Nitric Oxide as a Pro-apoptotic as well as Anti-apoptotic Modulator

• Published in: BMB reports Vol. 35; no. 1; pp. 116 - 126
• Main Authors: Choi, Byung-Min, Pae, Hyun-Ock, Jang, Seon-Il, Kim, Young-Myeong, Chung, Hun-Taeg
• Format: Journal Article
• Language: English
• Published: Korea (South) 31.01.2002
• Subjects: Animals; Apoptosis; Arginine - chemistry; Caspases - metabolism; Catalytic Domain; Cell Survival; Ceramides - metabolism; Cysteine - chemistry; Cytochromes c - metabolism; Cytosol - metabolism; Gene Expression Regulation; Humans; Lipopolysaccharides - chemistry; Mitochondria - metabolism; Necrosis; Nitric Oxide - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; Sulfhydryl Compounds - chemistry; Transcription, Genetic; Tumor Suppressor Protein p53 - metabolism; Up-Regulation
• ISSN: 1976-6696; 1225-8687
• DOI: 10.5483/BMBRep.2002.35.1.116

Nitric oxide (NO), synthesized from L-arginine by NO synthases, is a small, lipophilic, diffusible, highly reactive molecule with dichotomous regulatory roles in many biological events under physiological and pathological conditions. NO can promote apoptosis (pro-apoptosis) in some cells, whereas it inhibits apoptosis (anti-apoptosis) in other cells. This complexity is a consequence of the rate of NO production and the interaction with biological molecules such as metal ion, thiol, protein tyrosine, and reactive oxygen species. Long-lasting overproduction of NO acts as a pro-apoptotic modulator, activating caspase family proteases through the release of mitochondrial cytochrome c into cytosol, up-regulation of the p53 expression, and alterations in the expression of apoptosis-associated proteins, including the Bcl-2 family. However, low or physiological concentrations of NO prevent cells from apoptosis that is induced by the trophic factor withdrawal, Fas, TNFalpha/ActD, and LPS. The anti-apoptotic mechanism is understood on the basis of gene transcription of protective proteins. These include: heat shock protein, hemeoxygenase, or cyclooxygenase-2 and direct inhibition of the apoptotic executive effectors caspase family protease by S-nitrosylation of the cysteine thiol group in their catalytic site in a cell specific way. Our current understanding of the mechanisms by which NO exerts both pro- and anti-apototic action is discussed in this review article.