TY - JOUR
T1 - Ubiquitin-specific protease 7 regulates myocardial ischemia/reperfusion injury by stabilizing Keap1
AU - Xu, Qiong
AU - Liu, Mingke
AU - Gu, Jielei
AU - Ling, Sisi
AU - Liu, Xiaolin
AU - Luo, Zhenyu
AU - Jin, Yangshuo
AU - Chai, Renjie
AU - Ou, Wenchao
AU - Liu, Shiming
AU - Liu, Ningning
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85132299493&partnerID=8YFLogxK
U2 - 10.1038/s41420-022-01086-2
DO - 10.1038/s41420-022-01086-2
M3 - Article
AN - SCOPUS:85132299493
SN - 2058-7716
VL - 8
JO - Cell Death Discovery
JF - Cell Death Discovery
IS - 1
M1 - 291
ER -
