis and rice, respectively. On the whole, the statistical parameters adopted for the in silico AFLP-derived transcriptome-anchored sequence analysis proved to be critical for obtaining reliable GO results. Such an exhaustive annotation may offer a suitable platform for functional genomics, particularly useful in non-model species. Conclusion Reliable GO annotations of AFLP-derived sequences can be gathered through the optimization of the experimental steps and the statistical parameters adopted. The Blast2GO software was shown to represent a comprehensive bioinformatics solution for an annotation-based functional analysis. According to the whole set of GO annotations, the AFLP technology generates thorough information for angiosperm gene products and shares common features across angiosperm species and families. The utility of this technology for structural and functional genomics in plants can be implemented by serial annotation analyses of genome-anchored fragments and organ/tissue-specific repertories of transcriptome-derived fragments.
Botton, Alessandro; Galla, Giulio; Conesa, Ana; Bachem, Christian; Ramina, Angelo; Barcaccia, Gianni
Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity1234
Background: The rise in LDL with egg feeding in lean insulin-sensitive (LIS) participants is 2- and 3-fold greater than in lean insulin-resistant (LIR) and obese insulin-resistant (OIR) participants, respectively. Objective: We determined whether differences in cholesterol absorption, synthesis, or both could be responsible for these differences by measuring plasma sterols as indexes of cholesterol absorption and endogenous synthesis. Design: Plasma sterols were measured by gas chromatography–mass spectrometry in a random subset of 34 LIS, 37 LIR, and 37 OIR participants defined by the insulin sensitivity index (SI) and by BMI criteria selected from a parent group of 197 participants. Cholestanol and plant sterols provide a measure of cholesterol absorption, and lathosterol provides a measure of cholesterol synthesis. Results: The mean (±SD) ratio of plasma total absorption biomarker sterols to cholesterol was 4.48 ± 1.74 in LIS, 3.25 ± 1.06 in LIR, and 2.82 ± 1.08 in OIR participants. After adjustment for age and sex, the relations of the absorption sterol–cholesterol ratios were as follows: LIS > OIR (P < 0.001), LIS > LIR (P < 0.001), and LIR > OIR (P = 0.11). Lathosterol-cholesterol ratios were 0.71 ± 0.32 in the LIS participants, 0.95 ± 0.47 in the LIR participants, and 1.29 ± 0.55 in the OIR participants. After adjustment for age and sex, the relations of lathosterol-cholesterol ratios were as follows: LIS < OIR (P < 0.001), LIS < LIR (P = 0.03), and LIR < OIR (P = 0.002). Total sterol concentrations were positively associated with SI and negatively associated with obesity, whereas lathosterol correlations were the opposite. Conclusions: Cholesterol absorption was highest in the LIS participants, whereas cholesterol synthesis was highest in the LIR and OIR participants. Therapeutic diets for hyperlipidemia should emphasize low-cholesterol diets in LIS persons and weight loss to improve SI and to decrease cholesterol overproduction in LIR and OIR persons.
Knopp, Robert H; Kahn, Steven E; Retzlaff, Barbara M; Fish, Brian; Ma, Lina; Ostlund, Richard E
Impact of botanical pesticides derived from Melia azedarach and Azadirachta indica plants on the emission of volatiles that attract Parasitoids of the diamondback moth to cabbage plants.
Herbivorous and carnivorous arthropods use chemical information from plants during foraging. Aqueous leaf extracts from the syringa tree Melia azedarach and commercial formulations from the neem tree Azadirachta indica, Neemix 4.5, were investigated for their impact on the flight response of two parasitoids, Cotesia plutellae and Diadromus collaris. Cotesia plutellae was attracted only to Plutella xylostella-infested cabbage plants in a wind tunnel after an oviposition experience. Female C. plutellae did not distinguish between P. xylostella-infested cabbage plants treated with neem and control P. xylostella-infested plants. However, females preferred infested cabbage plants that had been treated with syringa extract to control infested plants. Syringa extract on filter paper did not attract C. plutellae. This suggests that an interaction between the plant and the syringa extract enhances parasitoid attraction. Diadromus collaris was not attracted to cabbage plants in a wind tunnel and did not distinguish between caterpillar-damaged and undamaged cabbage plants. Headspace analysis revealed 49 compounds in both control cabbage plants and cabbage plants that had been treated with the syringa extract. Among these are alcohols, aldehydes, ketones, esters, terpenoids, sulfides, and an isothiocyanate. Cabbage plants that had been treated with the syringa extract emitted larger quantities of volatiles, and these increased quantities were not derived from the syringa extract. Therefore, the syringa extract seemed to induce the emission of cabbage volatiles. To our knowledge, this is the first example of a plant extract inducing the emission of plant volatiles in another plant. This interesting phenomenon likely explains the preference of C. plutellae parasitoids for cabbage plants that have been treated with syringa extracts. PMID:16555134
Charleston, Deidre S; Gols, Rieta; Hordijk, Kees A; Kfir, Rami; Vet, Louise E M; Dicke, Marcel
NSDL National Science Digital Library
Murray Bourne developed the Interactive Mathematics site while working as a mathematics lecturer at Ngee Ann Polytechnic in Singapore. The site contains numerous mathematics tutorials and resources for students and teachers alike. This specific page is focused on differentiation, or finding derivatives. Bourne walks users through an introduction to differentiation and limits, and then moves on to more specific applications like rate of change, derivatives of polynomials, and differentiating powers of a function. Each topic includes graphs and interactive materials designed to aid users in understanding the presented concepts. The information here is presented in a clear, straightforward manner that is appropriate for introductory and advanced calculus students alike.
Bourne, Murray
NSDL National Science Digital Library
In this activity, students input functions in order to calculate the derivative and tangent line of that function. This activity allows students to explore tangent lines of various functions. This activity includes supplemental materials, including background information about the topics covered, a description of how to use the application, and exploration questions for use with the java applet.
