Ubiquitin-specific protease 7 regulates myocardial ischemia/reperfusion injury by stabilizing Keap1.
Qiong XuMingke LiuJielei GuSisi LingXiaolin LiuZhenyu LuoYangshuo JinRenjie ChaiWenchao OuShiming LiuNingning LiuPublished in: Cell death discovery (2022)
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.
Keyphrases
- ischemia reperfusion injury
- left ventricular
- oxidative stress
- reactive oxygen species
- heart failure
- small molecule
- signaling pathway
- poor prognosis
- cell proliferation
- skeletal muscle
- machine learning
- long non coding rna
- artificial intelligence
- electronic health record
- deep learning
- big data
- high fat diet induced
- binding protein