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Selective Inhibition of PKCβ2 Restores Ischemic Postconditioning-Mediated Cardioprotection by Modulating Autophagy in Diabetic Rats

Diabetic hearts are more susceptible to myocardial ischemia/reperfusion (I/R) injury and less sensitive to ischemic postconditioning (IPostC), but the underlying mechanisms remain unclear. PKCβ2 is preferentially overactivated in diabetic myocardium, in which autophagy status is abnormal. This study...

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Autores principales: Wang, Yafeng, Zhou, Lu, Su, Wating, Huang, Fengnan, Zhang, Yuan, Xia, Zhong-yuan, Xia, Zhengyuan, Lei, Shaoqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157806/
https://www.ncbi.nlm.nih.gov/pubmed/32337288
http://dx.doi.org/10.1155/2020/2408240
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author Wang, Yafeng
Zhou, Lu
Su, Wating
Huang, Fengnan
Zhang, Yuan
Xia, Zhong-yuan
Xia, Zhengyuan
Lei, Shaoqing
author_facet Wang, Yafeng
Zhou, Lu
Su, Wating
Huang, Fengnan
Zhang, Yuan
Xia, Zhong-yuan
Xia, Zhengyuan
Lei, Shaoqing
author_sort Wang, Yafeng
collection PubMed
description Diabetic hearts are more susceptible to myocardial ischemia/reperfusion (I/R) injury and less sensitive to ischemic postconditioning (IPostC), but the underlying mechanisms remain unclear. PKCβ2 is preferentially overactivated in diabetic myocardium, in which autophagy status is abnormal. This study determined whether hyperglycemia-induced PKCβ2 activation resulted in autophagy abnormality and compromised IPostC cardioprotection in diabetes. We found that diabetic rats showed higher cardiac PKCβ2 activation and lower autophagy than control at baseline. However, myocardial I/R further increased PKCβ2 activation and promoted autophagy status in diabetic rats. IPostC significantly attenuated postischemic infarct size and CK-MB, accompanied with decreased PKCβ2 activation and autophagy in control but not in diabetic rats. Pretreatment with CGP53353, a selective inhibitor of PKCβ2, attenuated myocardial I/R-induced infarction and autophagy and restored IPostC-mediated cardioprotection in diabetes. Similarly, CGP53353 could restore hypoxic postconditioning (HPostC) protection against hypoxia reoxygenation- (HR-) induced injury evidenced by decreased LDH release and JC-1 monomeric cells and increased cell viability. These beneficial effects of CGP53353 were reversed by autophagy inducer rapamycin, but could be mimicked by autophagy inhibitor 3-MA. It is concluded that selective inhibition of PKCβ2 could attenuate myocardial I/R injury and restore IPostC-mediated cardioprotection possibly through modulating autophagy in diabetes.
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spelling pubmed-71578062020-04-24 Selective Inhibition of PKCβ2 Restores Ischemic Postconditioning-Mediated Cardioprotection by Modulating Autophagy in Diabetic Rats Wang, Yafeng Zhou, Lu Su, Wating Huang, Fengnan Zhang, Yuan Xia, Zhong-yuan Xia, Zhengyuan Lei, Shaoqing J Diabetes Res Research Article Diabetic hearts are more susceptible to myocardial ischemia/reperfusion (I/R) injury and less sensitive to ischemic postconditioning (IPostC), but the underlying mechanisms remain unclear. PKCβ2 is preferentially overactivated in diabetic myocardium, in which autophagy status is abnormal. This study determined whether hyperglycemia-induced PKCβ2 activation resulted in autophagy abnormality and compromised IPostC cardioprotection in diabetes. We found that diabetic rats showed higher cardiac PKCβ2 activation and lower autophagy than control at baseline. However, myocardial I/R further increased PKCβ2 activation and promoted autophagy status in diabetic rats. IPostC significantly attenuated postischemic infarct size and CK-MB, accompanied with decreased PKCβ2 activation and autophagy in control but not in diabetic rats. Pretreatment with CGP53353, a selective inhibitor of PKCβ2, attenuated myocardial I/R-induced infarction and autophagy and restored IPostC-mediated cardioprotection in diabetes. Similarly, CGP53353 could restore hypoxic postconditioning (HPostC) protection against hypoxia reoxygenation- (HR-) induced injury evidenced by decreased LDH release and JC-1 monomeric cells and increased cell viability. These beneficial effects of CGP53353 were reversed by autophagy inducer rapamycin, but could be mimicked by autophagy inhibitor 3-MA. It is concluded that selective inhibition of PKCβ2 could attenuate myocardial I/R injury and restore IPostC-mediated cardioprotection possibly through modulating autophagy in diabetes. Hindawi 2020-04-03 /pmc/articles/PMC7157806/ /pubmed/32337288 http://dx.doi.org/10.1155/2020/2408240 Text en Copyright © 2020 Yafeng Wang et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wang, Yafeng
Zhou, Lu
Su, Wating
Huang, Fengnan
Zhang, Yuan
Xia, Zhong-yuan
Xia, Zhengyuan
Lei, Shaoqing
Selective Inhibition of PKCβ2 Restores Ischemic Postconditioning-Mediated Cardioprotection by Modulating Autophagy in Diabetic Rats
title Selective Inhibition of PKCβ2 Restores Ischemic Postconditioning-Mediated Cardioprotection by Modulating Autophagy in Diabetic Rats
title_full Selective Inhibition of PKCβ2 Restores Ischemic Postconditioning-Mediated Cardioprotection by Modulating Autophagy in Diabetic Rats
title_fullStr Selective Inhibition of PKCβ2 Restores Ischemic Postconditioning-Mediated Cardioprotection by Modulating Autophagy in Diabetic Rats
title_full_unstemmed Selective Inhibition of PKCβ2 Restores Ischemic Postconditioning-Mediated Cardioprotection by Modulating Autophagy in Diabetic Rats
title_short Selective Inhibition of PKCβ2 Restores Ischemic Postconditioning-Mediated Cardioprotection by Modulating Autophagy in Diabetic Rats
title_sort selective inhibition of pkcβ2 restores ischemic postconditioning-mediated cardioprotection by modulating autophagy in diabetic rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157806/
https://www.ncbi.nlm.nih.gov/pubmed/32337288
http://dx.doi.org/10.1155/2020/2408240
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