Modification of the sterol composition of Trypanosoma (Schizotrypanum) cruzi epimastigotes by delta 24(25)-sterol methyl transferase inhibitors and their combinations with ketoconazole.
We report a detailed analysis of the sterol composition of Trypanosoma cruzi epimastigotes grown in the absence or presence of two sterol analogs previously reported as inhibitors of delta 24(25) sterol methyltransferase (24(25)-SMT,E.C.220.127.116.11) in yeast and fungi, a cholestanol analog with a 6-membered aza ring as side chain (22,26-azasterol) and 24-(R,S),25-epiminolanosterol, as well as combinations of these compounds with the C14 demethylase inhibitor ketoconazole. Both sterol analogs produced a dose-dependent reduction in the incorporation of radioactivity from [methyl-14C]methionine with IC50 values of 640 nM and 70 nM for 22,26-azasterol and 24,25-(R,S)-epiminolanosterol, respectively, indicating a specific inhibition of 24(25)-SMT. Correspondingly, it was found that the sterols present in control cells (ergosterol, 24-ethylcholesta-5,7,22-trien-3 beta-ol and precursors) were almost completely replaced by zymosterol (cholesta-8,24-dien-3 beta-ol) or a mixture of zymosterol, cholesta-7,24-dien-3 beta-ol and cholesta-5,7,24-trien-3 beta-ol when the parasites were exposed to the minimal growth inhibitory concentrations of 22,26-azasterol and 24-(R,S),25-epiminolanosterol, respectively. At sub-optimal concentrations of the inhibitors a complete disappearance of the 24-ethyl sterols was observed and a concomitant increase in the proportion of 24-methyl sterols, particularly delta 24(24') sterols. This showed that in T. cruzi the second methenylation step (catalyzed by delta 24(24') sterol methyl transferase) was significantly more sensitive to these inhibitors than the first and that the sterol analogs were also powerful inhibitors of the delta 24(24') sterol reductase. In growth-arrested epimastigotes resulting from their treatment with low (1-3 microM) concentrations of either sterol analog combined with sub optimal (100-300 nM) levels of ketoconazole the main sterol was lanosterol with no evidence 24-methylenedihydrolanosterol, the main sterol found in cells treated with growth inhibitory concentrations of the azole alone. Taken together, these results indicated that 24-alkyl sterols are essential growth factors for T. cruzi and that the preferred substrate of the delta 24(25) sterol methyl transferase in this organism is zymosterol. PMID:8577328
Urbina, J A; Vivas, J; Visbal, G; Contreras, L M
Model-derived dose rates per unit concentration of radon in air in a generic plant geometry.
A model for the derivation of dose rates per unit radon concentration in plants was developed in line with the activities of a Task Group of the International Commission on Radiological Protection (ICRP), aimed at developing more realistic dosimetry for non-human biota. The model considers interception of the unattached and attached fractions of the airborne radon daughters by plant stomata, diffusion of radon gas through stomata, permeation through the plant's epidermis and translocation of deposited activity to plant interior. The endpoint of the model is the derivation of dose conversion coefficients relative to radon gas concentration at ground level. The model predicts that the main contributor to dose is deposition of (214)Po ?-activity on the plant surface and that diffusion of radon daughters through the stomata is of relatively minor importance; hence, daily variations have a small effect on total dose. PMID:21739195
Vives i Batlle, J; Smith, A; Vives-Lynch, S; Copplestone, D; Pröhl, G; Strand, T
Genetic biomarkers of the sterol-biosynthetic pathway in microalgae.
Sterols are cyclic isoprenoid lipids present in all eukaryotes. These compounds have been used to determine the composition of algal communities in marine and lake environments, and because of their preservation potential have been used to reconstruct the evolution of eukaryotes. In the last years, there have been major advances in understanding the sterol biosynthetic pathways and the enzymes involved. Here, we have explored the diversity and phylogenetic distribution of the gene coding the cycloartenol synthase (CS), a key enzyme of the phytosterol biosynthetic pathway. We propose a gene-based approach that can be used to assess the sterol-forming potential of algal groups. CS coding gene was annotated in genomes of microalgae using protein homology with previously annotated CS sequences. Primers for the detection of CS gene sequences of diatoms, one of the most dominant groups of microalgae, were designed and evaluated in cultures and environmental samples. A comparison of the phylogeny of the recovered CS sequences in combination with sequence data of the gene rbcL coding for the large subunit of the ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) demonstrates the potential of the CS gene as phylogenetic marker, as well as an indicator for the identity of sterol-producing organisms in the environment. PMID:24596261
Villanueva, Laura; Rijpstra, W Irene C; Schouten, Stefan; Damsté, Jaap S Sinninghe
The genetics and molecular genetics of terpene and sterol origami
Terpenes and sterols are complex molecules synthesized by equally complex biosynthetic pathways. Recent progress in using the tools of genetics, molecular genetics and genetic engineering to dissect triterpene metabolism in the cytosol, and terpene metabolism in the plastids, has opened up new strategies and avenues of investigation. Most importantly, these studies have enhanced our appreciation of the biological significance of
Joe Chappell
Methodological considerations for the harmonization of non-cholesterol sterol bio-analysis.
