title: Involvement of GADD153 and cardiac ankyrin repeat protein in hypoxia-induced apoptosis of H9c2 cells.
abstract: Oxidative stress is the main cause of cardiac injury during ischemia/reperfusion but the molecular mechanism for this process is unclear. In this study, it was found that hypoxia induces apoptosis in rat embryonic heart-derived H9c2 cells leading to the induction of GADD153, which is an apoptosis-related gene. Therefore, this study addressed the molecular role of GADD153 in hypoxia-induced apoptosis. The stable or inducible overexpression of GADD153 sensitized the H9c2 cells to apoptotic cell death. The results suggest that the transactivation domain of the GADD153 might be responsible for this cell execution and play a role in the nucleoplasmic localization of GADD153. The cells transiently transfected with the antisense GADD153 were more resistant to hypoxia-induced apoptosis than the vector control cells. Furthermore, GADD153 transcriptionally down-regulated the expression of the cardiac ankyrin repeat protein gene (CARP), which is a nuclear transcriptional co-factor that negatively regulates the expression of the cardiac gene. The ectopic expression of CARP in H9c2 cells increased the resistance to hypoxia-induced apoptosis. These results suggest that GADD153 overexpression and the concomitant down-regulation of CARP might have a causative role in the apoptotic cell injury of hypoxic H9c2 cells.
authors.affiliation: Division of Hepatology, Department of Internal Medicine, the Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
authors.forename: Xue-Ji
authors.initials: XJ
authors.lastname: Han
authors.forename: Jei-Keon
authors.initials: JK
authors.lastname: Chae
authors.forename: Mi-Jin
authors.initials: MJ
authors.lastname: Lee
authors.forename: Kyung-Ran
authors.initials: KR
authors.lastname: You
authors.forename: Byung-Ho
authors.initials: BH
authors.lastname: Lee
authors.forename: Dae-Ghon
authors.initials: DG
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D022762:CCAAT-Enhancer-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology*; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D009124:Muscle Proteins; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D012097:Repressor Proteins; D051742:Transcription Factor CHOP; D015533:Transcriptional Activation
chemical_list: C491303:Ankrd1 protein, rat; D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D051742:Transcription Factor CHOP