title: Downregulation of IDH2 exacerbates H2O2-mediated cell death and hypertrophy.
abstract: OBJECTIVE
  Reactive oxygen species-mediated cell death contributes to the pathophysiology of cardiovascular disease and myocardial dysfunction. We recently showed that mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) functions as an antioxidant and anti-apoptotic protein by supplying NADPH to antioxidant systems.
  
  
  METHODS
  In the present study, we demonstrated that H2O2-induced apoptosis and hypertrophy of H9c2 cardiomyoblasts was markedly exacerbated by small interfering RNA (siRNA) specific for IDH2.
  
  
  RESULTS
  Attenuated IDH2 expression resulted in the modulation of cellular and mitochondrial redox status, mitochondrial function, and cellular oxidative damage. MitoTEMPO, a mitochondria-targeted antioxidant, efficiently suppressed increased caspase-3 activity, increased cell size, and depletion of cellular GSH levels in IDH2 siRNA-transfected cells that were treated with H2O2.
  
  
  CONCLUSIONS
  These results indicated that the disruption of cellular redox balance might be responsible for the enhanced H2O2-induced apoptosis and hypertrophy of cultured cardiomyocytes by the attenuated IDH2 expression.
authors: a School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group , Kyungpook National University , Taegu , Korea.
authors: Hyeong Jun
authors: HJ
authors: Ku
authors: a School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group , Kyungpook National University , Taegu , Korea.
authors: Jeen-Woo
authors: JW
authors: Park
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006984:Hypertrophy / Q000378:metabolism / Q000473:pathology; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D034741:RNA, Small Interfering; D051381:Rats
chemical_list: D034741:RNA, Small Interfering; D006861:Hydrogen Peroxide; D007521:Isocitrate Dehydrogenase
keywords: Apoptosis; Cardiomyocytes; Hypertrophy; Redox status; mitoTEMPO