Mechanical Stress Triggers Cardiomyocyte Autophagy through Angiotensin II Type 1 Receptor-Mediated p38MAP Kinase Independently of Angiotensin II
Angiotensin II (Ang II) type 1 (AT(1)) receptor is known to mediate a variety of physiological actions of Ang II including autophagy. However, the role of AT(1) receptor in cardiomyocyte autophagy triggered by mechanical stress still remains elusive. The aim of this study was therefore to examine wh...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931796/ https://www.ncbi.nlm.nih.gov/pubmed/24586922 http://dx.doi.org/10.1371/journal.pone.0089629 |
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author | Lin, Li Tang, Chuyi Xu, Jianfeng Ye, Yong Weng, Liqing Wei, Wei Ge, Junbo Liu, Xuebo Zou, Yunzeng |
author_facet | Lin, Li Tang, Chuyi Xu, Jianfeng Ye, Yong Weng, Liqing Wei, Wei Ge, Junbo Liu, Xuebo Zou, Yunzeng |
author_sort | Lin, Li |
collection | PubMed |
description | Angiotensin II (Ang II) type 1 (AT(1)) receptor is known to mediate a variety of physiological actions of Ang II including autophagy. However, the role of AT(1) receptor in cardiomyocyte autophagy triggered by mechanical stress still remains elusive. The aim of this study was therefore to examine whether and how AT(1) receptor participates in cardiomyocyte autophagy induced by mechanical stresses. A 48-hour mechanical stretch and a 4-week transverse aorta constriction (TAC) were imposed to cultured cardiomyocytes of neonatal rats and adult male C57B/L6 mice, respectively, to induce cardiomyocyte hypertrophy prior to the assessment of cardiomyocyte autophagy using LC3b-II. Losartan, an AT(1) receptor blocker, but not PD123319, the AT(2) inhibitor, was found to significantly reduce mechanical stretch-induced LC3b-II upregulation. Moreover, inhibition of p38MAP kinase attenuated not only mechanical stretch-induced cardiomyocyte hypertrophy but also autophagy. To the contrary, inhibition of ERK and JNK suppressed cardiac hypertrophy but not autophagy. Intriguingly, mechanical stretch-induced autophagy was significantly inhibited by Losartan in the absence of Ang II. Taken together, our results indicate that mechanical stress triggers cardiomyocyte autophagy through AT(1) receptor-mediated activation of p38MAP kinase independently of Ang II. |
format | Online Article Text |
id | pubmed-3931796 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39317962014-02-25 Mechanical Stress Triggers Cardiomyocyte Autophagy through Angiotensin II Type 1 Receptor-Mediated p38MAP Kinase Independently of Angiotensin II Lin, Li Tang, Chuyi Xu, Jianfeng Ye, Yong Weng, Liqing Wei, Wei Ge, Junbo Liu, Xuebo Zou, Yunzeng PLoS One Research Article Angiotensin II (Ang II) type 1 (AT(1)) receptor is known to mediate a variety of physiological actions of Ang II including autophagy. However, the role of AT(1) receptor in cardiomyocyte autophagy triggered by mechanical stress still remains elusive. The aim of this study was therefore to examine whether and how AT(1) receptor participates in cardiomyocyte autophagy induced by mechanical stresses. A 48-hour mechanical stretch and a 4-week transverse aorta constriction (TAC) were imposed to cultured cardiomyocytes of neonatal rats and adult male C57B/L6 mice, respectively, to induce cardiomyocyte hypertrophy prior to the assessment of cardiomyocyte autophagy using LC3b-II. Losartan, an AT(1) receptor blocker, but not PD123319, the AT(2) inhibitor, was found to significantly reduce mechanical stretch-induced LC3b-II upregulation. Moreover, inhibition of p38MAP kinase attenuated not only mechanical stretch-induced cardiomyocyte hypertrophy but also autophagy. To the contrary, inhibition of ERK and JNK suppressed cardiac hypertrophy but not autophagy. Intriguingly, mechanical stretch-induced autophagy was significantly inhibited by Losartan in the absence of Ang II. Taken together, our results indicate that mechanical stress triggers cardiomyocyte autophagy through AT(1) receptor-mediated activation of p38MAP kinase independently of Ang II. Public Library of Science 2014-02-21 /pmc/articles/PMC3931796/ /pubmed/24586922 http://dx.doi.org/10.1371/journal.pone.0089629 Text en © 2014 Lin et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lin, Li Tang, Chuyi Xu, Jianfeng Ye, Yong Weng, Liqing Wei, Wei Ge, Junbo Liu, Xuebo Zou, Yunzeng Mechanical Stress Triggers Cardiomyocyte Autophagy through Angiotensin II Type 1 Receptor-Mediated p38MAP Kinase Independently of Angiotensin II |
title | Mechanical Stress Triggers Cardiomyocyte Autophagy through Angiotensin II Type 1 Receptor-Mediated p38MAP Kinase Independently of Angiotensin II |
title_full | Mechanical Stress Triggers Cardiomyocyte Autophagy through Angiotensin II Type 1 Receptor-Mediated p38MAP Kinase Independently of Angiotensin II |
title_fullStr | Mechanical Stress Triggers Cardiomyocyte Autophagy through Angiotensin II Type 1 Receptor-Mediated p38MAP Kinase Independently of Angiotensin II |
title_full_unstemmed | Mechanical Stress Triggers Cardiomyocyte Autophagy through Angiotensin II Type 1 Receptor-Mediated p38MAP Kinase Independently of Angiotensin II |
title_short | Mechanical Stress Triggers Cardiomyocyte Autophagy through Angiotensin II Type 1 Receptor-Mediated p38MAP Kinase Independently of Angiotensin II |
title_sort | mechanical stress triggers cardiomyocyte autophagy through angiotensin ii type 1 receptor-mediated p38map kinase independently of angiotensin ii |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931796/ https://www.ncbi.nlm.nih.gov/pubmed/24586922 http://dx.doi.org/10.1371/journal.pone.0089629 |
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