title: Silencing of mitochondrial NADP(+)-dependent isocitrate dehydrogenase gene enhances glioma radiosensitivity.
abstract: Reactive oxygen species (ROS) levels are elevated in organisms that have been exposed to ionizing radiation and are protagonists in the induction of cell death. Recently, we demonstrated that the control of mitochondrial redox balance and the cellular defense against oxidative damage are primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) via the supply of NADPH for antioxidant systems. In the present study, we report an autophagic response to ionizing radiation in A172 glioma cells transfected with small interfering RNA (siRNA) targeting the IDPm gene. Autophagy in A172 transfectant cells was associated with enhanced autophagolysosome formation and GFP-LC3 punctuation/aggregation. Furthermore, we found that the inhibition of autophagy by chloroquine augmented apoptotic cell death of irradiated A172 cells transfected with IDPm siRNA. Taken together, our data suggest that autophagy functions as a survival mechanism in A172 cells against ionizing radiation-induced apoptosis and the sensitizing effect of IDPm siRNA and autophagy inhibitor on the ionizing radiation-induced apoptotic cell death of glioma cells offers a novel redox-active therapeutic strategy for the treatment of cancer.
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu, Republic of Korea.
authors.forename: Sung Youl
authors.initials: SY
authors.lastname: Kim
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
authors.forename: Jeen-Woo
authors.initials: JW
authors.lastname: Park
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D002738:Chloroquine / Q000494:pharmacology; D005910:Glioma / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D011836:Radiation Tolerance / Q000235:genetics*; D011839:Radiation, Ionizing; D014407:Tumor Cells, Cultured
chemical_list: D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D002738:Chloroquine; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+)