Cardioprotective effects of constitutively active MEK1 against H2O2-induced apoptosis and autophagy in cardiomyocytes via the ERK1/2 signaling pathway.
Biochem Biophys Res Commun
; 512(1): 125-130, 2019 04 23.
Article
em En
| MEDLINE
| ID: mdl-30876692
ABSTRACT
Oxidative stress injury is one of the main mechanisms of ischemia-reperfusion (I/R) injury. The extracellular signal-regulated kinase (ERK1/2) pathway plays an important role in cardioprotective during acute myocardial infarction. In this study, we used constitutively active MEK1 gene (CaMEK) transfection strategy to investigate whether CaMEK provides a protective effect against apoptosis and autophagy induced by Hydrogen peroxide (H2O2) in neonatal rat cardiac ventricular cardiomyocytes (NCMs) and the underlying mechanisms. As a result, CaMEK attenuated H2O2-induced apoptosis and cytotoxicity in NCMs, evidenced by decreased apoptotic cells and the ratio of Bax/Bcl-2, increased the mitochondrial membrane potential (Δψm) and cell vitality and reduced the level of lactate dehydrogenase (LDH). Further studies revealed that CaMEK attenuated H2O2-induced autophagy, evidenced by the decreased LC3-â
¡/LC3-â
ratio and SQSTM1/p62 (p62) degradation. Furthermore, we demonstrated that CaMEK phosphorylated the ERK1/2 pathway-related proteins, ERK1/2, p70S6K and GSK3ß, in NCMs with H2O2 stimulation. In contrast, these effects could be reversed by co-treatment with the ERK1/2 inhibitor, PD98059. These results suggest that CaMEK plays an important role in protecting cardiomyocytes against H2O2-induced injury and autophagy in NCMs via ERK1/2 pathway. Therefore, transfection of CaMEK may provide a hopeful therapeutic strategy for I/R.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Miócitos Cardíacos
/
MAP Quinase Quinase 1
Limite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2019
Tipo de documento:
Article