Tanshinone IIA protects H9c2 cells from oxidative stress-induced cell death via microRNA-133 upregulation and Akt activation

Gu,Yunfei; Liang,Zhuo; Wang,Haijun; Jin,Jun; Zhang,Shouyan; Xue,Shufeng; Chen,Jianfeng; He,Huijuan; Duan,Kadan; Wang,Jing; Chang,Xuewei; Qiu,Chunguang

doi:10.3892/etm.2016.3400

Tanshinone IIA protects H9c2 cells from oxidative stress-induced cell death via microRNA-133 upregulation and Akt activation

Authors:
- Yunfei Gu
- Zhuo Liang
- Haijun Wang
- Jun Jin
- Shouyan Zhang
- Shufeng Xue
- Jianfeng Chen
- Huijuan He
- Kadan Duan
- Jing Wang
- Xuewei Chang
- Chunguang Qiu
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Affiliations: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Cardiology, The General Hospital of People's Liberation Army, Beijing 100853, P.R. China, Department of Cardiology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471009, P.R. China
Published online on: May 26, 2016 https://doi.org/10.3892/etm.2016.3400
Pages: 1147-1152

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Abstract

The aim of the present study was to investigate the cardioprotective effect of tanshinone IIA and the underlying molecular mechanisms. An in vitro model of oxidative stress injury was established in cardiac H9c2 cells, and the effects of tanshinone IIa were investigated using cell viability, reverse transcription‑quantitative polymerase chain reaction and western blotting assays. The results demonstrated that tanshinone IIA protects H9c2 cells from H2O2‑induced cell death in a concentration‑dependent manner, via a mechanism involving microRNA-133 (miR-133), and that treatment with TIIA alone exerted no cytotoxic effects on H9c2. In order to further elucidate the mechanisms underlying the actions of TIIA, reverse transcription‑quantitative polymease chain reaction and western blot analysis were performed. Reductions in miR‑133 expression levels induced by increasing concentrations of H2O2 were reversed by treatment with tanshinone IIA. In addition, the inhibition of miR‑133 by transfection with an miR‑133 inhibitor abolished the cardioprotective effects of tanshinone IIA against H2O2‑induced cell death. Furthermore, western blot analysis demonstrated that tanshinone IIA activated Akt kinase via the phosphorylation of serine 473. Inhibition of the phosphatidylinositol 3‑kinase (PI3K)/Akt signaling pathway by pretreatment with the PI3K specific inhibitors wortmannin and LY294002 also eliminated the cardioprotective effects of tanshinone IIA against H2O2‑induced cell death. Western blot analysis demonstrated that H2O2‑induced reductions in B cell lymphoma 2 (Bcl‑2) expression levels were reversed by tanshinone IIA. In addition, the effect of tanshinone IIA on Bcl‑2 protein expression level in an oxidative environment was suppressed by a PI3K inhibitor, wortmannin, indicating that tanshinone IIA exerts cardioprotective effects against H2O2‑induced cell death via the activation of the PI3K/Akt signal transduction pathway and the consequent upregulation of Bcl‑2. In conclusion, the present study demonstrates that TIIA is able to protcet H9c2 cells from oxidative stress‑induced cell death through signalling pathways involving miR‑133 and Akt, and that tanshinone IIA is a promising natural cardioprotective agent.

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