Non-cholesterol sterols (NCS) are used as surrogate markers of cholesterol metabolism which can be measured from a single blood sample. Cholesterol precursors are used as markers of endogenous cholesterol synthesis and plant sterols are used as markers of cholesterol absorption. However, most aspects of NCS analysis show wide variability among researchers within the area of biomedical research. This variability in methodology is a significant contributor to variation between reported NCS values and hampers the confidence in comparing NCS values across different research groups, as well as the ability to conduct meta-analyses. This paper summarizes the considerations and conclusions of a workshop where academic and industrial experts met to discuss NCS measurement. Highlighted is why each step in the analysis of NCS merits critical consideration, with the hopes of moving toward more standardized and comparable NCS analysis methodologies. Alkaline hydrolysis and liquid-liquid extraction of NCS followed by parallel detection on GC-FID and GC-MS is proposed as an ideal methodology for the bio-analysis of NCS. Furthermore the importance of cross-comparison or round robin testing between various groups who measure NCS is critical to the standardization of NCS measurement. PMID:24674990
Mackay, Dylan S; Jones, Peter J H; Myrie, Semone B; Plat, Jogchum; Lütjohann, Dieter
Brain sterol dys-regulation in sporadic AD and MCI: Relationship to heme oxygenase-1
The objective of this study was to ascertain the impact of aging and Alzheimer disease (AD) on brain cholesterol (CH), CH precursors and oxysterol homeostasis. Altered CH metabolism and up-regulation of heme oxygenase-1 (HO-1) are characteristic of AD-affected neural tissues. We recently determined that HO-1 over-expression suppresses total CH levels by augmenting liver X receptor-mediated CH efflux and enhances oxysterol formation in cultured astroglia. Lipids and proteins were extracted from post-mortem human frontal cortex derived from subjects with sporadic AD, mild cognitive impairment (MCI) and no cognitive impairment (NCI; n=17 per group) enrolled in the Religious Orders Study, an ongoing clinical-pathologic study of aging and AD. ELISA was used to quantify human HO-1 protein expression from brain tissue and GC-MS to quantify total CH, CH precursors and relevant oxysterols. The relationships of sterol/oxysterol levels to HO-1 protein expression and clinical/demographic variables were determined by multivariable regression and non-parametric statistical analyses. Decreased CH, increased oxysterol and increased CH precursors concentrations in the cortex correlated significantly with HO-1 levels in MCI and AD, but not NCI. Specific oxysterols correlated with disease state, increasing neuropathological burden, neuropsychological impairment and age. A model featuring compensated and de-compensated states of altered sterol homeostasis in MCI and AD are presented based on the current data set and our earlier in vitro work.
Hascalovici, Jacob R.; Vaya, Jacob; Khatib, Soliman; Holcroft, Christina A.; Zukor, Hillel; Song, Wei; Arvanitakis, Zoe; Bennett, David A.; Schipper, Hyman M.
Sterol composition of Cryptococcus neoformans in the presence and absence of fluconazole.
Analysis of the sterol compositions of 13 clinical isolates of the pathogenic yeast Cryptococcus neoformans obtained from five patients with recurring cryptococcal meningitis showed that, unlike Candida albicans, the major sterols synthesized by this yeast were obtusifoliol (range, 21.1 to 68.2%) and ergosterol (range, 0.0 to 46.5%). There was considerable variation in the sterol contents among the 13 isolates, with total sterol contents ranging from 0.31 to 5.9% of dry weight. The isolates from the five patients who had relapses had different total sterol contents and compositions in comparison with those of the pretreatment isolates, indicating either that the sterols had been changed by therapy or that the patients were infected with new isolates with different sterol compositions. Growth of the cryptococcal isolates in the presence of subinhibitory concentrations of fluconazole (0.25x the MIC) significantly altered the sterol content and pattern. The total sterol content decreased in nine isolates and increased in four isolates in response to pretreatment with fluconazole. Fluconazole had no consistent effect on ergosterol levels. In contrast, fluconazole caused a decrease in obtusifoliol levels and an increase in 4,14-dimethylzymosterol levels in all isolates. These results indicate extensive diversity in sterol content, sterol composition, and sterol synthesis in response to subinhibitory concentrations of fluconazole in C. neoformans strains. We propose that fluconazole inhibits the sterol synthesis of C. neoformans by interfering with both 14 alpha-demethylase-dependent and -independent pathways. No correlation between the sterol compositions of C. neoformans isolates and their susceptibilities to fluconazole was found.
Ghannoum, M A; Spellberg, B J; Ibrahim, A S; Ritchie, J A; Currie, B; Spitzer, E D; Edwards, J E; Casadevall, A
Invasive plant-derived biochar inhibits sulfamethazine uptake by lettuce in soil.
Veterinary antibiotics are frequently detected in soils posing potential contamination of food crops. Sulfamethazine (SMT) uptake was investigated by lettuce (Lactuca sativa L.) grown in the soils treated with/without biochar derived from an invasive plant, burcucumber (Sicyos angulatus L.) (BBC700). Soils were contaminated with SMT at 5 and 50mgkg(-1), and treated with/without 5% BBC700 (ww(-1)). The lettuces were harvested after 5weeks of cultivation and were analyzed for SMT by a high performance liquid chromatography-tandem mass spectrometry after solid-phase extraction. With 5% BBC700, the uptake of SMT was reduced by 86% in the soil spiked with 5mgkg(-1) SMT compared to the control whereas a 63% reduction was observed in the soil spiked with 50mgkg(-1) SMT. Application of BBC700, into soils effectively reduced the SMT uptake by lettuce. PMID:24997958
Rajapaksha, Anushka Upamali; Vithanage, Meththika; Lim, Jung Eun; Ahmed, Mohamed Bedair M; Zhang, Ming; Lee, Sang Soo; Ok, Yong Sik
Inhibition of Naja naja venom hyaluronidase by plant-derived bioactive components and polysaccharides.
The inhibitory effect of several bioactive compounds on the activity of hyaluronidase enzyme purified from Naja naja venom was investigated in vitro. Compounds were found to inhibit the hyaluronidase activity dose dependently. Among glycosaminoglycans, heparin, heparan sulfate, and dermatan sulfate showed maximum inhibition compared to chondroitin sulfates. Different molecular forms of chitosan inhibit the enzyme, and inhibition appears to depend on the chain length. In addition, plant-derived bioactive compounds also inhibited the activity of hyaluronidase dose dependently. Among those tested, aristolochic acid, indomethacin, quercetin, curcumin, tannic acid, and flavone exhibited inhibition, with aristolochic acid and quercetin completely inhibiting the enzyme activity. It is concluded that the inhibitors of hyaluronidase could be used as potent first aid agents in snakebite therapy. Furthermore, these inhibitors not only reduce the local tissue damage but also retard the easy diffusion of systemic toxins and hence increase survival time. PMID:16212553
Girish, K S; Kemparaju, K
Effects of dietary administration of plant-derived anthocyanin-rich colors to spontaneously hypertensive rats.
