
apolypoprotein ii

apolypoprotein ii (apo-ii) anedi ksheeradaala sariiramlooni kovvula gvakriyalo palgone protein. oka upa rakam algimers vyaadhi mariyu hridaya sambandha vyaadhulalo chikkukundi. idhi maanavulalo "apo" janyuvu dwara encode cheyabadindi.
apolypoproteinlu anie piluvabade kovvu-bandhinche proteinla kutumbaaniki chendinadi apo-ii. prasaranalo, idhi chylomicron avasheshaalu, vldl, idl mariyu konni hcdl thoo sahaa aneka taragatula lipoprotein kanaalalo bhaagamgaa untundi. apo takkuva saandrata kaligina lipoprotein graahakamtho (ldlr) gananeeyamgaa sankarshana chendutundi, idhi triglyzaride-adhikamgaa unde lipoproteinla saadhaarana prosessing (catabolism) kuu avasaram. paridheeya kanajaalaalo, apo pradhanamgaa kaaleyam mariyu macrophasela dwara utpatti cheyabadutundi mariyu collustroll jeevakriyaku madhyavartitvam vahistundi. kendra naadii vyavasthalo, apo-ii pradhanamgaa austrocytela dwara utpatti cheyabadutundi mariyu collestraalnu apo graahakaala dwara neuronlaku ravana chestundi, ivi takkuva saandrata kaligina lipoprotein grahaka janyu kutumbaaniki chendinavi. apo-ii anedi medadulooni pradhana collustroll vahakamu. austrocytes nundi neuronlaku collustroll ravaanaaku apo-ii avasaram. sakriyam cheyabadina c1q thoo sanklishta nirmaanam dwara shaastreeya puuraka maargam yokka checkpoint inhibitorga apo arhata pondindi.
parinaamam.
apolypoproteinlu ksheeradaalaku matrame parimitam kaavu. aneka bhusambandhamaina mariyu samudra sakasherukaalu vaati yokka samskaranalanu kaligi unnaayi. chepa-tetrapad sii vibhajanaku mundu apok 1 yokka janyu nakilee dwara "apo" udbhavinchindani nammutaaru. 400 million samvatsaraala kritam. choanoflazelletlalo ilanti proteins kanipinchaayi, ivi anni jeevula udayaaniki mundu chaalaa paatha taragati proteins anie suuchistunnaayi.
moodu pradhana maanava yugmavikalpalu ("e4", "e3", "e2") sumaru 7.5 laksala samvatsaraala kritam primate-maanava vibhajana tarvaata udbhavinchaayi. eee yugmavikalpalu anevi samaanaarthaka utparivartanalu kaani vaati upa utpatti, ivi kaaryaacharanalo maarpulaku daariteesaayi. udbhavinchina modati yugmavikalpam e4. primate-maanava vibhajana taruvaata, maanava vamsamlo naalugu amaino aamlam maarpulu jarigaayi, veetilo moodu protein paniteerupai etuvanti prabhavam chuupaleedu (v174l, a18t, a135v). nalgava pratyaamnaayam (t61r) protein yokka kaaryaacharananu marche arjinin kosam oka thraeonine nuu vartakam chesindi. eee pratyaamnaayam primate-human vibhajana mariyu denisovan-human vibhajana madhya 6 million samvatsaraala antaramlo ekkado jarigindi, endukante denisovan "apo" loe sarigga adhe pratyaamnaayaalu kanugonabaddayi.
sumaru 220,000 samvatsaraala kritam, "apo 4" janyuvu yokka amaino aamlam 112 (sisa112argi) vadda systeine nundi arjinin pratyaamnaayam jarigindi, dheeni phalitamgaa "ii3" yugmavikalpam erpadindi. chivaraku, 80,000 samvatsaraala kritam, "apo 3" janyuvu yokka amaino aamlam 158 (aarga 158sais) vadda systeine pratyamnaayamgaa maroka arjinin "ii2" yugmavikalpanni srushtinchindi.
nirmaanam.
janyuvu.
apo" anae janyuvu, apolypoprotein sii1 (apok1) mariyu apolypoprotein sii2 (apok2) thoo kuudina samuuhamloo chromosome 19kii mapp cheyabadutundi. apo" janyuvu naalugu exanlu mariyu moodu intraanlanu kaligi untundi, mottam 3597 bays jatalatho untundi. "apo" liver x receptor (collustroll, kovvu aamlam mariyu glucose homeostasis yokka mukhyamaina niyantrakam) mariyu peroxisome proliferator-activated receptor γ, retinoid x receptorlatho heterodymerlanu yerparuchukune nuclear receptorla dwara transcriptionalga sakriyam cheyabadutundi. melanocytic kanaalalo "apo" janyu vyakteekarananu mitf dwara niyantrinchavacchu.
