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KMID : 0620920090410040243
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Experimental & Molecular Medicine
2009 Volume.41 No. 4 p.243 ~ p.252
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Involvement of GADD153 and cardiac ankyrin repeat protein in cardiac ischemia-reperfusion injury
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Lee Mi-Jin
Kwak Yong-Keun
You Kyung-Ran
Lee Byung-Ho
Kim Dae-Ghon
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Abstract
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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.
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KEYWORD
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ANKRD1 protein, human, apoptosis, heart, reperfusion injury, transcription factor CHOP
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