Anthocyanins have beneficial effects such as free radical scavenging activity. We investigated the effects of continuous administration of colors from purple corn (PCC), purple sweet potato (PSC) and red radish (RRC) to spontaneously hypertensive rats (SHR). These are rich in anthocyanins. Animals were fed with diets containing PCC, PSC or RRC (1 mass% of diets) for 15 wk. While the body weight and the daily food intake of administered rats were not different from those of the non-administered control rats through the experimental period, the blood pressure and the heart rate of SHR administered each color decreased as compared to the control group from the early stage of administration. These results suggest that plant-derived colors containing anthocyanins have anti-hypertensive effects on hypertensive animals. PMID:17484387
Shindo, Makoto; Kasai, Toshikazu; Abe, Asaki; Kondo, Yasuhiro
Deriving a Planting Medium from Solid Waste Compost and Construction, Demolition and Excavation Waste
NASA Astrophysics Data System (ADS)
Lebanon's very high population density has been increasing since the end of the war in the early 1990s reaching 416.36 people per square kilometer. Furthermore, the influx of refugees from conflicts in the region has increased the resident population significantly. All these are exerting pressure on the country's natural resources, pushing the Lebanese to convert more forest and agricultural land into roads, buildings and houses. This has led to a building boom and rapid urbanization which in turn has created a demand for construction material - mainly rock, gravel, sand, etc. nearly all of which were locally acquired through quarrying to the tune of three million cubic meters annually. This boom has been followed by a war with Israel in 2006 which resulted in thousands of tonnes of debris. The increase in population has also led to an increase in solid waste generation with 1.57 million tonnes of solid waste generated in Lebanon per year. The combination of construction, demolition and excavation (CDE) waste along with the increase in solid waste generation has put a major stress on the country and on the management of its solid waste problem. Compounding this problem are the issues of quarries closure and rehabilitation and a decrease in forest and vegetative cover. The on-going research reported in this paper aims to provide an integrated solution to the stated problem by developing a "soil mix" derived from a mélange of the organic matter of the solid waste (compost), the CDE waste, and soil. In this mix, native and indicator plants are planted (in pots) from which the most productive mix will be selected for further testing at field level in later experiments. The plant species used are Matiolla, a native Lebanese plant and Zea mays, which is commonly known used as an indicator plant due to its sensitivity to environmental conditions. To ensure sustainability and environmental friendliness of the mix, its physical and chemical characteristics are monitored and assessed. The leachate from the irrigation of the pots is also monitored and assessed to ensure that if selected for field trials, the mix will not pose a threat to water bodies. The presentation at the conference will aim to report the latest results from the on-going experiment.
Farajalla, Nadim; Assaf, Eleni; Bashour, Issam; Talhouk, Salma
Effect of Plant-derived Hydrophobic Compounds on Soil Water Repellency in Dutch Sandy Soils
NASA Astrophysics Data System (ADS)
Soil water repellency or hydrophobicity is a common and important soil property, which may diminish plant growth and promotes soil erosion leading to environmentally undesired situations. Hydrophobic organic compounds in the soil are derived from vegetation (leaves, roots, mosses) or microorganisms (fungi, bacteria), and these compounds induce soil water repellency (SWR) and can be called SWR-biomarkers. As common hydrophobic constituents of organic matter, plant lipids are mainly from wax layers of leaves and roots, whereas cutins and suberins as aliphatic biopolyesters occur in leaves and roots, respectively. Their unique compositions in soil can indicate the original vegetation sources. To investigate the individual or combined effects of the hydrophobic compounds on SWR and their possible associations with each other, we conducted experiments to analyse the organic composition of Dutch coastal dune sandy soils in relation to SWR. DCM/MeOH solvent is used to remove solvent soluble lipids. BF3-methanol is utilized to depolymerize cutins and suberins from isopropanol/NH3 extractable organic matter. Total organic carbon (TOC) has a positive linear relation with SWR only for those soils containing low TOC (
Mao, Jiefei; Dekker, Stefan C.; Nierop, Klaas G. J.
Synthesis of Biginelli dihydropyrimidinone derivatives with various substituents on aluminium-planted mesoporous silica catalyst.
Biginelli reactions were well catalyzed on mesoporous silica MCM-41 (M41) whose activity was much greater than that of amorphous silica. Octane was the most suitable among 6 kinds of solvents examined. The addition of metal ions on M41 enhanced the catalytic activity in the order Al > Ti > Fe = In. Al-planted M41s with Si/Al ratios of 45-35 showed the highest catalytic activity and could be used repeatedly though a small loss of the activity was observed. The catalysis could widely be applied to obtain various substituted dihydropyrimidinones (DHPMs) with high yields, some of which were very difficult to prepare until now. In addition, Biginelli reactions were combined with formyl C-H insertion reactions of diazoester on mesoporous silica; that is, a tandem one-pot four-component DHPM synthesis was attempted. Acetaldehyde, ethyl diazoacetate, p-tolualdehyde, and urea could be condensed and the corresponding DHPM derivative was obtained with 50% yield on Al-planted M41. PMID:20165814
Murata, Hiroaki; Ishitani, Haruro; Iwamoto, Masakazu
Fate of octyl- and nonylphenol ethoxylates and some carboxylated derivatives in three american wastewater treatment plants.