protein.
apo 299 amaino aamlaala podavu kaligi untundi mariyu bahula amphipathic α-heliklanu kaligi untundi. sphatika shaastra adhyayanala prakaram, keelu praantam protein yokka enn-mariyu sii-terminal praantaalanu kaluputundi. enn-terminal praantam (avasheshaalu 1-167) protein lopala dhruvetara vaipula unde vidhamgaa samaantara naalugu-helix kattanu yerparustundi. intalo, sii-terminal domine (avasheshaalu 206-299) moodu α-heliklanu kaligi untundi, ivi pedda bahirgata hydrophobic uparitalaanni yerparustaayi mariyu hydrogen bandhaalu mariyu uppu-vantenala dwara enn-terminal helix bundle domainloni vaatitho sankarshana chendutaayi. sii-terminal praantamloo takkuva saandrata kaligina lipoprotein receptor (ldlr)-binding sait kooda untundi.
polymorphisms.
"apo" anedi bahuroopakam, moodu pradhana yugma vikalpaalato (epsilon 2, epsilon 3, mariyu epsilon 4): "apo-ε2" (cys112, cys158), "apo-ε3" (cys112, arg158), mariyu "apo-ε4" (arg112, arg158). eee yugmavikalpa roopaalu 112 mariyu 158 sthaanaalalo okati ledhaa rendu amaino aamlalu matrame okadaanikokati bhinnamgaa unnappatikee, eee thedaalu apo nirmaanam mariyu paniteerunu maarustaayi.
apo yokka aneka takkuva-pounahpunya polymorphisms unnaayi. apo 5 valasa raetla aadhaaramgaa rendu uparakaalu e5f mariyu e5s loe vastundi. japan purushulalo 2.8% mandhi loe apo 5 ii5eff mariyu apo 7 kalipi kanugonabaddayi. apo 7 anedi apo 3 yokka parivartana, idhi 244 mariyu 245 sthaanaalalo glutamic aamlam avasheshaalanu bharti chese rendu lysine avasheshaalatho untundi.
itara rakshana janyuvula paraspara charyatho sahaa apo isopharmla gurinchi telusukovalasinavi chaalaa unnaayi. nijaaniki, apolypoprotein ε4 isopharm konni sandarbhaallo itara isopharmla kante abhignaa ksheenataku vyatiraekamgaa marinta rakshanagaa untundi, kabatti abhignaa, algimers vyaadhi abhivruddhi, hridaya sambandha vyaadhi, telomir kluptam modalaina vaatipai apo polymorphisms prabhavam gurinchi nirnayaatmaka prakatanalu chese mundu jaagratta vahinchaalani salaha istaaru. eee pratikuula phalitaalu pratiroopam cheyani oke adhyayanala nundi vachayani mariyu eee isopharm gurinchi tanikhi cheyani oohalapai parisoedhana aadharapadi undani aneka adhyayanalu perkonnaayi. 2007 natiki, apo polymorphisms chinna vayassu samoohaalalo gnaanaanni prabhaavitam chestayani (yuva apo 4 vayassu samoohaalalo episodic memory saamarthyam mariyu naadii saamarthyam peragadam tappa), ledhaa apo 4 isopharm vyaktulanu yea antu vyaadhiki ekkuva pramaadaaniki gurichestundane aadharalu laevu.
edemaina, apo 4 yugmavikalpam mariyu algimers vyaadhi madhya sambandham alpasankhyaaka samoohaalalo vaari caucassian sahacharulatho poliste bhinnamgaa balaheenamgaa unnatlu choopabadindi. apo 4 yugmavikalpaaniki sajaateeyamgaa unna hysponics/laatinolu mariyu african americanlaku algimers vyaadhi abhivruddhi chendadaaniki varusaga 2.2 mariyu 5.7 retlu asamaanatalu unnaayi. yugmavikalpaaniki sajaateeyamgaa unna kakasianlu 12.5 retlu asamaanata kaligi unnaaru.
function.
