title: Inactivation of mitochondrial NADP+-dependent isocitrate dehydrogenase by hypochlorous acid.
abstract: Myeoloperoxidase catalyses the formation of hypochlorous acid (HOCl) via reaction of H(2)O(2) with Cl(-) ion. Although HOCl is known to play a major role in the human immune system by killing bacteria and other invading pathogens, excessive generation of this oxidant is known to cause damage to tissue. Recently, it was demonstrated that the control of mitochondrial redox balance and oxidative damage is one of the primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) to supply NADPH for antioxidant systems. This study investigated whether the IDPm would be a vulnerable target of HOCl as a purified enzyme and in intact cells. Loss of enzyme activity was observed and the inactivation of IDPm was reversed by thiols. Transfection of HeLa cells with an IDPm small interfering RNA (siRNA) markedly enhanced HOCl-induced oxidative damage to cells. The HOCl-mediated damage to IDPm may result in the perturbation of the cellular antioxidant defense mechanisms and subsequently lead to a pro-oxidant condition.
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu, South Korea.
authors.forename: Sin Young
authors.initials: SY
authors.lastname: Park
authors.forename: Su-Min
authors.initials: SM
authors.lastname: Lee
authors.forename: Seoung Woo
authors.initials: SW
authors.lastname: Shin
authors.forename: Jeen-Woo
authors.initials: JW
authors.lastname: Park
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000494:pharmacology*; D007521:Isocitrate Dehydrogenase / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D034741:RNA, Small Interfering / Q000378:metabolism; D013552:Swine
chemical_list: D000975:Antioxidants; D034741:RNA, Small Interfering; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D007521:Isocitrate Dehydrogenase