title: Tanshinone IIA protects H9c2 cells from oxidative stress-induced cell death via microRNA-133 upregulation and Akt activation.
abstract: The aim of the present study was to investigate the cardioprotective effect of tanshinone IIA and the underlying molecular mechanisms. Anin vitromodel 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 H2O2were 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.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China; Department of Cardiology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471009, P.R. China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Cardiology, The General Hospital of People's Liberation Army, Beijing 100853, P.R. China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Cardiology, The General Hospital of People's Liberation Army, Beijing 100853, P.R. China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471009, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Cardiology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471009, P.R. China.
authors.forename: Shouyan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471009, P.R. China.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Xue
authors.affiliation: Department of Cardiology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471009, P.R. China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471009, P.R. China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Cardiology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471009, P.R. China.
authors.forename: Kadan
authors.initials: K
authors.lastname: Duan
authors.affiliation: Department of Cardiology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471009, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471009, P.R. China.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Qiu
keywords: Akt kinase; B cell lymphoma-2; cardioprotective effect; miR-133; tanshinone IIA