apo lipidlu, kovvulo karige vitaminlu mariyu collestraalnu shosharasa vyavasthaloki, aapai raktamloki ravana chestundi. idhi pradhanamgaa kaaleyamlo samslaeshanha cheyabadutundi, conny medadu, moothrapindaalu mariyu pleehamu vanti itara kanajaalaalo kooda kanugonabadindi. naadii vyavasthalo, neuronal kaani kana rakalu, mukhyamgaa austroglia mariyu microglia, apo yokka praadhamika utpattidaarulu, ayithe neuronlu pradhaanyamgaa apo kosam grahakalanu vyaktam chestaayi. parinaamatmakamgaa samrakshinchabadina ldlr kutumbaaniki chendina apo kosam prastutam gurtinchabadina edu ksheerada grahakaalu unnaayi.
lipoprotein jeevakriya mariyu hridaya sambandha vyaadhulalo apo praamukhyata kosam modatlo gurtinchabadindi. apolo lopaalu kutumba diasbetalipoproteinemia ledhaa type III hyperlipoproteinemia (hclp III) kuu daariteestaayi, dheenilo perigina plasma collustroll mariyu triglyzarides chylomicron, vldl mariyu ldl yokka balaheenamaina clearance phalitamgaa untaayi. iteevala, algimers vyaadhi (AD), roganirodhaka niyantrana mariyu ghnaanamtho sahaa lipoprotein ravaanaaku neerugaa sambandham laeni aneka jeeva prakriyalalo daani paatra kosam idhi adhyayanam cheyabadindi. khachitamaina vidhanalu spashtam cheyabadavalasi unnappatikee, apo yugmavikalpam dwara encode cheyabadina apo yokka isopharm 4, yaantrika gaayam taruvaata calcium ayan sthaayilu mariyu apoptosisto mudipadi undhi.
roganirodhaka niyantrana rangamlo, tii sell vistarananu anachiveyadam, macrophage paniteeru niyantrana, sahaja killer tii sell kuu lipid antigen pradarsana soulabhyam (sidi1 dwara) thoo paatu vaapu mariyu aakseekarana yokka modulation vanti aneka roganirodhaka prakriyalatho apo yokka paraspara charyanu perugutunna adhyayanalu suuchistunnaayi. apo macrophasela dwara utpatti avutundi mariyu apo sraavam pbmcloni shaastreeya monocytelaku parimitam cheyabadindani choopabadindi, mariyu monocytela dwara apo sraavam inflammatory cytokins dwara niyantrinchabadutundi mariyu tgf-beata dwara niyantrinchabadutundi.
clinical praamukhyata.
algimers vyaadhi.
2012 natiki, vividha jaathi samoohaalalo aalasyamgaa praarambhamayye chedurumaduru algimers vyaadhi (AD) kii e4 roopaantaram atipedda janyu pramaada karakamga undhi. ayithe, eee4 roopaantaram prati janabhalo pramaadamtoe sambandham kaligi undadu. nigerian prajalu prapancha janabhalo "apo 4" yugmavikalpam yokka atyadhika gamaninchina pounahpunyaanni kaligi unnaaru, conny vaarilo prakatana arudu. idhi vaari takkuva collustroll sthaayila kaaranamgaa undavacchu. rendu ii4 yugmavikalpala yokka caucassian mariyu japanese vahakalu 75 samvatsaraala vayassulo prakatana abhivruddhi chendhe pramaadam 10 nundi 30 retlu untundi, yea ii4 yugmavikalpalanu kaligi laeni vaatitho poliste. idhi amilaydto paraspara charya valla sambhavinchavachhu. algimers vyaadhi peptide beata-amyloid yokka aggregatela nirmaanam dwara vargeekarinchabadutundi. apolypoprotein ii kanaala lopala mariyu madhya eee peptide yokka proteolytic vichchinnatanu penchutundi. eee praticharyalanu prothsahinchadamlo isopharm apo-ε4 itarula vale prabhaavavantamgaa undadu, phalitamgaa aaa janyu vaividhyam unna vyaktulalo prakatanaku gurayye avakaasam perugutundi.
iteevala, algimers vyaadhi yokka amyloid parikalpana prashninchabadindi, mariyu "sains" loe oka vyaasam "poganu tolaginchadam valla manta aaripokapovadam, amyloid phalakaalanu tagginchadam valla algimers vyaadhi yokka gatini prabhaavitam cheyakapovachhu" anie perkondi."algimers vyaadhiloo relin signalling keelaka prakriyalalo okatigaa udbhavistundi mariyu eee4 roopaantaram neuronal relin grahakaalalo okataina apoer2 thoo sankarshana chendutundani choopabadindi, tadwara relin signalingnu addukuntundi anae vaastavaanni batti chellubaatu ayye amyloid parikalpana laenappatikee eee4 roopaantaram kaligi unna paatranu ippatikee puurtigaa vivarinchavacchu.
