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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2016
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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. |
format | Online Article Text |
id | pubmed-4813131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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