title: Attenuated mitochondrial NADP+-dependent isocitrate dehydrogenase activity induces apoptosis and hypertrophy of H9c2 cardiomyocytes.
abstract: Oxidative stress, characterized by the accumulation of reactive oxygen species (ROS), is known to have numerous detrimental effects on the myocardium such as the induction of apoptotic cell death, hypertrophy, fibrosis, dysfunction, and dilatation. Over the past several years, we have shown that mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) functions as an antioxidant and anti-apoptotic protein by supplying NADPH to antioxidant systems. Here, we showed that transfection of H9c2 clonal myoblastic cells with small interfering RNA (siRNA) specific for IDPm markedly attenuated IDPm expression and substantially induced apoptosis, senescence, and hypertrophy as indicated by increased atrial natriuretic peptide (ANP) gene expression, a marker of cardiomyocyte hypertrophy, and a larger cell size. Knockdown of IDPm expression resulted in the modulation of cellular and mitochondrial redox status, mitochondrial function, and cellular oxidative damage. Taken together, our results suggest that the suppression of IDPm expression by siRNA induces apoptosis and hypertrophy of cultured cardiomyocytes through the disruption of cellular redox balance.
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, South Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, South Korea. Electronic address: parkjw@knu.ac.kr.
authors.forename: Jeen-Woo
authors.initials: JW
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D016922:Cellular Senescence; D055785:Gene Knockdown Techniques; D006984:Hypertrophy; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D010084:Oxidation-Reduction; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats
chemical_list: D034741:RNA, Small Interfering; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+)
keywords: Apoptosis; Cardiomyocytes; Hypertrophy; Redox status; siRNA