The fate of a comprehensive group of nonylphenol and octylphenol ethoxylates (APEOs) and several of their carboxylated derivatives was studied in three American wastewatertreatment plants (WWTPs), two of which included advanced treatment. Influent and effluent concentrations of the alkylphenolic compounds (APEs) in the three plants were very similar, but effluent concentrations showed a seasonal dependency: both carboxylate and ethoxylate concentrations in the effluents were higher in winter than in summer. Sorption to particulate matter was higher for nonylphenolic compounds than for their octylphenolic counterparts, in agreement with their difference in Kow values. Both effluent concentrations and the removal efficiency of the APEOs were strongly correlated to water temperature, but no correlation was found with suspended solids or organic carbon removal. Although APEO removal from wastewater was high, overall removal from the WWTPs, including APEOs in waste sludge and transformation products, was relatively low and suggested that advanced treatment does not invariably result in better APEO removal. Additionally, a survey of urban sewers suggested that household products still constitute an important source of the APEOs reaching WWTPs. PMID:17969700
Loyo-Rosales, Jorge E; Rice, Clifford P; Torrents, Alba
Microbial and plant derived biomass for removal of heavy metals from wastewater.
Discharge of heavy metals from metal processing industries is known to have adverse effects on the environment. Conventional treatment technologies for removal of heavy metals from aqueous solution are not economical and generate huge quantity of toxic chemical sludge. Biosorption of heavy metals by metabolically inactive non-living biomass of microbial or plant origin is an innovative and alternative technology for removal of these pollutants from aqueous solution. Due to unique chemical composition biomass sequesters metal ions by forming metal complexes from solution and obviates the necessity to maintain special growth-supporting conditions. Biomass of Aspergillus niger, Penicillium chrysogenum, Rhizopus nigricans, Ascophyllum nodosum, Sargassum natans, Chlorella fusca, Oscillatoria anguistissima, Bacillus firmus and Streptomyces sp. have highest metal adsorption capacities ranging from 5 to 641 mg g(-1) mainly for Pb, Zn, Cd, Cr, Cu and Ni. Biomass generated as a by-product of fermentative processes offers great potential for adopting an economical metal-recovery system. The purpose of this paper is to review the available information on various attributes of utilization of microbial and plant derived biomass and explores the possibility of exploiting them for heavy metal remediation. PMID:16427277
Ahluwalia, Sarabjeet Singh; Goyal, Dinesh
More good news about polymeric plant- and algae-derived biomaterials in drug delivery systems.
Natural polymers are continuously investigated for use in pharmaceutical and tissue engineering applications due to the renewability of their supply. Besides the conventional use of natural materials in dosage form design such as fillers, they are progressively investigated as functional excipients in specialised dosage forms. The hydrophilic nature of natural polymers together with their non-toxic and biodegradable properties make them useful in the design of modified release dosage forms. Matrix type tablets and beads made from natural gums and mucilages often exhibit sustained drug release through erosion in combination with swelling. Natural polymers are used to reach different pharmaceutical objectives, for instance, inulin and pectin are plant derived polymers that have suitable properties to produce colon-specific drug delivery. Alginate is an example of a natural polymer that has been used in the formulation of gastro-retentive dosage forms. Different cellulose derived polymers have been investigated as coating materials for dosage forms. Natural polymers can be chemically modified to produce molecules with specific properties and formation of co-polymers or polymer mixtures provide new opportunities to develop innovative drug delivery systems. PMID:24597532
Scholtz, Jacques; Van der Colff, Jaco; Steenekamp, Jan; Stieger, Nicole; Hamman, Josias
The effect of variations in phospholipid and sterol structure on the nature of lipid-sterol interactions in lipid bilayer model membranes.
This review deals with the effect of variations in phospholipid and sterol structure on the nature and magnitude of lipid-sterol interactions in lipid bilayer model membranes. The first portion of the review covers the effect of Chol itself on the thermotropic phase behavior and organization of a variety of different glycero- and sphingolipid membrane lipid classes, varying in the structure and charge of their polar headgroups and in the length and structure of their fatty acyl chains. The second part of this review deals with the effect of variations in sterol structure on the thermotropic phase behavior and organization primarily of the well studied DPPC model membrane system. In the third section, we focus on some of the contributions of sterol functional group chemistry, molecular conformation and dynamics, to sterol-lipid interactions. Using those studies, we re-examine the results of recently published experimental and computer-modeling studies to provide a new more dynamic molecular interpretation of sterol-lipid interactions. We suggest that the established view of the rigid sterol ring system and extended alkyl side-chain obtained from physical studies of cholesterol-phospholipid mixtures may not apply in lipid mixtures differing in their sterol chemical structure. PMID:20371224
Mannock, David A; Lewis, Ruthven N A H; McMullen, Todd P W; McElhaney, Ronald N
A trial of production of the plant-derived high-value protein in a plant factory
One of the ultimate goals of plant science is to test a hypothesis obtained by basic science and to apply it to agriculture and industry. A plant factory is one of the ideal systems for this trial. Environmental factors affect both plant yield and the accumulation of recombinant proteins for industrial applications within transgenic plants. However, there have been few reports studying plant productivity for recombinant protein in closed cultivation systems called plant factories. To investigate the effects of photosynthetic photon flux (PPF) on tomato fruit yield and the accumulation of recombinant miraculin, a taste-modifying glycoprotein, in transgenic tomato fruits, plants were cultivated at various PPFs from 100 to 400 (µmol m?2 s?1) in a plant factory. Miraculin production per unit of energy used was highest at PPF100, although miraculin production per unit area was highest at PPF300. The commercial productivity of recombinant miraculin in transgenic tomato fruits largely depended on light conditions in the plant factory. Our trial will be useful to consider the trade-offs between the profits from production of high-value materials in plants and the costs of electricity.
