Antioxidant enzyme inhibitors enhance peroxynitrite-induced cell death in U937 cells.
Peroxynitrite, a potent physiological inorganic toxin, is known to play a critical role in cellular oxidative damage. The protective role of antioxidant enzymes against peroxynitrite-induced oxidative damage in U937 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 1 mM 3-morpholinosydnomine N-ethylcarbamide (SIN-1), a generator of peroxynitrite through the reaction between nitric oxide and superoxide anion, to U937 cells, the viability was lower and the protein oxidation, lipid peroxidation and oxidative DNA damage reflected by an increase in 8-hydroxy-2'-deoxyguanosine, were higher in the inhibitor-treated cells as compared to the control cells. We also observed the significant increase in the endogenous production of reactive oxygen species, as measured by the oxidation of 2'7'-dichlorodihydrofluorescin as well as the significant decrease in the intracellular GSH level in the inhibitor-treated U937 cells upon exposure to SIN-1. These results suggest that antioxidant enzymes play an important role in cellular defense against peroxynitrite-induced cell death.
Yang
Eun Sun
ES
Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu, Korea.
Park
Jeen-Woo
JW
D000640:Amitrole / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D004050:Ditiocarb / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010070:Oxalates / Q000378:metabolism; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D020298:U937 Cells
D000975:Antioxidants; D004791:Enzyme Inhibitors; D010070:Oxalates; D017392:Thiobarbituric Acid Reactive Substances; D030421:Peroxynitrous Acid; C015407:oxalomalic acid; D004050:Ditiocarb; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+); D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D000640:Amitrole