Ramdial Kristina, Franco Maria Clara, Estevez Alvaro G
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL32827,United States.
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL32827,United States.
Brain Res Bull. 2017 Jul;133:4-11. doi: 10.1016/j.brainresbull.2017.05.008. Epub 2017 Jun 24.
Peroxynitrite (ONOO) is a strong biological oxidant formed by the diffusion-limited reaction of nitric oxide (NO) and superoxide anion (O). It has long been theorized that peroxynitrite generation could be the cause in a number of pathological conditions ranging from atherosclerosis to inflammatory, autoimmune, heart and neurodegenerative diseases. Its relatively long biological half-life and high reactivity allows peroxynitrite to oxidize a number of different targets in the cell. In physiologically relevant conditions peroxynitrite can directly react with thiols, or the radical products of peroxynitrite decomposition may indirectly oxidize other cellular components such as lipids, proteins and DNA. Downstream, oxidative modifications caused by peroxynitrite trigger cell death by a variety of mechanisms depending on the concentration of the oxidant. Peroxynitrite stimulates necrosis, apoptosis, autophagy, parthanatos and necroptosis. Here we review the mechanisms activated by peroxynitrite to cause neuronal death.
过氧亚硝酸根（ONOO⁻）是一种强生物氧化剂，由一氧化氮（NO）和超氧阴离子（O₂⁻）的扩散限制反应形成。长期以来，理论认为过氧亚硝酸根的产生可能是导致从动脉粥样硬化到炎症、自身免疫、心脏和神经退行性疾病等多种病理状况的原因。其相对较长的生物半衰期和高反应活性使过氧亚硝酸根能够氧化细胞内多种不同的靶点。在生理相关条件下，过氧亚硝酸根可直接与硫醇反应，或者过氧亚硝酸根分解产生的自由基产物可能间接氧化其他细胞成分，如脂质、蛋白质和DNA。在下游，过氧亚硝酸根引起的氧化修饰根据氧化剂的浓度通过多种机制触发细胞死亡。过氧亚硝酸根可刺激坏死、凋亡、自噬、PARP-1依赖性细胞死亡和坏死性凋亡。在此，我们综述过氧亚硝酸根激活导致神经元死亡的机制。