Hirai, Tadayoshi; Hiwasa-Tanase, Kyoko; Goto, Eiji
Evaluation of the anti-Listeria potentials of some plant-derived triterpenes
Background Listeriosis is a fatal disease caused by pathogenic Listeria bacteria and it is most prevalent in immune-compromised individuals. The increase in numbers of immune-compromised individuals against a background of Listeria antibiotic resistance, limits listeriosis treatment options. This therefore calls for research into substitute treatments, of which, medicinal plants derived compounds offer a viable alternative. Methods The broth microdilution assay was used to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of three plant triterpenes namely 3?-hydroxylanosta-9,24-dien-21-oic acid, methyl-3?-hydroxylanosta-9,24-dien-21-oate and 3?-acetylursolic acid, against Listeria monocytogenes, Listeria ivanovii and Listeria grayi species. The chequerboard method was used to assess the interactions between the triterpenes and conventional antibiotics: ampicillin, neomycin, gentamicin and penicillin G. The lactate dehydrogenase membrane damage method was used to assess the triterpenes' membrane damaging potentials against the Listeria bacteria. Results The triterpenes' MIC values were found to range from 0.185 to 1.67 mg/ml while, the MBC determination assay results revealed that the test triterpenes were bacteriostatic against the Listeria bacteria. The interactions involving 3?-hydroxylanosta-9,24-dien-21-oic acid were mainly additive with ampicillin and synergistic with neomycin, gentamicin and penicillin G. The interactions involving methyl-3?-hydroxylanosta-9,24-dien-21-oate were mainly antagonistic with ampicillin, indifferent with neomycin, ranging from synergistic to indifference with gentamicin and synergistic with penicillin G. The interactions involving 3?-acetylursolic acid were mainly indifferent with ampicillin, synergistic with neomycin and gentamicin while ranging between synergistic and additive with penicillin G. The low levels of cytosolic lactate dehydrogenase released from the cells treated with 4× MIC concentration of the triterpenes in comparison to that of cells treated with 3% Triton X-100 proved that membrane damage was not the mode of action of the triterpenes. Conclusion This study therefore shows the potential that these plant triterpenes have in listeriosis chemotherapy especially as shown by the favourable interactions they had with penicillin G, one of the antibiotics of choice in listeriosis treatment.
[Microbial models in screening of inhibitors of sterol biosynthesis].
On the base of previously developed microbial models high effective scheme for screening of inhibitors of sterol biosynthesis (ISB) is proposed. It is based on cultivation of halophilic bacteria Halobacterium salinarum (former Halobacterium halobium), possessing mevalonate pathway of sterol biosynthesis, and cultivation of fungus Acremonium fusidioides (former Fusidium coccineum), that is producer of steroid antibiotic fusidin (fusidic acid), which biosynthesis has great similarity (with coincidence of its initial steps till squalene formation) to cholesterol biosynthesis in human organism. In H. salinarum model ISB are revealed as compounds that inhibit test-culture growth, whereas in A. fusidioides test-system they are revealed as compounds that strongly reduce fusidin production without any visible influence on producer's growth. Mevalonate that is one of the crucial intermediates of sterol biosynthesis remove inhibition induced by many microbial metabolites that is the evidence of their action at early stages of sterol biosynthetic pathway, including HMG-CoA reductase step. Both test-systems are developed as micromethod and could be easily mechanized due to miniaturization of microbiological procedures, cultivation in sterile 96-well plates and usage of automatic micropipettes and dispensers. Effectiveness of both test-systems, as well as their sensitiveness, laboriousness and ability to give false-positive or false-negative results in ISB screening work is compared. The proposed scheme of screening of ISB includes microbial models at early steps of screening procedures and Hep G2 test-system at the late step. The preliminary screening of microbial metabolites possessing antifungal activity at initial step is compulsory. Miniaturization and mechanization of microbial processes and purification of producers' culture broth with micro- and ultrafiltration are under consideration as well. PMID:24757827
Trenin, A S
Dialkylimidazole inhibitors of Trypanosoma cruzi sterol 14?-demethylase as anti-Chagas disease agents.
New dialkylimidazole based sterol 14?-demethylase inhibitors were prepared and tested as potential anti-Trypanosoma cruzi agents. Previous studies had identified compound 2 as the most potent and selective inhibitor against parasite cultures. In addition, animal studies had demonstrated that compound 2 is highly efficacious in the acute model of the disease. However, compound 2 has a high molecular weight and high hydrophobicity, issues addressed here. Systematic modifications were carried out at four positions on the scaffold and several inhibitors were identified which are highly potent (EC50 <1 nM) against T. cruzi in culture. The halogenated derivatives 36j, 36k, and 36p, display excellent activity against T. cruzi amastigotes, with reduced molecular weight and lipophilicity, and exhibit suitable physicochemical properties for an oral drug candidate. PMID:24120539
Suryadevara, Praveen Kumar; Racherla, Kishore Kumar; Olepu, Srinivas; Norcross, Neil R; Tatipaka, Hari Babu; Arif, Jennifer A; Planer, Joseph D; Lepesheva, Galina I; Verlinde, Christophe L M J; Buckner, Frederick S; Gelb, Michael H
Characterization of transgenic plants derived from hairy roots of Hyoscyamus muticus
Mature plants were regenerated via protoplasts fromAgrobacterium rhizogenes-transformed root cultures ofHyoscyamus muticus L., and chemical analyses were performed on 34 individual plants. The regenerated plants showed strong phenotypic differences from clone to clone as well as from the control plants. Polymerase chain reaction studies revealed that the plants exhibiting the strongest phenotypic alterations contained therol (A, B and C) genes,
N. Sevón; B. Dräger; R. Hiltunen; K.-M. Oksman-Caldentey
Novel composition of mitochondrial genomes in Petunia somatic hybrids derived from cytoplasmic male sterile and fertile plants
The mitochondrial genomes of petunia somatic hybrid plants, which were derived from the fusion of male fertile P. hybrida protoplasts with cytoplasmic male sterile P. parodii protoplasts, were analyzed by endonuclease restriction and Southern blot hybridization analyses. We studied sterile and fertile somatic hybrids to address two main questions. First, is there any correlation between the mitochondrial DNA restriction banding
Maury L. Boeshore; Irit Lifshitz; Maureen R. Hanson; Shamay Izhar
Plant-Derived Polysaccharide Supplements Inhibit Dextran Sulfate Sodium-Induced Colitis in the Rat
Several plant-derived polysaccharides have been shown to have anti-inflammatory activity in animal models. Ambrotose complex and Advanced Ambrotose are dietary supplements that include aloe vera gel, arabinogalactan, fucoidan, and rice starch, all of which have shown such activity. This study was designed to evaluate these formulations against dextran sulfate sodium (DSS)-induced colitis in rats and to confirm their short-term safety after 14 days of daily dosing. Rats were dosed daily orally with vehicle, Ambrotose or Advanced Ambrotose. On day six groups of rats received tap water or 5% Dextran Sulfate sodium. Ambrotose and Advanced Ambrotose significantly lowered the disease scores and partially prevented the shortening of colon length. An increase in monocyte count was induced by dextran sulfate sodium and inhibited by Ambrotose and Advanced Ambrotose. There were no observable adverse effects after 14-day daily doses. The mechanism of action of the formulations against DSS-induced colitis may be related to its effect on monocyte count.
