Journal
EXPERIMENTAL AND MOLECULAR MEDICINE
Volume 41, Issue 4, Pages 243-252Publisher
NATURE PUBLISHING GROUP
DOI: 10.3858/emm.2009.41.4.027
Keywords
ANKRD1 protein, human; apoptosis; heart; reperfusion injury; transcription factor CHOP
Funding
- Ministry of Health, Welfare and Family affairs [0620220-1]
- Ministry of Science and Technology [FG08-12-03]
- Republic of Korea
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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 down-regulation 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 down-regulation 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 down-regulation of CARP may have causative roles in apoptotic cell death during cardiac IR injury.
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