Mechanical stress triggers cardiomyocyte autophagy through angiotensin II type 1 receptor-mediated p38MAP kinase independently of angiotensin II.

Angiotensin II (Ang II) type 1 (AT1) receptor is known to mediate a variety of physiological actions of Ang II including autophagy. However, the role of AT1 receptor in cardiomyocyte autophagy triggered by mechanical stress still remains elusive. The aim of this study was therefore to examine whethe...

Full description

Saved in:
Bibliographic Details
Main Authors: Li Lin, Chuyi Tang, Jianfeng Xu, Yong Ye, Liqing Weng, Wei Wei, Junbo Ge, Xuebo Liu, Yunzeng Zou
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089629&type=printable
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850189795447275520
author Li Lin
Chuyi Tang
Jianfeng Xu
Yong Ye
Liqing Weng
Wei Wei
Junbo Ge
Xuebo Liu
Yunzeng Zou
author_facet Li Lin
Chuyi Tang
Jianfeng Xu
Yong Ye
Liqing Weng
Wei Wei
Junbo Ge
Xuebo Liu
Yunzeng Zou
author_sort Li Lin
collection DOAJ
description Angiotensin II (Ang II) type 1 (AT1) receptor is known to mediate a variety of physiological actions of Ang II including autophagy. However, the role of AT1 receptor in cardiomyocyte autophagy triggered by mechanical stress still remains elusive. The aim of this study was therefore to examine whether and how AT1 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 AT1 receptor blocker, but not PD123319, the AT2 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 AT1 receptor-mediated activation of p38MAP kinase independently of Ang II.
format Article
id doaj-art-0d237468506741e7bfceb3474efd8331
institution OA Journals
issn 1932-6203
language English
publishDate 2014-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-0d237468506741e7bfceb3474efd83312025-08-20T02:15:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8962910.1371/journal.pone.0089629Mechanical stress triggers cardiomyocyte autophagy through angiotensin II type 1 receptor-mediated p38MAP kinase independently of angiotensin II.Li LinChuyi TangJianfeng XuYong YeLiqing WengWei WeiJunbo GeXuebo LiuYunzeng ZouAngiotensin II (Ang II) type 1 (AT1) receptor is known to mediate a variety of physiological actions of Ang II including autophagy. However, the role of AT1 receptor in cardiomyocyte autophagy triggered by mechanical stress still remains elusive. The aim of this study was therefore to examine whether and how AT1 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 AT1 receptor blocker, but not PD123319, the AT2 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 AT1 receptor-mediated activation of p38MAP kinase independently of Ang II.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089629&type=printable
spellingShingle Li Lin
Chuyi Tang
Jianfeng Xu
Yong Ye
Liqing Weng
Wei Wei
Junbo Ge
Xuebo Liu
Yunzeng Zou
Mechanical stress triggers cardiomyocyte autophagy through angiotensin II type 1 receptor-mediated p38MAP kinase independently of angiotensin II.
PLoS ONE
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
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089629&type=printable
work_keys_str_mv AT lilin mechanicalstresstriggerscardiomyocyteautophagythroughangiotensiniitype1receptormediatedp38mapkinaseindependentlyofangiotensinii
AT chuyitang mechanicalstresstriggerscardiomyocyteautophagythroughangiotensiniitype1receptormediatedp38mapkinaseindependentlyofangiotensinii
AT jianfengxu mechanicalstresstriggerscardiomyocyteautophagythroughangiotensiniitype1receptormediatedp38mapkinaseindependentlyofangiotensinii
AT yongye mechanicalstresstriggerscardiomyocyteautophagythroughangiotensiniitype1receptormediatedp38mapkinaseindependentlyofangiotensinii
AT liqingweng mechanicalstresstriggerscardiomyocyteautophagythroughangiotensiniitype1receptormediatedp38mapkinaseindependentlyofangiotensinii
AT weiwei mechanicalstresstriggerscardiomyocyteautophagythroughangiotensiniitype1receptormediatedp38mapkinaseindependentlyofangiotensinii
AT junboge mechanicalstresstriggerscardiomyocyteautophagythroughangiotensiniitype1receptormediatedp38mapkinaseindependentlyofangiotensinii
AT xueboliu mechanicalstresstriggerscardiomyocyteautophagythroughangiotensiniitype1receptormediatedp38mapkinaseindependentlyofangiotensinii
AT yunzengzou mechanicalstresstriggerscardiomyocyteautophagythroughangiotensiniitype1receptormediatedp38mapkinaseindependentlyofangiotensinii