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

Qiong Xu; Mingke Liu; Jielei Gu; Sisi Ling; Xiaolin Liu; Zhenyu Luo; Yangshuo Jin; Renjie Chai; Wenchao Ou; Shiming Liu; Ningning Liu

doi:10.1038/s41420-022-01086-2

Cell Death Discovery (Jun 2022)

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

Qiong Xu,
Mingke Liu,
Jielei Gu,
Sisi Ling,
Xiaolin Liu,
Zhenyu Luo,
Yangshuo Jin,
Renjie Chai,
Wenchao Ou,
Shiming Liu,
Ningning Liu

Affiliations

Qiong Xu: Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, the Second Affiliated Hospital, Guangzhou Medical University
Mingke Liu: Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, the Second Affiliated Hospital, Guangzhou Medical University
Jielei Gu: Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, the Second Affiliated Hospital, Guangzhou Medical University
Sisi Ling: Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, the Second Affiliated Hospital, Guangzhou Medical University
Xiaolin Liu: Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, the Second Affiliated Hospital, Guangzhou Medical University
Zhenyu Luo: Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, the Second Affiliated Hospital, Guangzhou Medical University
Yangshuo Jin: Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, the Second Affiliated Hospital, Guangzhou Medical University
Renjie Chai: Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, the Second Affiliated Hospital, Guangzhou Medical University
Wenchao Ou: Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, the Second Affiliated Hospital, Guangzhou Medical University
Shiming Liu: Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, the Second Affiliated Hospital, Guangzhou Medical University
Ningning Liu: Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, the Second Affiliated Hospital, Guangzhou Medical University

DOI: https://doi.org/10.1038/s41420-022-01086-2
Journal volume & issue: Vol. 8, no. 1
pp. 1 – 10

Abstract

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Abstract 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.

Published in Cell Death Discovery

ISSN: 2058-7716 (Online)
Publisher: Nature Publishing Group
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Science: Biology (General): Cytology
Website: http://www.nature.com/cddiscovery/

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