Involvement of GADD153 and cardiac ankyrin repeat protein in cardiac ischemia-reperfusion injury
Experimental & Molecular Medicine
;
: 243-252, 2009.
Article
Dans Anglais
| 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.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Protéines de répression
/
Protéines nucléaires
/
Lésion de reperfusion myocardique
/
Cellules cultivées
/
Régions promotrices (génétique)
/
Rat Sprague-Dawley
/
Apoptose
/
Facteur de transcription AP-1
/
Myocytes cardiaques
/
Facteur de transcription CHOP
Type d'étude:
Étude pronostique
Limites du sujet:
Animaux
/
Humains
/
Mâle
langue:
Anglais
Texte intégral:
Experimental & Molecular Medicine
Année:
2009
Type:
Article
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