Brown Guy C, Borutaite Vilmante
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
Free Radic Biol Med. 2002 Dec 1;33(11):1440-50. doi: 10.1016/s0891-5849(02)01112-7.
Nitric oxide (NO) or its derivatives (reactive nitrogen species, RNS) inhibit mitochondrial respiration in two different ways: (i) an acute, potent, and reversible inhibition of cytochrome oxidase by NO in competition with oxygen; and, (ii) irreversible inhibition of multiple sites by RNS. NO inhibition of respiration may impinge on cell death in several ways. Inhibition of respiration can cause necrosis and inhibit apoptosis due to ATP depletion, if glycolysis is also inhibited or is insufficient to compensate. Inhibition of neuronal respiration can result in excitotoxic death of neurons due to induced release of glutamate and activation of NMDA-type glutamate receptors. Inhibition of respiration may cause apoptosis in some cells, while inhibiting apoptosis in other cells, by mechanisms that are not clear. However, NO can induce (and inhibit) cell death by a variety of mechanisms unrelated to respiratory inhibition.
一氧化氮（NO）或其衍生物（活性氮物质，RNS）通过两种不同方式抑制线粒体呼吸：（i）NO与氧气竞争，对细胞色素氧化酶进行急性、强效且可逆的抑制；以及（ii）RNS对多个位点进行不可逆抑制。NO对呼吸的抑制可能通过多种方式影响细胞死亡。如果糖酵解也受到抑制或不足以补偿，呼吸抑制会因ATP耗竭导致坏死并抑制细胞凋亡。神经元呼吸抑制可因谷氨酸诱导释放和NMDA型谷氨酸受体激活而导致神经元兴奋性毒性死亡。呼吸抑制可能通过尚不清楚的机制在某些细胞中导致细胞凋亡，而在其他细胞中抑制细胞凋亡。然而，NO可通过多种与呼吸抑制无关的机制诱导（和抑制）细胞死亡。
