Ethanol induces peroxynitrite-mediated toxicity through inactivation of NADP+-dependent isocitrate dehydrogenase and superoxide dismutase

Biochimie
Eun Sun YangJeen-Woo Park

Abstract

It has been reported that chronic alcohol administration increases peroxynitrite hepatotoxicity by enhancing concomitant production of nitric oxide and superoxide. Several studies have shown the importance of superoxide dismutase (SOD) in protecting cells against ethanol-induced oxidative stress. Recently, we demonstrated that the control of cytosolic and mitochondrial redox balance and the cellular defense against oxidative damage is one of the primary functions of NADP+-dependent isocitrate dehydrogenase (ICDH) through to supply NADPH for antioxidant systems. In this report, we demonstrate that ethanol induces the peroxynitrite-mediated cytotoxicity in HepG2 cells through inactivation of antioxidant enzymes such as ICDH and SOD. Upon exposure to 100mM ethanol for 3days to HepG2 cells, a significant decrease in the viability and activities of ICDH and SOD was observed. The ethanol-induced inactivation of antioxidant enzymes resulted in the cellular oxidative damage and modulation of redox status as well as mitochondrial dysfunction in HepG2 cells. The cytoxicity of ethanol and inactivation of antioxidant enzymes were effectively protected by manganeses(III) tetrakis(N-methyl-2-pyridyl) porphyrin, a manganese SOD mimetic, and N...Continue Reading

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Citations

Oct 1, 2011·Asian Pacific Journal of Tropical Biomedicine·T ThirumalaiE David
Feb 9, 2012·Journal of Proteome Research·Kristofer S FritzDennis R Petersen
Dec 7, 2010·Antioxidants & Redox Signaling·E Matthew MorrisJamal A Ibdah
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Jun 2, 2010·Journal of the National Cancer Institute·Zachary J Reitman, Hai Yan
Feb 27, 2015·World Journal of Biological Chemistry·Ji Yeon KimWon-Ho Kim

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