RI and CI alter molecular mechanisms determining survival. RI and CI activate 4 signal transduction pathways. 1. RI and CI activate NF-κB. NF- κB binds onto 10 motif sites on the promoter region of iNOS gene to transcribe and translate iNOS protein. This protein catalyzes NO production so as to produce high levels of peroxynitrite, a free radical to nitrate other proteins. The free radical stimulates NF-κB that increases circulating cytokine/chemokine concentration and vice versa. As a result, cell death occurs. 2. RI and CI activate MAPK that is known anti-survival. 3. RI and CI decrease NRF1 and NRF2 so that B-ATP synthase, cytochrome c and cytochrome c oxidase IV are reduced. Then, ATP production is reduced, and cell death occurs. 4. RI and CI increase miR-34a that is evident to activate NF- κB. RI radiation injury, CI combined injury, MAPK mitogen-activated protein kinase, NF-κB nuclear factor-keppaB, Foxo3 forkhead box O3, PGC-1α peroxisome proliferator-activated receptor gamma coactivator 1-alpha, NRF nuclear respiratory factor, iNOS inducible nitric oxide, ROS reactive oxygen species, RNS reactive nitrogen species, IL interleukin, TNF tumor necrosis factor
Kiang, J.G., Olabisi, A.O.
CC BY 4.0
Kiang, J.G., Olabisi, A.O. Radiation: a poly-traumatic hit leading to multi-organ injury. Cell Biosci 9, 25 (2019). <a rel="nofollow" class="external free" href="https://doi.org/10.1186/s13578-019-0286-y">https://doi.org/10.1186/s13578-019-0286-y</a>