Rapamycin inhibits cardiac hypertrophy by promoting autophagy via the MEK/ERK/Beclin-1 pathway
Rapamycin, also known as sirolimus, is an antifungal agent and immunosuppressant drug used to prevent organ rejection in transplantation. However, little is known about the role of rapamycin in cardiac hypertrophy and the signaling pathways involved. Here, the effect of rapamycin was examined using...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2016-03-01
|
Series: | Frontiers in Physiology |
Subjects: | |
Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00104/full |
id |
doaj-939bac23929643f8a478e416e00aee1d |
---|---|
record_format |
Article |
spelling |
doaj-939bac23929643f8a478e416e00aee1d2020-11-25T01:07:42ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2016-03-01710.3389/fphys.2016.00104184300Rapamycin inhibits cardiac hypertrophy by promoting autophagy via the MEK/ERK/Beclin-1 pathwayChangqian eWang0Gu eJun1Gu eJun2Wei eHu3Zhi-ping eSong4Yue-guang eChen5Da-dong eZhang6Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of ChinaDepartment of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of ChinaShanghai Minhang Hospital, Fudan University, Shanghai, People's Republic of ChinaShanghai Minhang Hospital, Fudan University, Shanghai, People's Republic of ChinaShanghai Minhang Hospital, Fudan University, Shanghai, People's Republic of ChinaShanghai Minhang Hospital, Fudan University, Shanghai, People's Republic of ChinaShanghai Minhang Hospital, Fudan University, Shanghai, People's Republic of ChinaRapamycin, also known as sirolimus, is an antifungal agent and immunosuppressant drug used to prevent organ rejection in transplantation. However, little is known about the role of rapamycin in cardiac hypertrophy and the signaling pathways involved. Here, the effect of rapamycin was examined using phenylephrine (PE) induced cardiomyocyte hypertrophy in vitro and in a rat model of aortic banding (AB)-induced hypertrophy in vivo. Inhibition of MEK/ERK signaling reversed the effect of rapamycin on the upregulation of LC3-II, Beclin-1 and Noxa, and the downregulation of Mcl-1 and p62. Silencing of Noxa or Beclin-1 suppressed rapamycin-induced autophagy, and co-immunoprecipitation experiments showed that Noxa abolishes the inhibitory effect of Mcl-1 on Beclin-1, promoting autophagy. In vivo experiments showed that rapamycin decreased AB-induced cardiac hypertrophy in a MEK/ERK dependent manner. Taken together, our results indicate that rapamycin attenuates cardiac hypertrophy by promoting autophagy through a mechanism involving the modulation of Noxa and Beclin-1 expression by the MEK/ERK signaling pathway.http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00104/fullAutophagycardiac hypertrophyrapamycinAortic bandingMEK/ERK signaling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Changqian eWang Gu eJun Gu eJun Wei eHu Zhi-ping eSong Yue-guang eChen Da-dong eZhang |
spellingShingle |
Changqian eWang Gu eJun Gu eJun Wei eHu Zhi-ping eSong Yue-guang eChen Da-dong eZhang Rapamycin inhibits cardiac hypertrophy by promoting autophagy via the MEK/ERK/Beclin-1 pathway Frontiers in Physiology Autophagy cardiac hypertrophy rapamycin Aortic banding MEK/ERK signaling |
author_facet |
Changqian eWang Gu eJun Gu eJun Wei eHu Zhi-ping eSong Yue-guang eChen Da-dong eZhang |
author_sort |
Changqian eWang |
title |
Rapamycin inhibits cardiac hypertrophy by promoting autophagy via the MEK/ERK/Beclin-1 pathway |
title_short |
Rapamycin inhibits cardiac hypertrophy by promoting autophagy via the MEK/ERK/Beclin-1 pathway |
title_full |
Rapamycin inhibits cardiac hypertrophy by promoting autophagy via the MEK/ERK/Beclin-1 pathway |
title_fullStr |
Rapamycin inhibits cardiac hypertrophy by promoting autophagy via the MEK/ERK/Beclin-1 pathway |
title_full_unstemmed |
Rapamycin inhibits cardiac hypertrophy by promoting autophagy via the MEK/ERK/Beclin-1 pathway |
title_sort |
rapamycin inhibits cardiac hypertrophy by promoting autophagy via the mek/erk/beclin-1 pathway |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2016-03-01 |
description |
Rapamycin, also known as sirolimus, is an antifungal agent and immunosuppressant drug used to prevent organ rejection in transplantation. However, little is known about the role of rapamycin in cardiac hypertrophy and the signaling pathways involved. Here, the effect of rapamycin was examined using phenylephrine (PE) induced cardiomyocyte hypertrophy in vitro and in a rat model of aortic banding (AB)-induced hypertrophy in vivo. Inhibition of MEK/ERK signaling reversed the effect of rapamycin on the upregulation of LC3-II, Beclin-1 and Noxa, and the downregulation of Mcl-1 and p62. Silencing of Noxa or Beclin-1 suppressed rapamycin-induced autophagy, and co-immunoprecipitation experiments showed that Noxa abolishes the inhibitory effect of Mcl-1 on Beclin-1, promoting autophagy. In vivo experiments showed that rapamycin decreased AB-induced cardiac hypertrophy in a MEK/ERK dependent manner. Taken together, our results indicate that rapamycin attenuates cardiac hypertrophy by promoting autophagy through a mechanism involving the modulation of Noxa and Beclin-1 expression by the MEK/ERK signaling pathway. |
topic |
Autophagy cardiac hypertrophy rapamycin Aortic banding MEK/ERK signaling |
url |
http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00104/full |
work_keys_str_mv |
AT changqianewang rapamycininhibitscardiachypertrophybypromotingautophagyviathemekerkbeclin1pathway AT guejun rapamycininhibitscardiachypertrophybypromotingautophagyviathemekerkbeclin1pathway AT guejun rapamycininhibitscardiachypertrophybypromotingautophagyviathemekerkbeclin1pathway AT weiehu rapamycininhibitscardiachypertrophybypromotingautophagyviathemekerkbeclin1pathway AT zhipingesong rapamycininhibitscardiachypertrophybypromotingautophagyviathemekerkbeclin1pathway AT yueguangechen rapamycininhibitscardiachypertrophybypromotingautophagyviathemekerkbeclin1pathway AT dadongezhang rapamycininhibitscardiachypertrophybypromotingautophagyviathemekerkbeclin1pathway |
_version_ |
1725185773099024384 |