prakatana rogulalo 40-65% kaneesam ε4 yugmavikalpam yokka oka kaapeeni kaligi unnappatikee, "apo 4" vyaadhini nirnayinchedi kaadu. prakatana unna rogulalo kaneesam moodinta oka vanthu mandhi "apo 4" pratikuulamgaa untaaru mariyu konni "apo 4" homojaigotlu eee vyaadhini eppuduu abhivruddhi cheyavu. ayinappatikee rendu ε4 yugmavikalpalu unnavaariki prakatana abhivruddhi chendhe pramaadam 20 retlu untundi. apo 2" yugmavikalpam prakatanalo rakshana paatranu pooshinchavacchani kooda aadharalu unnaayi. anduvalla, algimers vyaadhiki mariyu antakumundu vayassulo atyanta pramaadakaramaina janyuroopam apo 4,4. janyuroopam apo 3,3 nuu oka pramaanamgaa upayoginchadam (eee janyuroopam unna vyaktulu 1 pramaada sthaayini kaligi unnatlu pariganistaaru) mariyu tella janaabhaaku matrame, janyuroopam apo 4,4 unna vyaktulu algimers vyaadhini abhivruddhi cheyadamlo 14.9 yokka asamaana nishpattini kaligi untaaru. apo 3,4 janyuroopam unna vyaktulu 3.2 yokka asamaana nishpattini edurkontaaru, mariyu 2 yugmavikalpam mariyu 4 yugmavikalpam (apo 2,4) yokka coppy unna vyaktulu 2.6 yokka asamaana nishpattini kaligi untaaru. 2 yugmavikalpam mariyu 3 yugmavikalpam (apo 2,3) loe okkokka coppy unna vyaktulu 0.6 yokka asamaana nishpattini kaligi untaaru. 2 yugmavikalpam (apo 2,2) yokka rendu kaapeelu unna vyaktulu kooda 0.6 yokka asamaana nishpattini kaligi untaaru.
apo 4 anedi oka vyaktiki algimers vyaadhi vachhe avakaasaalanu baga penchutundani kanugonabadinappatiki, 2002 adhyayanam, apo yugmavikalpala kalayika unna vyaktulalo, adhika seeram mottam collustroll mariyu madhya-jeevitakaalamlo adhika raktapotu swatantra pramaada karakalu anie nirdhaarinchindi, ivi kalisi aaa vyakti taruvaata prakatnanu abhivruddhi chese pramaadaanni daadaapu moodu retlu penchutaayi. tama dayta nundi anchanaa vaestuu, kontamandi parisoedhakulu seeram collustroll sthaayilanu tagginchadam valla algimers vyaadhi vachhe pramaadaanni tagginchavacchani suuchimchaaru, vaariki rendu apo 4 yugmavikalpalu unnappatikee, tadwara prakatana vachhe pramaadaanni tommidi ledhaa padhi retlu nundi kevalam rendu retlu varaku taggistundi.
chaalaa vayasula mariyu apo janyuroopaalalo purushula kante mahilalu prakatanalanu abhivruddhi chese avakaasam ekkuvagaa untundi. ε4 yugmavikalpam unna mundastu anaaroogyam unna mahilalu purushula kante gananeeyamgaa ekkuva naraala vaiphalyaanni kaligi untaaru.
"apo-ii4" anedi prakatanaku matrame kakunda swachchamaina alfa-sainyuuklinoopati rogaalalo chittavaikalyam pramaadaanni kooda penchutundi. hippocompal ksheenatapai "apo"-ε4 prabhavam marinta vistrutamaina neurodegenerationku mundu telikapati dasalalo prakatana praarambhamlo marinta prabalamgaa untundani soochinchabadindi.
atherosclerosis.
apolypoprotein-ii janyuvu (apo-/-) laeni nock avt elukalu adhika kovvu aaharam icchinappudu teevramaina hyper collusterolemianu abhivruddhi chestaayi.
malaria.
apo-/-nakout elukalu mastishka malaria yokka gurtinchadagina ksheenata mariyu manugadanu penchutaayi, alaage medadulooni paraannajeevulu mariyu tii kanaala vibhajana taggutundi, bahusha rakta-medadu avarodham yokka rakshana kaaranamgaa. maanava adhyayanalu apo 2 polymorphism munupati sankramanatho sahasambandham kaligi undani, apo 3/4 polymorphisms teevramaina malaria sambhaavyatanu penchutaayani choopinchaayi.