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The Protective Role of the TOPK/PBK Pathway in Myocardial Ischemia/Reperfusion and H(2)O(2)-Induced Injury in H9C2 Cardiomyocytes

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 unclea...

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Autores principales: Sun, Guozhe, Ye, Ning, Dai, Dongxue, Chen, Yintao, Li, Chao, Sun, Yingxian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813131/
https://www.ncbi.nlm.nih.gov/pubmed/26907268
http://dx.doi.org/10.3390/ijms17030267
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author Sun, Guozhe
Ye, Ning
Dai, Dongxue
Chen, Yintao
Li, Chao
Sun, Yingxian
author_facet Sun, Guozhe
Ye, Ning
Dai, Dongxue
Chen, Yintao
Li, Chao
Sun, Yingxian
author_sort Sun, Guozhe
collection PubMed
description 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 (H(2)O(2)) 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, H(2)O(2) induced TOPK phosphorylation in a time-dependent manner. Interestingly, TOPK inhibition aggravated the H(2)O(2)-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.
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spelling pubmed-48131312016-04-06 The Protective Role of the TOPK/PBK Pathway in Myocardial Ischemia/Reperfusion and H(2)O(2)-Induced Injury in H9C2 Cardiomyocytes Sun, Guozhe Ye, Ning Dai, Dongxue Chen, Yintao Li, Chao Sun, Yingxian Int J Mol Sci Article 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 (H(2)O(2)) 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, H(2)O(2) induced TOPK phosphorylation in a time-dependent manner. Interestingly, TOPK inhibition aggravated the H(2)O(2)-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. MDPI 2016-02-23 /pmc/articles/PMC4813131/ /pubmed/26907268 http://dx.doi.org/10.3390/ijms17030267 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sun, Guozhe
Ye, Ning
Dai, Dongxue
Chen, Yintao
Li, Chao
Sun, Yingxian
The Protective Role of the TOPK/PBK Pathway in Myocardial Ischemia/Reperfusion and H(2)O(2)-Induced Injury in H9C2 Cardiomyocytes
title The Protective Role of the TOPK/PBK Pathway in Myocardial Ischemia/Reperfusion and H(2)O(2)-Induced Injury in H9C2 Cardiomyocytes
title_full The Protective Role of the TOPK/PBK Pathway in Myocardial Ischemia/Reperfusion and H(2)O(2)-Induced Injury in H9C2 Cardiomyocytes
title_fullStr The Protective Role of the TOPK/PBK Pathway in Myocardial Ischemia/Reperfusion and H(2)O(2)-Induced Injury in H9C2 Cardiomyocytes
title_full_unstemmed The Protective Role of the TOPK/PBK Pathway in Myocardial Ischemia/Reperfusion and H(2)O(2)-Induced Injury in H9C2 Cardiomyocytes
title_short The Protective Role of the TOPK/PBK Pathway in Myocardial Ischemia/Reperfusion and H(2)O(2)-Induced Injury in H9C2 Cardiomyocytes
title_sort protective role of the topk/pbk pathway in myocardial ischemia/reperfusion and h(2)o(2)-induced injury in h9c2 cardiomyocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813131/
https://www.ncbi.nlm.nih.gov/pubmed/26907268
http://dx.doi.org/10.3390/ijms17030267
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