Open AccessMicro RNA ‐21 protects against cardiac hypoxia/reoxygenation injury by inhibiting excessive autophagy in H9c2 cells via the Akt/ mTOR pathway
Author(s) -
Huang Zhouqing,
Wu Shengjie,
Kong Fanqi,
Cai Xueli,
Ye Bozhi,
Shan Peiren,
Huang Weijian
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12990
Subject(s) - autophagy , pi3k/akt/mtor pathway , apoptosis , protein kinase b , blot , chemistry , hypoxia (environmental) , microbiology and biotechnology , biology , biochemistry , gene , organic chemistry , oxygen
Micro RNA s 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, ( BEZ 235+ H/R) group and (miR‐21+ BEZ 235+ 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 BEZ 235, 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 BEZ 235. 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.