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Int. J. Mol. Sci. 2016, 17(3), 267; doi:10.3390/ijms17030267

The Protective Role of the TOPK/PBK Pathway in Myocardial Ischemia/Reperfusion and H2O2-Induced Injury in H9C2 Cardiomyocytes

1
Department of Cardiovascular Medicine, the First Hospital of China Medical University, Shenyang 110001, Liaoning, China
2
Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110122, Liaoning, China
*
Author to whom correspondence should be addressed.
Academic Editors: H. W. M. Niessen and Paul A. J. Krijnen
Received: 14 December 2015 / Revised: 5 February 2016 / Accepted: 17 February 2016 / Published: 23 February 2016
(This article belongs to the Special Issue Improvement of Cardiac Function in Heart Failure)
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Abstract

T-LAK-cell-originated protein kinase (TOPK) is a PDZ-binding kinase (PBK) that was recently identified as a novel member of the mitogen-activated protein kinase (MAPK) family. It has been shown to play an important role in many cellular functions. However, its role in cardiac function remains unclear. Thus, we have herein explored the biological function of TOPK in myocardial ischemia/reperfusion (I/R) and oxidative stress injury in H9C2 cardiomyocytes. I/R and ischemic preconditioning (IPC) were induced in rats by 3-hour reperfusion after 30-min occlusion of the left anterior descending coronary artery and by 3 cycles of 5-min I/R. Hydrogen peroxide (H2O2) was used to induce oxidative stress in H9C2 cardiomyocytes. TOPK expression was analyzed by western blotting, RT-PCR, immunohistochemical staining, and immunofluorescence imaging studies. The effects of TOPK gene overexpression and its inhibition via its inhibitor HI-TOPK-032 on cell viability and Bcl-2, Bax, ERK1/2, and p-ERK1/2 protein expression were analyzed by MTS assay and western blotting, respectively. The results showed that IPC alleviated myocardial I/R injury and induced TOPK activation. Furthermore, H2O2 induced TOPK phosphorylation in a time-dependent manner. Interestingly, TOPK inhibition aggravated the H2O2-induced oxidative stress injury in myocardiocytes, whereas overexpression relieved it. In addition, the ERK pathway was positively regulated by TOPK signaling. In conclusion, our results indicate that TOPK might mediate a novel survival signal in myocardial I/R, and that its effect on anti-oxidative stress involves the ERK signaling pathway. View Full-Text
Keywords: ischemia/reperfusion; ischemic preconditioning; oxidative stress; TOPK/PBK ischemia/reperfusion; ischemic preconditioning; oxidative stress; TOPK/PBK
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MDPI and ACS Style

Sun, G.; Ye, N.; Dai, D.; Chen, Y.; Li, C.; Sun, Y. The Protective Role of the TOPK/PBK Pathway in Myocardial Ischemia/Reperfusion and H2O2-Induced Injury in H9C2 Cardiomyocytes. Int. J. Mol. Sci. 2016, 17, 267.

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