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Klotho overexpression suppresses apoptosis by regulating the Hsp70/Akt/Bad pathway in H9c2(2-1) cells

Early reperfusion is the most effective and important treatment for acute myocardial infarction. However, reperfusion therapy often leads to a certain degree of myocardial damage. The aim of the present study was to identify the role of klotho, and the molecular mechanism underlying its effects, in...

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Autores principales: Hu, Jinpeng, Su, Bin, Li, Xuewen, Li, Yuming, Zhao, Jihong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005687/
https://www.ncbi.nlm.nih.gov/pubmed/33790995
http://dx.doi.org/10.3892/etm.2021.9917
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author Hu, Jinpeng
Su, Bin
Li, Xuewen
Li, Yuming
Zhao, Jihong
author_facet Hu, Jinpeng
Su, Bin
Li, Xuewen
Li, Yuming
Zhao, Jihong
author_sort Hu, Jinpeng
collection PubMed
description Early reperfusion is the most effective and important treatment for acute myocardial infarction. However, reperfusion therapy often leads to a certain degree of myocardial damage. The aim of the present study was to identify the role of klotho, and the molecular mechanism underlying its effects, in myocardial damage using a model of myocardial hypoxia injury. Hypoxia/reoxygenation (H/R) was used to mimic ischemia/reperfusion (I/R) injury in vitro. The expression and distribution of klotho in H9c2(2-1) cells was observed by fluorogenic scanning, and the apoptotic rate was determined by Annexin V-FITC/propidium iodide dual staining. Cell viability was determined by MTT assay, and caspase-3, cleaved caspase-3, Bcl-2, Bax, heat shock protein (Hsp) 70 and Akt levels were assessed by western blotting. A lactate dehydrogenase test was performed to determine the degree of H9c2(2-1) cell damage. The results revealed that klotho was primarily located in the cytoplasm of H9c2(2-1) cells. Klotho overexpression markedly suppressed H/R-induced H9c2(2-1) cell apoptosis. Furthermore, cell viability increased, and injury decreased in response to klotho. Klotho also suppressed the activation of caspase-3, upregulated Bcl2 and decreased Bax levels following H/R injury, as well as alleviating H/R injury by upregulating the expression of Hsp70 and increasing the levels of phosphorylated (p-)Akt and Bad. In conclusion, these results indicate that klotho suppressed H/R-induced H9c2(2-1) cell apoptosis by regulating the levels of Hsp70, p-Akt and p-Bad, which suggest that klotho could be a novel agent for the treatment of coronary disease.
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spelling pubmed-80056872021-03-30 Klotho overexpression suppresses apoptosis by regulating the Hsp70/Akt/Bad pathway in H9c2(2-1) cells Hu, Jinpeng Su, Bin Li, Xuewen Li, Yuming Zhao, Jihong Exp Ther Med Articles Early reperfusion is the most effective and important treatment for acute myocardial infarction. However, reperfusion therapy often leads to a certain degree of myocardial damage. The aim of the present study was to identify the role of klotho, and the molecular mechanism underlying its effects, in myocardial damage using a model of myocardial hypoxia injury. Hypoxia/reoxygenation (H/R) was used to mimic ischemia/reperfusion (I/R) injury in vitro. The expression and distribution of klotho in H9c2(2-1) cells was observed by fluorogenic scanning, and the apoptotic rate was determined by Annexin V-FITC/propidium iodide dual staining. Cell viability was determined by MTT assay, and caspase-3, cleaved caspase-3, Bcl-2, Bax, heat shock protein (Hsp) 70 and Akt levels were assessed by western blotting. A lactate dehydrogenase test was performed to determine the degree of H9c2(2-1) cell damage. The results revealed that klotho was primarily located in the cytoplasm of H9c2(2-1) cells. Klotho overexpression markedly suppressed H/R-induced H9c2(2-1) cell apoptosis. Furthermore, cell viability increased, and injury decreased in response to klotho. Klotho also suppressed the activation of caspase-3, upregulated Bcl2 and decreased Bax levels following H/R injury, as well as alleviating H/R injury by upregulating the expression of Hsp70 and increasing the levels of phosphorylated (p-)Akt and Bad. In conclusion, these results indicate that klotho suppressed H/R-induced H9c2(2-1) cell apoptosis by regulating the levels of Hsp70, p-Akt and p-Bad, which suggest that klotho could be a novel agent for the treatment of coronary disease. D.A. Spandidos 2021-05 2021-03-16 /pmc/articles/PMC8005687/ /pubmed/33790995 http://dx.doi.org/10.3892/etm.2021.9917 Text en Copyright: © Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Hu, Jinpeng
Su, Bin
Li, Xuewen
Li, Yuming
Zhao, Jihong
Klotho overexpression suppresses apoptosis by regulating the Hsp70/Akt/Bad pathway in H9c2(2-1) cells
title Klotho overexpression suppresses apoptosis by regulating the Hsp70/Akt/Bad pathway in H9c2(2-1) cells
title_full Klotho overexpression suppresses apoptosis by regulating the Hsp70/Akt/Bad pathway in H9c2(2-1) cells
title_fullStr Klotho overexpression suppresses apoptosis by regulating the Hsp70/Akt/Bad pathway in H9c2(2-1) cells
title_full_unstemmed Klotho overexpression suppresses apoptosis by regulating the Hsp70/Akt/Bad pathway in H9c2(2-1) cells
title_short Klotho overexpression suppresses apoptosis by regulating the Hsp70/Akt/Bad pathway in H9c2(2-1) cells
title_sort klotho overexpression suppresses apoptosis by regulating the hsp70/akt/bad pathway in h9c2(2-1) cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005687/
https://www.ncbi.nlm.nih.gov/pubmed/33790995
http://dx.doi.org/10.3892/etm.2021.9917
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