SRV2 promotes mitochondrial fission and Mst1-Drp1 signaling in LPS-induced septic cardiomyopathy.
Aging (Albany NY)
; 12(2): 1417-1432, 2020 01 17.
Article
em En
| MEDLINE
| ID: mdl-31951593
ABSTRACT
Mitochondrial fission is associated with cardiomyocyte death and myocardial depression, and suppressor of ras val-2 (SRV2) is a newly discovered pro-fission protein. In this study, we examined the mechanisms of SRV2-mediated mitochondrial fission in septic cardiomyopathy. Western blotting, ELISA, and immunofluorescence were used to evaluate mitochondrial function, oxidative balance, energy metabolism and caspase-related death, and siRNA and adenoviruses were used to perform loss- and gain-of-function assays. Our results demonstrated that increased SRV2 expression promotes, while SRV2 knockdown attenuates, cardiomyocyte death in LPS-induced septic cardiomyopathy. Mechanistically, SRV2 activation promoted mitochondrial fission and physiological abnormalities by upregulating oxidative injury, ATP depletion, and caspase-9-related apoptosis. Our results also demonstrated that SRV2 promotes mitochondrial fission via a Mst1-Drp1 axis. SRV2 knockdown decreased Mst1 and Drp1 levels, while Mst1 overexpression abolished the mitochondrial protection and cardiomyocyte survival-promoting effects of SRV2 knockdown. SRV2 is thus a key novel promotor of mitochondrial fission and Mst1-Drp1 axis activity in septic cardiomyopathy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas
/
Fator de Crescimento de Hepatócito
/
Proteínas Mitocondriais
/
Dinâmica Mitocondrial
/
Proteínas Quinases Associadas com Morte Celular
/
Mitocôndrias
/
Cardiomiopatias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Aging (Albany NY)
Assunto da revista:
GERIATRIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China