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Regulation of ethanol-induced toxicity by mitochondrial NADP(+)-dependent isocitrate dehydrogenase.
Biochimie. 2009 Aug; 91(8):1020-8.B

Abstract

Chronic alcohol administration has been known to increase peroxynitrite hepatotoxicity by enhancing concomitant production of nitric oxide and superoxide. We previously reported that control of the mitochondrial redox balance and the cellular defense against oxidative damage are primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) through to supply NADPH for antioxidant systems. In the present study, we demonstrate that modulation of IDPm expression in HepG2 cells regulates ethanol-induced toxicity. We observed the significantly enhanced protection to cell killing, lipid peroxidation, protein oxidation, oxidative DNA damage, and decrease in generation of intracellular reactive oxygen species and reactive nitrogen species in IDPm-overexpressed cells compared to control cells upon exposure to ethanol. In contrast, transfection of HepG2 cells with IDPm short interfering RNA markedly decreased the expression of IDPm, modulating cellular redox status and subsequently enhancing the susceptibility of ethanol-induced toxicity. These studies support the hypothesis that IDPm plays an important role in regulating the toxicity induced by ethanol presumably through maintaining the cellular redox status.

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Publisher Full Text

Authors+Show Affiliations

Yang ES
Kyungpook National University, Taegu, Republic of Korea.
Park JW
No affiliation info available

MeSH

Amino Acid SequenceAntioxidantsCell Line, TumorCytochrome P-450 CYP2E1DNA, ComplementaryEthanolGene Expression Regulation, EnzymologicGene Knockdown TechniquesHumansIsocitrate DehydrogenaseMitochondriaMolecular Sequence DataOxidation-ReductionOxidative StressPeroxynitrous AcidRNA, Small InterferingTransfection

Pub Type(s)

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

Language

eng

PubMed ID

19500645

Citation

Yang, Eun Sun, and Jeen-Woo Park. "Regulation of Ethanol-induced Toxicity By Mitochondrial NADP(+)-dependent Isocitrate Dehydrogenase." Biochimie, vol. 91, no. 8, 2009, pp. 1020-8.
Yang ES, Park JW. Regulation of ethanol-induced toxicity by mitochondrial NADP(+)-dependent isocitrate dehydrogenase. Biochimie. 2009;91(8):1020-8.
Yang, E. S., & Park, J. W. (2009). Regulation of ethanol-induced toxicity by mitochondrial NADP(+)-dependent isocitrate dehydrogenase. Biochimie, 91(8), 1020-8. https://doi.org/10.1016/j.biochi.2009.05.008
Yang ES, Park JW. Regulation of Ethanol-induced Toxicity By Mitochondrial NADP(+)-dependent Isocitrate Dehydrogenase. Biochimie. 2009;91(8):1020-8. PubMed PMID: 19500645.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of ethanol-induced toxicity by mitochondrial NADP(+)-dependent isocitrate dehydrogenase. AU - Yang,Eun Sun, AU - Park,Jeen-Woo, Y1 - 2009/06/12/ PY - 2008/10/29/received PY - 2009/05/20/accepted PY - 2009/6/9/entrez PY - 2009/6/9/pubmed PY - 2009/10/14/medline SP - 1020 EP - 8 JF - Biochimie JO - Biochimie VL - 91 IS - 8 N2 - Chronic alcohol administration has been known to increase peroxynitrite hepatotoxicity by enhancing concomitant production of nitric oxide and superoxide. We previously reported that control of the mitochondrial redox balance and the cellular defense against oxidative damage are primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) through to supply NADPH for antioxidant systems. In the present study, we demonstrate that modulation of IDPm expression in HepG2 cells regulates ethanol-induced toxicity. We observed the significantly enhanced protection to cell killing, lipid peroxidation, protein oxidation, oxidative DNA damage, and decrease in generation of intracellular reactive oxygen species and reactive nitrogen species in IDPm-overexpressed cells compared to control cells upon exposure to ethanol. In contrast, transfection of HepG2 cells with IDPm short interfering RNA markedly decreased the expression of IDPm, modulating cellular redox status and subsequently enhancing the susceptibility of ethanol-induced toxicity. These studies support the hypothesis that IDPm plays an important role in regulating the toxicity induced by ethanol presumably through maintaining the cellular redox status. SN - 1638-6183 UR - https://www.unboundmedicine.com/medline/citation/19500645/Regulation_of_ethanol_induced_toxicity_by_mitochondrial_NADP_+__dependent_isocitrate_dehydrogenase_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-9084(09)00150-3 DB - PRIME DP - Unbound Medicine ER -