Eur Rev Med Pharmacol Sci 2018; 22 (18): 6109-6118

DOI: 10.26355/eurrev_201809_15950

Down-regulation of miR-192 protects against rat ischemia-reperfusion injury after myocardial infarction

J. Dong, Y. Zhao, X.-K. He

Department of Three Cardiovascular Ward, The Second Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, China. bayanconglinlu@163.com


OBJECTIVE: DJ-1-phosphate and tension homology deleted on chromosome ten/phosphatidylinositol-3-kinase/protein kinase B (PTEN/PI3K/AKT) signaling pathway plays a role in the regulation of ischemic reperfusion (I-R) injury. Bioinformatics analysis demonstrated that there is a complementary binding site between microRNA-192 (miR-192) and the 3’-UTR of DJ-1 mRNA. This study investigated the role of miR-192 in regulating DJ-1-PTEN/PI3K/AKT signaling pathway and myocardial I-R injury.

MATERIALS AND METHODS: miR-122 and DJ-1 mRNA expressions in myocardial tissue were detected by Real-time PCR (RT-PCR). DJ-1, PTEN, and phosphorylated AKT (p-AKT) protein expressions were tested by Western blot. Reactive oxygen species (ROS) content was measured by flow cytometry. Malondialdehyde (MDA) content and superoxide dismutase (SOD) enzyme activity were detected by the kits. I-R treatment was performed at 72 h after transfection. Cell apoptosis was evaluated with flow cytometry.

RESULTS: Compared with sham group, miR-192, PTEN expressions and MDA content were significantly increased (p<0.05), while DJ-1, p-AKT levels and SOD activities were significantly reduced (p<0.05) in myocardial tissue of I-R group. Compared with control, I-R treatment significantly up-regulated miR-192 level, significantly decreased DJ-1 and p-AKT proteins, significantly elevated PTEN expression, and significantly induced apoptosis and ROS production in H9C2 cells (p<0.05). Transfection of miR-192 inhibitor significantly enhanced DJ-1 level, declined PTEN expression, elevated p-AKT level, and restrained apoptosis, ROS production and MDA content, and promoted SOD activity in H9C2 cells under I-R condition.

CONCLUSIONS: The expression of miR-192 increased significantly, while the expression of DJ-1 reduced obviously during I-R injury after myocardial infarction. Down-regulation of miR-192 markedly enhanced DJ-1 expression and PTEN/PI3K/AKT pathway activity, inhibited cell apoptosis and ROS generation, and reduced I-R injury in cardiomyocytes.

Free PDF Download

To cite this article

J. Dong, Y. Zhao, X.-K. He
Down-regulation of miR-192 protects against rat ischemia-reperfusion injury after myocardial infarction

Eur Rev Med Pharmacol Sci
Year: 2018
Vol. 22 - N. 18
Pages: 6109-6118
DOI: 10.26355/eurrev_201809_15950