Antioxidant enzyme inhibitors enhance singlet oxygen-induced cell death in HL-60 cells.
Singlet oxygen is a highly reactive form of molecular oxygen that may harm living systems by oxidizing critical cellular macromolecules and it also promotes deleterious processes such as cell death. The protective role of antioxidant enzymes against singlet oxygen-induced oxidative damage in HL-60 cells was investigated in control and cells pre-treated with diethyldithiocarbamic acid, aminotriazole and oxlalomalate, specific inhibitors of superoxide dismutase, catalase and NADP+-dependent isocitrate dehydrogenase, respectively. Upon exposure to rose bengal (20 microM)/light (15 min), which generates singlet oxygen, to HL-60 cells, the viability was lower and the lipid peroxidation and oxidative DNA damage were higher in inhibitor-treated cells as compared to control cells. We also observed the significant increase in the endogenous production of reactive oxygen species as well as the significant decrease in the intracellular GSH level in inhibitor-treated HL-60 cells exposed to singlet oxygen. Upon exposure to rose bengal (3 microM)/light (15 min), which induced apoptotic cell death, a clear inverse relationship was observed between the control and inhibitor-treated HL-60 cells in their susceptibility to apoptosis. These results suggest that antioxidant enzymes play an important role in cellular defense against singlet oxygen-induced cell death including necrosis and apoptosis.
Kim
Sun Yee
SY
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu, 702-701, South Korea.
Lee
Su Min
SM
Park
Jeen-Woo
JW
D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis; D016923:Cell Death; D002469:Cell Separation; D004249:DNA Damage; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D015227:Lipid Peroxidation; D009336:Necrosis; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D026082:Singlet Oxygen / Q000378:metabolism
D000975:Antioxidants; D004791:Enzyme Inhibitors; D026082:Singlet Oxygen; D005978:Glutathione; D010100:Oxygen