Antioxidant enzyme inhibitors enhance peroxynitrite-induced cell death in U937 cells |
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Authors: | Eun Sun Yang Jeen-Woo Park |
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Institution: | (1) Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu, 702-701, Korea |
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Abstract: | 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. |
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Keywords: | Peroxynitrite Antioxidant enzymes Cell death Redox status |
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