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Tsg101 positively regulates P62-Keap1-Nrf2 pathway to protect hearts against oxidative damage

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WOS体系：
Pubmed体系：

收录情况： ◇ SCIE

作者：
Deng, Shan[1,2,3] * ; Essandoh, Kobina[2] * ; Wang, Xiaohong[2] ; Li, Yutian[2] ; Huang, Wei[4] ; Chen, Jing[5] ; Peng, Jiangtong[1,3] ; Jiang, Ding-Sheng[6] ; Mu, Xingjiang[2] ; Wang, Chenran[7] ; Peng, Tianqing[8] ; Guan, Jun-Lin[7] ; Wang, Yigang[4] ; Jegga, Anil[5] ; Huang, Kai[1,3] ; Fan, Guo-Chang[2] ;
单位： [1]Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China [2]Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA [3]Clinical Center for Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China [4]Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA [5]Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA [6]Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China [7]Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA [8]Critical Illness Research, Lawson Health Research Institute, Ontario, Canada
出处：
DOI： 10.1016/j.redox.2020.101453
ISSN：

关键词： Oxidative stress Myocardial ischemia-reperfusion Nrf2 p62 aggregation Cardiac autophagy Tsg101

摘要：
Currently, most antioxidants do not show any favorable clinical outcomes in reducing myocardial ischemia-reperfusion (I/R) injury, suggesting an urgent need for exploring a new regulator of redox homeostasis in I/R hearts. Here, using heart-specific transgenic (TG) and knockdown (KD) mouse models, tumor susceptibility gene 101 (Tsg101) is defined as a novel cardiac-protector against I/R-triggered oxidative stress. RNA sequencing and bioinformatics data surprisingly reveal that most upregulated genes in Tsg101-TG hearts are transcribed by Nrf2. Accordingly, pharmacological inhibition of Nrf2 offsets Tsg101-elicited cardio-protection. Mechanistically, Tsg101 interacts with SQSTM1/p62 through its PRR domain, and promotes p62 aggregation, leading to recruitment of Keap1 for degradation by autophagosomes and release of Nrf2 to the nucleus. Furthermore, knockout of p62 abrogates Tsg101-induced cardio-protective effects during I/R. Hence, our findings uncover a previously unrecognized role of Tsg101 in the regulation of p62/Keap1/Nrf2 signaling cascades and provide a new strategy for the treatment of ischemic heart disease.

基金：
National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 GM-126061, GM-132149]; American Heart Association (AHA) Established Investigator AwardAmerican Heart Association [17EIA33400063]; AHA Pre-doctoral FellowshipAmerican Heart Association [18PRE34030123]

基金编号： R01 GM-126061 GM-132149 17EIA33400063 18PRE34030123

语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类 | 1 区 生物
小类 | 2 区 生化与分子生物学
最新[2025]版：
大类 | 1 区 生物学
小类 | 1 区 生化与分子生物学
JCR分区：
出版当年[2018]版：
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版：
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2018版] 出版当年五年平均 出版前一年[2017版] 出版后一年[2019版]

第一作者：
第一作者单位： [1]Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China [2]Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA [3]Clinical Center for Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
共同第一作者：
通讯作者：
通讯机构： [2]Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA
推荐引用方式(GB/T 7714)：
Deng Shan,Essandoh Kobina,Wang Xiaohong,et al.Tsg101 positively regulates P62-Keap1-Nrf2 pathway to protect hearts against oxidative damage[J].REDOX BIOLOGY.2020,32:doi:10.1016/j.redox.2020.101453.
APA：
Deng, Shan,Essandoh, Kobina,Wang, Xiaohong,Li, Yutian,Huang, Wei...&Fan, Guo-Chang.(2020).Tsg101 positively regulates P62-Keap1-Nrf2 pathway to protect hearts against oxidative damage.REDOX BIOLOGY,32,
MLA：
Deng, Shan,et al."Tsg101 positively regulates P62-Keap1-Nrf2 pathway to protect hearts against oxidative damage".REDOX BIOLOGY 32.(2020)

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