MicroRNA-21 protects against cardiac hypoxia/reoxygenation injury by inhibiting excessive autophagy in H9c2 cells via the Akt/mTOR pathway.
J Cell Mol Med
; 21(3): 467-474, 2017 03.
Article
em En
| MEDLINE
| ID: mdl-27680680
ABSTRACT
MicroRNAs and autophagy play critical roles in cardiac hypoxia/reoxygenation (H/R)-induced injury. Here, we investigated the function of miR-21 in regulating autophagy and identified the potential molecular mechanisms involved. To determine the role of miR-21 in regulating autophagy, H9c2 cells were divided into the following six groups control group, H/R group, (miR-21+ H/R) group, (miR-21-negative control + H/R) group, (BEZ235+ H/R) group and (miR-21+ BEZ235+ H/R) group. The cells underwent hypoxia for 1 hr and reoxygenation for 3 hrs. Cell count kit-8 was used to evaluate cell function and apoptosis was analysed by Western blotting. Western blotting and transmission electron microscopy were used to investigate autophagy. We found that miR-21 expression was down-regulated, and autophagy was remarkably increased in H9c2 cells during H/R injury. Overexpression of miR-21 with a miR-21 precursor significantly inhibited autophagic activity and decreased apoptosis, accompanied by the activation of the AKT/mTOR pathway. In addition, treatment with BEZ235, a novel dual Akt/mTOR inhibitor, resulted in a significant increase in autophagy and apoptosis. However, we found that miR-21-mediated inhibition of apoptosis and autophagy was partly independent of Akt/mTOR activation, as demonstrated in cells treated with both miR-21 and BEZ235. We showed that miR-21 could inhibit H/R-induced autophagy and apoptosis, which may be at least partially mediated by the Akt/mTOR signalling pathway.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Hipóxia Celular
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Miócitos Cardíacos
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MicroRNAs
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Proteínas Proto-Oncogênicas c-akt
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Serina-Treonina Quinases TOR
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article