title: Silencing of mitochondrial NADP+-dependent isocitrate dehydrogenase by small interfering RNA enhances heat shock-induced apoptosis.
abstract: Heat shock may increase oxidative stress due to increased production of reactive oxygen species and/or the promotion of cellular oxidation events. Mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) produces NADPH, an essential reducing equivalent for the antioxidant system. In this report, we demonstrate that silencing of IDPm expression in HeLa cells greatly enhances apoptosis induced by heat shock. Transfection of HeLa cells with an IDPm small interfering RNA (siRNA) markedly decreased activity of IDPm, enhancing the susceptibility of heat shock-induced apoptosis reflected by morphological evidence of apoptosis, DNA fragmentation, cellular redox status, mitochondria redox status and function, and the modulation of apoptotic marker proteins. These results indicate that IDPm may play an important role in regulating the apoptosis induced by heat shock and the sensitizing effect of IDPm siRNA on the apoptotic cell death of HeLa cells offers the possibility of developing a modifier of cancer therapy.
authors: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Republic of Korea.
authors: Seoung Woo
authors: SW
authors: Shin
authors: In Sup
authors: IS
authors: Kil
authors: Jeen-Woo
authors: JW
authors: Park
mesh_terms: D017209:Apoptosis; D020868:Gene Silencing; D006367:HeLa Cells; D018869:Heat-Shock Response; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics*; D010084:Oxidation-Reduction; D034741:RNA, Small Interfering / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+)