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
  • View Affiliations

  • Published online on: May 26, 2016     https://doi.org/10.3892/etm.2016.3400
  • Pages: 1147-1152
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.
View Figures
View References

Related Articles

Journal Cover

August-2016
Volume 12 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Gu Y, Liang Z, Wang H, Jin J, Zhang S, Xue S, Chen J, He H, Duan K, Wang J, Wang J, et al: Tanshinone IIA protects H9c2 cells from oxidative stress-induced cell death via microRNA-133 upregulation and Akt activation. Exp Ther Med 12: 1147-1152, 2016.
APA
Gu, Y., Liang, Z., Wang, H., Jin, J., Zhang, S., Xue, S. ... Qiu, C. (2016). Tanshinone IIA protects H9c2 cells from oxidative stress-induced cell death via microRNA-133 upregulation and Akt activation. Experimental and Therapeutic Medicine, 12, 1147-1152. https://doi.org/10.3892/etm.2016.3400
MLA
Gu, Y., Liang, Z., Wang, H., Jin, J., Zhang, S., Xue, S., Chen, J., He, H., Duan, K., Wang, J., Chang, X., Qiu, C."Tanshinone IIA protects H9c2 cells from oxidative stress-induced cell death via microRNA-133 upregulation and Akt activation". Experimental and Therapeutic Medicine 12.2 (2016): 1147-1152.
Chicago
Gu, Y., Liang, Z., Wang, H., Jin, J., Zhang, S., Xue, S., Chen, J., He, H., Duan, K., Wang, J., Chang, X., Qiu, C."Tanshinone IIA protects H9c2 cells from oxidative stress-induced cell death via microRNA-133 upregulation and Akt activation". Experimental and Therapeutic Medicine 12, no. 2 (2016): 1147-1152. https://doi.org/10.3892/etm.2016.3400