title: Involvement of GADD153 and cardiac ankyrin repeat protein in cardiac ischemia-reperfusion injury.
abstract: Oxidative stress is critical for causing cardiac injuries during ischemia-reperfusion (IR), yet the molecular mechanism for this remains unclear. In the present study, we observe that hypoxia and reoxygenation, a component of ischemia, effectively induces apoptosis in the cardiac myocytes from neonatal rats and it concomitantly leads to induction of GADD153, an apoptosis-related gene. Furthermore, IR injury of rat heart showed a GADD153 overexpression in the ischemic area where the TUNEL reaction was positive. A downregulation of cardiac ankyrin repeat protein (CARP) was also observed in this ischemic area. Promoter deletion and reporter analysis revealed that hypoxia transcriptionally activates a GADD153 promoter through the AP-1 element in neonatal cardiomyocytes. Ectopic overexpression of GADD153 resulted in the downregulation of CARP expression. Accordingly, the induction of GADD153 mRNA were followed by the CARP down-regulation in an in vivo rat coronary ischemia/reperfusion injury model. These results suggest that GADD153 over-expression and the resulting downregulation of CARP may have causative roles in apoptotic cell death during cardiac IR injury.
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School and Hospital, Jeonju 561-712, Korea.
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Lee
authors.forename: Yong Keun
authors.initials: YK
authors.lastname: Kwak
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; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D000860:Hypoxia; D008297:Male; D009124:Muscle Proteins; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism*
chemical_list: C491303:Ankrd1 protein, rat; C497251:Ddit3 protein, rat; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; D051742:Transcription Factor CHOP