Cargando…

SIRT1 Protects the Heart from ER Stress-Induced Injury by Promoting eEF2K/eEF2-Dependent Autophagy

Many recent studies have demonstrated the involvement of endoplasmic reticulum (ER) stress in the development of cardiac diseases and have suggested that modulation of ER stress response could be cardioprotective. Previously, we demonstrated that the deacetylase Sirtuin 1 (SIRT1) attenuates ER stres...

Descripción completa

Detalles Bibliográficos
Autores principales: Pires Da Silva, Julie, Monceaux, Kevin, Guilbert, Arnaud, Gressette, Mélanie, Piquereau, Jérôme, Novotova, Marta, Ventura-Clapier, Renée, Garnier, Anne, Lemaire, Christophe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072417/
https://www.ncbi.nlm.nih.gov/pubmed/32059483
http://dx.doi.org/10.3390/cells9020426
_version_ 1783506401554857984
author Pires Da Silva, Julie
Monceaux, Kevin
Guilbert, Arnaud
Gressette, Mélanie
Piquereau, Jérôme
Novotova, Marta
Ventura-Clapier, Renée
Garnier, Anne
Lemaire, Christophe
author_facet Pires Da Silva, Julie
Monceaux, Kevin
Guilbert, Arnaud
Gressette, Mélanie
Piquereau, Jérôme
Novotova, Marta
Ventura-Clapier, Renée
Garnier, Anne
Lemaire, Christophe
author_sort Pires Da Silva, Julie
collection PubMed
description Many recent studies have demonstrated the involvement of endoplasmic reticulum (ER) stress in the development of cardiac diseases and have suggested that modulation of ER stress response could be cardioprotective. Previously, we demonstrated that the deacetylase Sirtuin 1 (SIRT1) attenuates ER stress response and promotes cardiomyocyte survival. Here, we investigated whether and how autophagy plays a role in SIRT1-afforded cardioprotection against ER stress. The results revealed that protective autophagy was initiated before cell death in response to tunicamycin (TN)-induced ER stress in cardiac cells. SIRT1 inhibition decreased ER stress-induced autophagy, whereas its activation enhanced autophagy. In response to TN- or isoproterenol-induced ER stress, mice deficient for SIRT1 exhibited suppressed autophagy along with exacerbated cardiac dysfunction. At the molecular level, we found that in response to ER stress (i) the extinction of eEF2 or its kinase eEF2K not only reduced autophagy but further activated cell death, (ii) inhibition of SIRT1 inhibited the phosphorylation of eEF2, (iii) eIF2α co-immunoprecipitated with eEF2K, and (iv) knockdown of eIF2α reduced the phosphorylation of eEF2. Our results indicate that in response to ER stress, SIRT1 activation promotes cardiomyocyte survival by enhancing autophagy at least through activation of the eEF2K/eEF2 pathway.
format Online
Article
Text
id pubmed-7072417
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-70724172020-03-19 SIRT1 Protects the Heart from ER Stress-Induced Injury by Promoting eEF2K/eEF2-Dependent Autophagy Pires Da Silva, Julie Monceaux, Kevin Guilbert, Arnaud Gressette, Mélanie Piquereau, Jérôme Novotova, Marta Ventura-Clapier, Renée Garnier, Anne Lemaire, Christophe Cells Article Many recent studies have demonstrated the involvement of endoplasmic reticulum (ER) stress in the development of cardiac diseases and have suggested that modulation of ER stress response could be cardioprotective. Previously, we demonstrated that the deacetylase Sirtuin 1 (SIRT1) attenuates ER stress response and promotes cardiomyocyte survival. Here, we investigated whether and how autophagy plays a role in SIRT1-afforded cardioprotection against ER stress. The results revealed that protective autophagy was initiated before cell death in response to tunicamycin (TN)-induced ER stress in cardiac cells. SIRT1 inhibition decreased ER stress-induced autophagy, whereas its activation enhanced autophagy. In response to TN- or isoproterenol-induced ER stress, mice deficient for SIRT1 exhibited suppressed autophagy along with exacerbated cardiac dysfunction. At the molecular level, we found that in response to ER stress (i) the extinction of eEF2 or its kinase eEF2K not only reduced autophagy but further activated cell death, (ii) inhibition of SIRT1 inhibited the phosphorylation of eEF2, (iii) eIF2α co-immunoprecipitated with eEF2K, and (iv) knockdown of eIF2α reduced the phosphorylation of eEF2. Our results indicate that in response to ER stress, SIRT1 activation promotes cardiomyocyte survival by enhancing autophagy at least through activation of the eEF2K/eEF2 pathway. MDPI 2020-02-12 /pmc/articles/PMC7072417/ /pubmed/32059483 http://dx.doi.org/10.3390/cells9020426 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pires Da Silva, Julie
Monceaux, Kevin
Guilbert, Arnaud
Gressette, Mélanie
Piquereau, Jérôme
Novotova, Marta
Ventura-Clapier, Renée
Garnier, Anne
Lemaire, Christophe
SIRT1 Protects the Heart from ER Stress-Induced Injury by Promoting eEF2K/eEF2-Dependent Autophagy
title SIRT1 Protects the Heart from ER Stress-Induced Injury by Promoting eEF2K/eEF2-Dependent Autophagy
title_full SIRT1 Protects the Heart from ER Stress-Induced Injury by Promoting eEF2K/eEF2-Dependent Autophagy
title_fullStr SIRT1 Protects the Heart from ER Stress-Induced Injury by Promoting eEF2K/eEF2-Dependent Autophagy
title_full_unstemmed SIRT1 Protects the Heart from ER Stress-Induced Injury by Promoting eEF2K/eEF2-Dependent Autophagy
title_short SIRT1 Protects the Heart from ER Stress-Induced Injury by Promoting eEF2K/eEF2-Dependent Autophagy
title_sort sirt1 protects the heart from er stress-induced injury by promoting eef2k/eef2-dependent autophagy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072417/
https://www.ncbi.nlm.nih.gov/pubmed/32059483
http://dx.doi.org/10.3390/cells9020426
work_keys_str_mv AT piresdasilvajulie sirt1protectstheheartfromerstressinducedinjurybypromotingeef2keef2dependentautophagy
AT monceauxkevin sirt1protectstheheartfromerstressinducedinjurybypromotingeef2keef2dependentautophagy
AT guilbertarnaud sirt1protectstheheartfromerstressinducedinjurybypromotingeef2keef2dependentautophagy
AT gressettemelanie sirt1protectstheheartfromerstressinducedinjurybypromotingeef2keef2dependentautophagy
AT piquereaujerome sirt1protectstheheartfromerstressinducedinjurybypromotingeef2keef2dependentautophagy
AT novotovamarta sirt1protectstheheartfromerstressinducedinjurybypromotingeef2keef2dependentautophagy
AT venturaclapierrenee sirt1protectstheheartfromerstressinducedinjurybypromotingeef2keef2dependentautophagy
AT garnieranne sirt1protectstheheartfromerstressinducedinjurybypromotingeef2keef2dependentautophagy
AT lemairechristophe sirt1protectstheheartfromerstressinducedinjurybypromotingeef2keef2dependentautophagy