Koetzner, Lee; Grover, Gary; Boulet, Jamie
Plant-derived polysaccharide supplements inhibit dextran sulfate sodium-induced colitis in the rat.
Several plant-derived polysaccharides have been shown to have anti-inflammatory activity in animal models. Ambrotose complex and Advanced Ambrotose are dietary supplements that include aloe vera gel, arabinogalactan, fucoidan, and rice starch, all of which have shown such activity. This study was designed to evaluate these formulations against dextran sulfate sodium (DSS)-induced colitis in rats and to confirm their short-term safety after 14 days of daily dosing. Rats were dosed daily orally with vehicle, Ambrotose or Advanced Ambrotose. On day six groups of rats received tap water or 5% Dextran Sulfate sodium. Ambrotose and Advanced Ambrotose significantly lowered the disease scores and partially prevented the shortening of colon length. An increase in monocyte count was induced by dextran sulfate sodium and inhibited by Ambrotose and Advanced Ambrotose. There were no observable adverse effects after 14-day daily doses. The mechanism of action of the formulations against DSS-induced colitis may be related to its effect on monocyte count. PMID:19513840
Koetzner, Lee; Grover, Gary; Boulet, Jamie; Jacoby, Henry I
Metabolism of a plant derived galactose-containing polysaccharide by Bifidobacterium breve UCC2003.
In this study, we describe the functional characterization of the Bifidobacterium breve UCC2003 gal locus, which is dedicated to the utilization of galactan, a plant-derived polysaccharide. Using a combination of molecular approaches we conclude that the galA gene of B. breve UCC2003 encodes a ?-1,4-endogalactanase producing galacto-oligosaccharides, which are specifically internalized by an ABC transport system, encoded by galBCDE, and which are then hydrolysed to galactose moieties by a dedicated intracellular ?-galactosidase, specified by galG. The generated galactose molecules are presumed to be fed into the fructose-6-phosphate phosphoketolase pathway via the Leloir pathway, thereby allowing B. breve UCC2003 to use galactan as its sole carbon and energy source. In addition to these findings we demonstrate that GalR is a LacI-type DNA-binding protein, which not only appears to control transcription of the galCDEGR operon, but also that of the galA gene. PMID:21375716
O'Connell Motherway, Mary; Fitzgerald, Gerald F; van Sinderen, Douwe
Composition of Lipid-derived Polymers from Different Anatomical Regions of Several Plant Species 1
The composition of the aliphatics of the protective cuticular polymers from different anatomical regions from several plant species was determined by combined gas-liquid chromatography and mass spectrometry of the depolymerization products derived from the polymers. The polymer from the aerial parts of Vicia faba showed similar composition; dihydroxypalmitic acid was the major (>85%) component of the cutin covering leaves, petioles, flower petals and stem with smaller amounts of palmitic acid and ?-hydroxy palmitic acid. On the other hand, the chief components of the polymer from the tap root were ?-hydroxy C16:0 and C18:1 acids and/or the corresponding dicarboxylic acids. The positional isomer composition of the dihydroxy C16 acids was shown to be dependent upon anatomical location, developmental stage, and light. Apple cutin from rapidly expanding organs (flower petal and stigma) was shown to contain predominately C16 family acids whereas the C18 family dominated in cutin of slower growing organs (leaf and fruit). The composition of the aliphatic components of cutin found in the seed coats of pea, corn, barley, and lettuce was found to be similar to that of the cuticular polymer of the leaves in each species. Images
Espelie, Karl E.; Dean, Bill B.; Kolattukudy, P. E.
Tetrahydroxystilbene glucoside, a plant-derived cognitive enhancer, promotes hippocampal synaptic plasticity.
Plant or food derived polyphenols have received a great deal of attention due to their biological properties including anti-oxidative effects, neuroprotection and memory enhancement. Here, we investigated the roles of 2,3,5,4'-tetrahydroxystilbene-2-O-?-d-glucoside (TSG), an active component of the rhizome extracted from Polygonum multiflorum, in the regulation of hippocampal synaptic plasticity in normal mice as well as the underlying mechanisms. It was shown that TSG promoted the differentiation of PC12 cells and increased the intracellular calcium level in hippocampal neurons. TSG facilitated high-frequency stimulation (HFS)-induced hippocampal long-term potentiation (LTP) in a bell-shaped manner. The facilitation of LTP induction by TSG required calcium/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinase (ERK) activation. Taken together, our data demonstrate that TSG promotes LTP induction and this effect may contribute to the enhancement of learning and memory seen in animal models. PMID:20951128
Wang, Ting; Yang, Yuan-Jian; Wu, Peng-Fei; Wang, Wei; Hu, Zhuang-Li; Long, Li-Hong; Xie, Na; Fu, Hui; Wang, Fang; Chen, Jian-Guo
Assessment of dietary phytoestrogen intake via plant-derived foods in China.
