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Ethanol induces peroxynitrite-mediated toxicity through inactivation of NADP+-dependent isocitrate dehydrogenase and superoxide dismutase.
Biochimie. 2008 Sep; 90(9):1316-24.B

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'-monomethyl-l-arginine, a nitric oxide synthase inhibitor. These results indicate that ethanol toxicity is mediated by peroxynitrite and the peroxynitrite-mediated damage to ICDH and SOD may be resulted in the perturbation of the cellular antioxidant defense systems and subsequently lead to a pro-oxidant condition.

Authors+Show Affiliations

School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, 1370 Sankyuk-Dong, Taegu 702-701, Korea.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18405671

Citation

Yang, Eun Sun, et al. "Ethanol Induces Peroxynitrite-mediated Toxicity Through Inactivation of NADP+-dependent Isocitrate Dehydrogenase and Superoxide Dismutase." Biochimie, vol. 90, no. 9, 2008, pp. 1316-24.
Yang ES, Lee JH, Park JW. Ethanol induces peroxynitrite-mediated toxicity through inactivation of NADP+-dependent isocitrate dehydrogenase and superoxide dismutase. Biochimie. 2008;90(9):1316-24.
Yang, E. S., Lee, J. H., & Park, J. W. (2008). Ethanol induces peroxynitrite-mediated toxicity through inactivation of NADP+-dependent isocitrate dehydrogenase and superoxide dismutase. Biochimie, 90(9), 1316-24. https://doi.org/10.1016/j.biochi.2008.03.001
Yang ES, Lee JH, Park JW. Ethanol Induces Peroxynitrite-mediated Toxicity Through Inactivation of NADP+-dependent Isocitrate Dehydrogenase and Superoxide Dismutase. Biochimie. 2008;90(9):1316-24. PubMed PMID: 18405671.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ethanol induces peroxynitrite-mediated toxicity through inactivation of NADP+-dependent isocitrate dehydrogenase and superoxide dismutase. AU - Yang,Eun Sun, AU - Lee,Jin Hyup, AU - Park,Jeen-Woo, Y1 - 2008/03/19/ PY - 2007/12/07/received PY - 2008/03/10/accepted PY - 2008/4/15/pubmed PY - 2008/10/4/medline PY - 2008/4/15/entrez SP - 1316 EP - 24 JF - Biochimie JO - Biochimie VL - 90 IS - 9 N2 - 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'-monomethyl-l-arginine, a nitric oxide synthase inhibitor. These results indicate that ethanol toxicity is mediated by peroxynitrite and the peroxynitrite-mediated damage to ICDH and SOD may be resulted in the perturbation of the cellular antioxidant defense systems and subsequently lead to a pro-oxidant condition. SN - 0300-9084 UR - https://www.unboundmedicine.com/medline/citation/18405671/Ethanol_induces_peroxynitrite_mediated_toxicity_through_inactivation_of_NADP+_dependent_isocitrate_dehydrogenase_and_superoxide_dismutase_ DB - PRIME DP - Unbound Medicine ER -