Nitric oxide cell apoptosis

Apoptosis is induced by various intra- and extracellular stimuli, and recently nitric oxide was reported to induce apoptosis in cultured cerebellar granule cells and cultured cortical neurons. The toxicity of nitric oxide is mainly ascribed to peroxynitrite, a reaction product of nitric oxide with superoxide (Figure 13.8). Cells producing an increased amount of SOD (superoxide, superoxide oxidoreductase EC 1.15.1.1) are resistant to nitric oxide-mediated apoptosis. In contrast, superoxide levels that have been increased by downregulation of Cu,Zn-SOD lead to apoptotic cell death in PC 12 cells, which required the reaction with nitric oxide to generate peroxynitrite. Peroxynitrite itself was found to induce apoptosis in PC12 cells and in cultured cortical neurons. 

McCarthy NJ, et al. Inhibition of Ced-3/ICE-related proteases does not prevent ceU death induced by oncogenes, DNA damage, or the Bcl-2 homologue Bak. J. Cell Biol. 1997 136 215-227. Hirsch T, et al. The apoptosis-necrosis paradox. Apoptogenic proteases activated after mitochondrial permeability transition determine the mode of ceU death. Oncogene 1997 15 1573-1581. Leist M, et al. Inhibition of mitochondrial ATP generation by nitric oxide switches apoptosis to necrosis. Exp. Cell Res. 1999 249 396-403. 

A. Amore, P. China, G. Conti, F. Cemtti, N. Bagheri, S. N. Emancipator, and R. Coppo, Amadori-configurated albumin induces nitric oxide-dependent apoptosis of endothehal cells A possible mechanism of diabetic vasculopathy, Nephrol. Dial. Transplant., 19 (2004) 53-60. 

Kuo ML, Chau YP, Wang JH et al. Inhibitors of poly(ADP-ribose) polymerase block nitric oxide-induced apoptosis but not differentiation in human leukemia HL-60 cells. Biochem Biophys Res Commun 1996 219(2) 502-508. 

Pervin, S., Singh, R., Freije, W.A., Chaudhuri, G. (2003). MKP-l-induced dephosphorylation of extracellular signal-regulated kinase is essential for triggering nitric oxide-induced apoptosis in human breast cancer cell lines implications in breast cancer. Cancer Res. 63, 8853-8860. 

Wenzel, U., Kuntz, S., De Sonsa, U.J., and Daniel, H. (2003). Nitric oxide suppresses apoptosis in hnman colon cancer cells by scavenging mitochondrial superoxide anions. Int. J. Cancer. 705(5), 666-675. 

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. 

Gansauge, S., Nussler, A.K., Beger, H.G., and Gansauge, F. (1998). Nitric oxide-induced apoptosis in human pancreatic carcinoma cell lines is associated with a Gl-arrest and an increase of the cyclin-dependent kinase inhibitor p21WAFl/CIPl. Cell Growth Differ. 9,611-617. 

Jeon, H.K., Choi, S.U., and Jung, N.P. (2005). Association of the erkl/2 and p38 kinase pathways with nitric oxide-induced apoptosis and cell cycle arrest in colon cancer cells. Cell Biol. Toxicol. 21, 115-125. 

Lim, S., Hung, A.C., and Porter, A.G. (2009). Focused per screen reveals p53 dependence of nitric oxide-induced apoptosis and up-regulation of maspin and plasminogen activator inhibitor-1 in tumor cells. Mol. Cancer Res. 7,55-66. 

Rieder, J., Jahnke, R., Schloesser, M., Seibel, M., Czechowski, M., Marth, C., and Hoffmann, G. (2001). Nitric oxide-dependent apoptosis in ovarian carcinoma cell lines. Gynecol. Oncol. 82, 172-176. 

Nishikawa, M., Sato, E.F., Kuroki, T., Utsumi, K., and Inoue, M. (1998). Macrophage-derived nitric oxide induces apoptosis of rat hepatoma cells in vivo. Hepatology. 25(6), 1474—1480. 

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... 

The effect of MAPK activation on cellular processes that affect cell function and the resulting pharmacology has been delineated using modem techniques such as knock-out cells and animals [1,3,6]. Activation of MAPK in inflammatory cells such as T-cells, B-cells, macrophages and eosinophils leads to expression and/or activation of pro-inflammatory genes and mediators such as interleukin-1(3 (IL-1(3), TNFa, IL-6, chemokines [e.g., IL-8, macrophage inflammatory factor-1 a, (3 (MIP-la,[3)J, MMPs and toxic molecules such as free radicals and nitric oxide [1,3]. These pro-inflammatory mediators induce cellular proliferation, differentiation, survival, apoptosis and tissue degradation/destruction and help induce chronic inflammation. Inhibition of any one or more of the MAPK family... 

Wang, X., A. Zalgenstein, and M. Oeen, Nitric oxide promotes p53 nuclear retention and sensitizes neuroblastoma cells to apoptosis by ionizing radiation. Cell Death Differ,... 

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... 

Esaki, T., Hayashi, T, Muto, E., Kano, H., Kumar, T.N., Asai, Y., Sumi D., and Iguchi, A., 2000, Expression of nitric oxide synthase and Eas/Fas ligand correlates with the incidence of apoptosis cell death in atheromatous plaques ofhuman coronary arteries, Nitric Oxide 4 561-571. 

Sphingosine 1 -phosphate protects human umbilical vein endothelial cells from semm-depiived apoptosis by nitric oxide production, J. Biol. Chem. 276 10627-10633. 

K. Dvorakova, H. Bernstein, C. Bernstein, H. Holubec and H. Garewal, Caspase-6 mediated cleavage of guanylate cyclase alpha 1 during deoxycholate-induced apoptosis protective role of the nitric oxide signalling module. Cell Biol. Toxicol, 2003, 19(6), 373. 

Oxidized LDL induces apoptosis in vascular cells including macrophages and this is prevented by nitric oxide. 

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