Involvement of GADD153 and cardiac ankyrin repeat protein in cardiac ischemia-reperfusion injury
Experimental & Molecular Medicine
;
: 243-252, 2009.
Artigo
em Inglês
| 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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Proteínas Repressoras
/
Proteínas Nucleares
/
Traumatismo por Reperfusão Miocárdica
/
Células Cultivadas
/
Regiões Promotoras Genéticas
/
Ratos Sprague-Dawley
/
Apoptose
/
Fator de Transcrição AP-1
/
Miócitos Cardíacos
/
Fator de Transcrição CHOP
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
/
Humanos
/
Masculino
Idioma:
Inglês
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2009
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS