MiR-28 inhibits cardiomyocyte survival through suppressing PDK1/Akt/mTOR signaling

被引:0
作者
Rui-Yao Zhu
Di Zhang
Han-Dong Zou
Xiao-Shu Zuo
Qing-Shan Zhou
He Huang
机构
[1] Renmin Hospital of Wuhan University,Department of Critical Care Medicine
[2] Renmin Hospital of Wuhan University,Department of Cardiology
[3] Hubei Key Laboratory of Cardiology,undefined
来源
In Vitro Cellular & Developmental Biology - Animal | 2016年 / 52卷
关键词
Heart; Apoptosis; MicroRNA; Akt; mTOR;
D O I
暂无
中图分类号
学科分类号
摘要
MicroRNAs play critical roles in regulating cell survival under multiple pathological conditions of heart diseases. Oxidative stress-induced apoptosis contributes greatly to heart ischemia-reperfusion injury. Herein, we describe a novel regulatory role of miR-28 on the survival of cardiomyocytes. We show that miR-28 was upregulated in cardiomyocytes treated with hydrogen peroxide (H2O2). MiR-28 gain of function sensitized cell apoptosis, whereas miR-28 loss of function partially rescued cell apoptosis induced by H2O2. Importantly, we observed a significant reduction in Akt/mammalian target of rapamycin (mTOR) signaling activity after miR-28 treatment. Luciferase activity assay and western blot analysis both revealed that, phosphoinositide-dependent kinase-1 (PDK1), which is critical for Akt activation, was directly and negatively modulated by miR-28. Our results therefore indicate that miR-28 regulates oxidative stress-induced cell apoptosis in heart muscle cells, which possibly involves a PDK1/Akt/mTOR-dependent mechanism. MIR-28 could serve as a critical therapeutic target to diminish oxidative stress-induced cell death in the heart.
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页码:1020 / 1025
页数:5
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