NO and apoptosis

Mitochondrial function. NO is able to react with transition metals such as iron, including those contained within haem groups. Even at low NO concentrations there is competition between oxygen and NO for reversible binding to cytochrome c oxidase. If mitochondrial 02 is low respiration slows, which may confer anti-apoptotic benefit to the cell. As NO concentration rises and peroxynitrite is formed, electron transport is irreversibly inhibited, there is increased production of superoxide and other reactive oxygen species and apoptosis occurs. 

There is great interest in the mechanisms of cell death since better understanding might lead to therapy that slows the rate of aging and prevents or treats human disease. Two major processes of cell death have been described, apoptosis and neaosis other alternative pathways generally are variations of these (Formigli et al, 2000 Sperandio et al, 2000 Reed, 1999). Some of the intracellular events related to these types of death have been discovered (Reed, 2000). After exposure to noxious stimuli, the balance between antiapoptotic and proapoptotic influences can result in either survival or death. Many of these variable influences and the subsequent downstream concatenated events involve oxidation, which targets cellular components such as DNA, cellular proteins and membrane phospholipids. Our laboratory and others have studied the role of the redox-active cellular constituents nitric oxide ( NO) and membrane phospholipid... 

Wu ML, Li H, Wu DC, Wang XW, Chen XY, et al. 2005. CYPlAl and CYPIBI expressions in medulloblastoma cells are AhR-independent and have no direct link with resveratrol-induced differentiation and apoptosis. Neurosci Lett 384 33-37. 

The above examples point out at the direct stimulation of apoptosis by nitric oxide. At the same time, the exclusively rapid reaction of NO with superoxide always suggests the possibility of peroxynitrite participation in this process [141] correspondingly, the role peroxynitrite in the stimulation of apoptosis has been considered. Bonfoco et al. [144] has found that the producers of low peroxynitrite concentrations during the exposure of cortical neurons to the low level of NMDA or the use of peroxynitrite donors resulted in an apoptosis in neurons, while the high concentrations of peroxynitrite induced necrotic cell damage. The formation of peroxynitrite is apparently responsible for NO-stimulated apoptosis in superoxide-generating transformed fibroblasts because nontransformed cells, which do not produce superoxide, were not affected by nitric oxide [145]. It is of interest that proapoptotic effect of peroxynitrite may depend on the cell type. Thus, the formation of peroxynitrite enhanced the NO-induced apoptosis in glomerular endothelial cells, while superoxide inhibited the formation of ceramide and apoptosis in these cells exposed to nitric oxide probably due to peroxynitrite formation... 

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