Involvement of GADD153 and cardiac ankyrin repeat protein in cardiac ischemia-reperfusion injury
Experimental & Molecular Medicine
;
: 243-252, 2009.
Article
in English
| WPRIM
| ID: wpr-49343
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Repressor Proteins
/
Nuclear Proteins
/
Myocardial Reperfusion Injury
/
Cells, Cultured
/
Promoter Regions, Genetic
/
Rats, Sprague-Dawley
/
Apoptosis
/
Transcription Factor AP-1
/
Myocytes, Cardiac
/
Transcription Factor CHOP
Type of study:
Prognostic study
Limits:
Animals
/
Humans
/
Male
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2009
Type:
Article
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