Involvement of GADD153 and cardiac ankyrin repeat protein in cardiac ischemia-reperfusion injury

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 neona...

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Bibliographic Details
Published in:Experimental & molecular medicine 2009, 41(4), , pp.243-252
Main Authors: Lee, Mi-Jin, Kwak, Yong-Keun, You, Kyung-Ran, Lee, Byung-Ho, Kim, Dae-Ghon
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Apoptosis - physiology
Biomedical and Life Sciences
Biomedicine
Cells, Cultured
Humans
Hypoxia
Male
Medical Biochemistry
Molecular Medicine
Muscle Proteins
Myocardial Reperfusion Injury - metabolism
Myocardial Reperfusion Injury - pathology
Myocardium - metabolism
Myocardium - pathology
Myocytes, Cardiac - cytology
Myocytes, Cardiac - metabolism
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Original
Promoter Regions, Genetic
Rats
Rats, Sprague-Dawley
Repressor Proteins - genetics
Repressor Proteins - metabolism
Stem Cells
Transcription Factor AP-1 - genetics
Transcription Factor AP-1 - metabolism
Transcription Factor CHOP - genetics
Transcription Factor CHOP - metabolism
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Summary: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.
ISSN:1226-3613
2092-6413
DOI:10.3858/emm.2009.41.4.027