Ubiquitin-specific protease 7 regulates myocardial ischemia/reperfusion injury by stabilizing Keap1

Myocardial ischemia/reperfusion (I/R) injury is a complex pathological process that is still not fully understood. The oxidative stress response has a critical role in the occurrence and progression of myocardial ischemia/reperfusion injury. This study investigated the specific mechanism of ubiquiti...

Descripción completa

Detalles Bibliográficos
Autores principales: Xu, Qiong, Liu, Mingke, Gu, Jielei, Ling, Sisi, Liu, Xiaolin, Luo, Zhenyu, Jin, Yangshuo, Chai, Renjie, Ou, Wenchao, Liu, Shiming, Liu, Ningning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203583/
https://www.ncbi.nlm.nih.gov/pubmed/35710902
http://dx.doi.org/10.1038/s41420-022-01086-2
_version_ 1784728738453258240
author Xu, Qiong
Liu, Mingke
Gu, Jielei
Ling, Sisi
Liu, Xiaolin
Luo, Zhenyu
Jin, Yangshuo
Chai, Renjie
Ou, Wenchao
Liu, Shiming
Liu, Ningning
author_facet Xu, Qiong
Liu, Mingke
Gu, Jielei
Ling, Sisi
Liu, Xiaolin
Luo, Zhenyu
Jin, Yangshuo
Chai, Renjie
Ou, Wenchao
Liu, Shiming
Liu, Ningning
author_sort Xu, Qiong
collection PubMed
description Myocardial ischemia/reperfusion (I/R) injury is a complex pathological process that is still not fully understood. The oxidative stress response has a critical role in the occurrence and progression of myocardial ischemia/reperfusion injury. This study investigated the specific mechanism of ubiquitin-specific protease 7 (USP7) regulation of myocardial ischemia/reperfusion injury from the perspective of proteasome degradation and its relation with the Keap1 pathway, a vital regulator of cytoprotective responses to endogenous and exogenous stress induced by reactive oxygen species (ROS) and electrophiles. Our data indicated that USP7 expression is increased during myocardial ischemia/reperfusion injury in mice, while its inhibiting suppressed the generation of oxygen free radicals and myocardial cell apoptosis, reduced myocardial tissue damage, and improved heart function. Mechanistically, USP7 stabilizes Keap1 by regulating its ubiquitination. Taken together, these findings demonstrate the potential therapeutic effect of USP7 on myocardial ischemia/reperfusion injury.
format Online
Article
Text
id pubmed-9203583
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-92035832022-06-18 Ubiquitin-specific protease 7 regulates myocardial ischemia/reperfusion injury by stabilizing Keap1 Xu, Qiong Liu, Mingke Gu, Jielei Ling, Sisi Liu, Xiaolin Luo, Zhenyu Jin, Yangshuo Chai, Renjie Ou, Wenchao Liu, Shiming Liu, Ningning Cell Death Discov Article Myocardial ischemia/reperfusion (I/R) injury is a complex pathological process that is still not fully understood. The oxidative stress response has a critical role in the occurrence and progression of myocardial ischemia/reperfusion injury. This study investigated the specific mechanism of ubiquitin-specific protease 7 (USP7) regulation of myocardial ischemia/reperfusion injury from the perspective of proteasome degradation and its relation with the Keap1 pathway, a vital regulator of cytoprotective responses to endogenous and exogenous stress induced by reactive oxygen species (ROS) and electrophiles. Our data indicated that USP7 expression is increased during myocardial ischemia/reperfusion injury in mice, while its inhibiting suppressed the generation of oxygen free radicals and myocardial cell apoptosis, reduced myocardial tissue damage, and improved heart function. Mechanistically, USP7 stabilizes Keap1 by regulating its ubiquitination. Taken together, these findings demonstrate the potential therapeutic effect of USP7 on myocardial ischemia/reperfusion injury. Nature Publishing Group UK 2022-06-16 /pmc/articles/PMC9203583/ /pubmed/35710902 http://dx.doi.org/10.1038/s41420-022-01086-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Xu, Qiong
Liu, Mingke
Gu, Jielei
Ling, Sisi
Liu, Xiaolin
Luo, Zhenyu
Jin, Yangshuo
Chai, Renjie
Ou, Wenchao
Liu, Shiming
Liu, Ningning
Ubiquitin-specific protease 7 regulates myocardial ischemia/reperfusion injury by stabilizing Keap1
title Ubiquitin-specific protease 7 regulates myocardial ischemia/reperfusion injury by stabilizing Keap1
title_full Ubiquitin-specific protease 7 regulates myocardial ischemia/reperfusion injury by stabilizing Keap1
title_fullStr Ubiquitin-specific protease 7 regulates myocardial ischemia/reperfusion injury by stabilizing Keap1
title_full_unstemmed Ubiquitin-specific protease 7 regulates myocardial ischemia/reperfusion injury by stabilizing Keap1
title_short Ubiquitin-specific protease 7 regulates myocardial ischemia/reperfusion injury by stabilizing Keap1
title_sort ubiquitin-specific protease 7 regulates myocardial ischemia/reperfusion injury by stabilizing keap1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203583/
https://www.ncbi.nlm.nih.gov/pubmed/35710902
http://dx.doi.org/10.1038/s41420-022-01086-2
work_keys_str_mv AT xuqiong ubiquitinspecificprotease7regulatesmyocardialischemiareperfusioninjurybystabilizingkeap1
AT liumingke ubiquitinspecificprotease7regulatesmyocardialischemiareperfusioninjurybystabilizingkeap1
AT gujielei ubiquitinspecificprotease7regulatesmyocardialischemiareperfusioninjurybystabilizingkeap1
AT lingsisi ubiquitinspecificprotease7regulatesmyocardialischemiareperfusioninjurybystabilizingkeap1
AT liuxiaolin ubiquitinspecificprotease7regulatesmyocardialischemiareperfusioninjurybystabilizingkeap1
AT luozhenyu ubiquitinspecificprotease7regulatesmyocardialischemiareperfusioninjurybystabilizingkeap1
AT jinyangshuo ubiquitinspecificprotease7regulatesmyocardialischemiareperfusioninjurybystabilizingkeap1
AT chairenjie ubiquitinspecificprotease7regulatesmyocardialischemiareperfusioninjurybystabilizingkeap1
AT ouwenchao ubiquitinspecificprotease7regulatesmyocardialischemiareperfusioninjurybystabilizingkeap1
AT liushiming ubiquitinspecificprotease7regulatesmyocardialischemiareperfusioninjurybystabilizingkeap1
AT liuningning ubiquitinspecificprotease7regulatesmyocardialischemiareperfusioninjurybystabilizingkeap1

Ejemplares similares