Mitochondrial chaperone tumour necrosis factor receptor-associated protein 1 protects cardiomyocytes from hypoxic injury by regulating mitochondrial permeability transition pore opening.
FEBS J
; 277(8): 1929-38, 2010 Apr.
Article
em En
| MEDLINE
| ID: mdl-20236315
ABSTRACT
Tumour necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial chaperone that plays a role in maintaining mitochondrial function and regulating cell apoptosis. The opening of the mitochondrial permeability transition pore (MPTP) is a key step in cell death after hypoxia. However, it is still unclear whether TRAP1 protects cardiomyocytes from hypoxic damage by regulating the opening of the pore. In the present study, primary cultured cardiomyocytes from neonatal rats were used to investigate changes in TRAP1 expression after hypoxia treatment as well as the mechanism and effect of TRAP1 on hypoxic damage. The results obtained showed that TRAP1 expression increased after 1 h of hypoxia and continued to increase for up to 12 h of treatment. Hypoxia caused an increase in cell death and decreased cell viability and mitochondrial membrane potential; overexpressing TRAP1 prevented hypoxia-induced damage to cardiomyocytes. The silencing of TRAP1 induced an increase in cell death and decreased both cell viability and mitochondrial membrane potential in cardiomyocytes under normoxic and hypoxic conditions. Furthermore, cell damage induced by the silencing of TRAP1 was prevented by the mitochondrial permeability transition pore inhibitor, cyclosporin A. These data demonstrate that hypoxia induces an increase in TRAP1 expression in cardiomyocytes, and that TRAP1 plays a protective role by regulating the opening of the mitochondrial permeability transition pore.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Miócitos Cardíacos
/
Proteínas de Transporte da Membrana Mitocondrial
/
Fator 1 Associado a Receptor de TNF
/
Hipóxia
/
Mitocôndrias Cardíacas
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
FEBS J
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
China