Nitric oxide apoptosis induction

Estevez, A. G.,Crow, J. P., Sampson, J. B. etal. Induction of nitric oxide-dependent apoptosis in motor neurons by zinc-deficient superoxide dismutase. Science 286 2498-2500,... 

Exposure to trichothecenes at levels that partially inhibit translation upregulates expression of many inflammatory and immune-related genes including macrophage, Thl and Th2 cytokines as well as chemokines, cyclooxygenase 2 and inducible nitric oxide synthase.1518 Contrastingly, suppressive effects of trichothecenes on leukocyte function are intimately linked with the induction of apoptosis as has been demonstrated in macrophages, T cells and B cells both in vivo and in vitro.19-20... 

Another central element of the Grishko hypothesis is the upregulation of inducible nitric oxide synthase (iNOS). Since the induction of iNOS is often associated with extensive nitric oxide formation, it is commonly a toxic event. However, nitric oxide formation is not detrimental in all cell types. Dimmeler et al. (1997) found that nitric oxide protects human endothelial cells against angiotensin II-mediated apoptosis. A key variable appears to be the amount of nitric oxide produced. In the cardiomyocyte, sufficient levels of nitric oxide are generated to cause the formation of toxic levels of peroxynitrite, while in endothelial cells, ROS, rather than reactive nitrogen species, appear to be the toxic mediators of apoptosis. 

NO, derived from L-arginine (L-Arg) by the enzyme nitric oxide synthase (NOS), is involved in the regulation of relevant physiological and pathophysiological functions. The mechanisms by which NO exerts its effects include activation of guanylate cyclase, formation of peroxynitrite, apoptosis, and COX regulation [96]. Apoptosis induction mediated by NO involves mitochondrial depolarization and is blocked by Bcl-2 overexpression [97]. 

Tea polyphenols exhibit a variety of biological properties, including antioxidative effects [6], inhibition of extracellular mitotic signals [7], inhibition of cell cycle at the G1 phase [8], suppression of inducible nitric oxide synthase (iNOS) [7, 9], and induction of apoptosis in cancer cells [10]. The natural history of carcinogenesis and cancer provides a strong rationale for a preventive approach to the control of this disease and leads to considerations of the possibility of active pharmacological intervention, or chemoprevention, to arrest or reverse the carcinogenesis prior to invasion and metastasis [11. 12]. 

Jan JT, Griffin DE. Induction of apoptosis by Sindbis virus occurs at cell entry and does not require virus replication. Journal of Virology 1999 73(12) 10296-10302 Kapoor R, Davies M, Smith KJ. Temporary axonal conduction block and axonal loss in inflammatory neurological disease. A potential role for nitric oxide Annals of the New York Academy of Sciences 1999 893 304—308... 

Heneka, M.T., Loschmann, P.A., Gleichmann, M., Weller, M., Schulz, J.B., Wullner, U., and Klockgether, T. (1998). Induction of nitric oxide synthase and nitric oxide-mediated Apoptosis in neuronal PC 12 cells after stimulation with tumor necrosis factor-alpha/lipopolysaccharide. J. Neurochem. 71, 88-94. 

Shami, P.J., Sauls, D.L., and Weinberg, J.B. (1998). Schedule and concentration-dependent induction of apoptosis in leukemia cells by nitric oxide. Leukemia 12,1461-1466. 

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