The potential influence of dietary phytoestrogen exposure on human health during different life phases including early childhood is a matter of scientific debate. In order to improve the risk-benefit assessment of exposure to dietary phytoestrogen, reliable and age-stratified exposure data are desirable. For contributing to the database on phytoestrogen exposure, in the present study plant-derived foods from the Chinese market were analysed by LC-MS/MS for their contents of phytoestrogens, including daidzein, genistein, secoisolariciresinol, glycitein and coumestrol. The analytical data showed the presence of phytoestrogens in a concentration range of less than 0.1 to about 50 ?g g(-1). Dietary intake was assessed on the basis of average food intake data obtained from interviewing 1000 randomly selected people with the help of food frequency questionnaires. Based on the overall population sampled, the average total phytoestrogen intake was estimated at 232 ?g kg(-1) day(-1). Genistein contributed to about 66%, secoisolariciresinol and glycitein to about 10% each, and daidzein to about 7% of the overall intake. Coumestrol was present only in trace amounts. Age-related exposure assessment indicated that pre-pubertal children (aged 0-14 years) were exposed at the highest level with an average total phytoestrogen intake of 621 ?g kg(-1) day(-1). The substantially higher average exposure of children as compared with adults should trigger further research into the potential health effects of early life exposure to phytoestrogen. PMID:24950423
Hu, Xiao Juan; Song, Wan Rui; Gao, Li Ying; Nie, Shao Ping; Eisenbrand, Gerhard; Xie, Ming Yong
Content of meiosis activating sterols in equine follicular fluids: correlation to follicular size and dominance
Meiosis activating sterols (MAS) are pre-cholesterol sterols that can be isolated from follicular fluid (FF-MAS) or testes (T-MAS). Meiosis activating sterols trigger the resumption of meiosis in cultured meiotically competent oocytes. In the present work MAS, cholesterol and progesterone were assayed by HPLC in follicular fluids collected from pony mares at fixed days after the last ovulation. Follicles were divided
M. Baltsen; I. B. Břgh; A. G. Byskov
Lipid and stress dependence of amphotericin B ion selective channels in sterol-free membranes
The idea that amphotericin B (AmB) may not require sterols to form ion selective channels has recently been criticized on the grounds that egg phospholipids commonly used in experiments may contain small amounts of sterol which associate with AmB to form AmB\\/sterol pore channel structures. It was recently shown in this laboratory that modest osmotic stress can enhance the formation
Tracy Ruckwardt; Angela Scott; Jessica Scott; Peter Mikulecky; Scott C. Hartsel
Sterols from bivalves Calyptogena soyoae and Bathymodiolus septemdierum living in deep sea
From the two species of bivalves, Calyptogena soyoae around a cold seep and Bathymodiolus septemdierum near hydrothermal vents in the sea, sterols were isolated using high-pressure liquid chromatography analysis of the lipid\\u000a fraction guided by characteristic 1H NMR signals of the sterol skeleton. The minor sterol composition of C. soyoae included 24-methylenecycloartanal, cycloeucalenol, and obutusifoliol, which are known phytosterols. From
Shion Kawai; Yuuki Takada; Shinji Tsuchida; Ryusuke Kado; Junji Kimura
Use of Sterol and Bile Acid Biomarkers to Identify Domesticated Animal Sources of Fecal Pollution
The objective of this study was to demonstrate the use of chemical biomarkers (fecal sterols and bile acids) to identify selected\\u000a sources of fecal pollution in the environment. Fecal sterols and bile acids were determined for pig, horse, cow, and chicken\\u000a feces. Ten to twenty-six fresh fecal samples were collected for each animal, and the concentrations of fecal sterols (coprostanol,
Punam Tyagi; Dwayne R. Edwards; Mark S. Coyne
Is meiosis activating sterol (MAS) an obligatory mediator of meiotic resumption in mammals
In-vitro studies of mouse oocytes have provided evidence that two closely related sterols, subsequently named meiosis-activating sterols (MAS), can overcome the inhibitory effect of hypoxanthine on resumption of meiosis. These sterols are synthesized by cytochrome P450 (CYP) lanosterol 14?-demethylase (LDM), a key enzyme in cholesterol biosynthesis. Our studies in the rat with specific inhibitors and molecular approaches did not support
Alex Tsafriri; Xiumei Cao; Karen M Vaknin; Malka Popliker
Safety and nutritional assessment of GM plants and derived food and feed: the role of animal feeding trials.
In this report the various elements of the safety and nutritional assessment procedure for genetically modified (GM) plant derived food and feed are discussed, in particular the potential and limitations of animal feeding trials for the safety and nutritional testing of whole GM food and feed. The general principles for the risk assessment of GM plants and derived food and feed are followed, as described in the EFSA guidance document of the EFSA Scientific Panel on Genetically Modified Organisms. In Section 1 the mandate, scope and general principles for risk assessment of GM plant derived food and feed are discussed. Products under consideration are food and feed derived from GM plants, such as maize, soybeans, oilseed rape and cotton, modified through the introduction of one or more genes coding for agronomic input traits like herbicide tolerance and/or insect resistance. Furthermore GM plant derived food and feed, which have been obtained through extensive genetic modifications targeted at specific alterations of metabolic pathways leading to improved nutritional and/or health characteristics, such as rice containing beta-carotene, soybeans with enhanced oleic acid content, or tomato with increased concentration of flavonoids, are considered. The safety assessment of GM plants and derived food and feed follows a comparative approach, i.e. the food and feed are compared with their non-GM counterparts in order to identify intended and unintended (unexpected) differences which subsequently are assessed with respect to their potential impact on the environment, safety for humans and animals, and nutritional quality. Key elements of the assessment procedure are the molecular, compositional, phenotypic and agronomic analysis in order to identify similarities and differences between the GM plant and its near isogenic counterpart. The safety assessment is focussed on (i) the presence and characteristics of newly expressed proteins and other new constituents and possible changes in the level of natural constituents beyond normal variation, and on the characteristics of the GM food and feed, and (ii) the possible occurrence of unintended (unexpected) effect