Regulation of nitric oxide-induced apoptosis by sensitive to apoptosis gene protein.
Sensitive to apoptosis gene (SAG) protein, a novel zinc RING finger protein that protects mammalian cells from apoptosis by redox reagents, is a metal chelator and a potential reactive oxygen species (ROS) scavenger, but its antioxidant properties have not been completely defined. Nitric oxide (NO), a radical species produced by many types of cells, is known to play a critical role in many regulatory processes, yet it may also participate in collateral reactions at higher concentrations, leading to cellular oxidative stress. In this report, we demonstrate that modulation of SAG expression in U937 cells regulates NO-induced apoptosis. When we examined the protective role of SAG against NO-induced apoptosis with U937 cells transfected with the cDNA for SAG, a clear inverse relationship was observed between the amount of SAG expressed in target cells and their susceptibility to apoptosis. We also observed the significant decrease in the endogenous production of ROS and oxidative DNA damage in SAG-overexpressed cells compared to control cells upon exposure to NO. These results suggest that SAG plays an important protective role in NO-induced apoptosis, presumably, through regulating the cellular redox status.
Yang
Eun Sun
ES
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702701, Korea.
Park
Jeen-Woo
JW
D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D004249:DNA Damage; D018076:DNA, Complementary / Q000235:genetics; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D009569:Nitric Oxide / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells / Q000166:cytology / Q000187:drug effects; D044767:Ubiquitin-Protein Ligases
D018076:DNA, Complementary; D016166:Free Radical Scavengers; D016601:RNA-Binding Proteins; D009569:Nitric Oxide; C118307:RNF7 protein, human; D044767:Ubiquitin-Protein Ligases; D020169:Caspases