title: SENP1 protects against myocardial ischaemia/reperfusion injury via a HIF1α-dependent pathway.
abstract: OBJECTIVE
  SUMO-specific protease 1 (SENP1) removes SUMO from proteins and plays important roles in the regulation of multiple cellular signalling pathways. However, little is known about the role of SENP1 in coronary heart disease. In this study, we tested the hypothesis that SENP1 protects against myocardial ischaemia/reperfusion (I/R) injury and investigated the underlying molecular mechanisms involved.
  
  
  RESULTS
  First, we found that SENP1 levels increased after I/R in human and mouse myocardium in vivo and in rat cardiomyocytes in vitro. We then performed coronary artery ligation to induce I/R injury in wild-type (WT) and heterozygous SENP1-knockdown (SENP1(+/-)) mice. Compared with WT mice, SENP1(+/-) mice had normal cardiac function at baseline but lower systolic function after I/R. Post-I/R myocardial infarction sizes were larger in SENP1(+/-) mice. Furthermore, we demonstrated that SENP1 regulates the expression of hypoxia-inducible factor 1 α (HIF1α), a critical protective factor during I/R, in vivo and in vitro. Overexpression of HIF1α reversed the deteriorating effect of SENP1 knockdown on cellular death.
  
  
  CONCLUSIONS
  Our results suggest that SENP1 deficiency exacerbates I/R injury in cardiomyocytes via a HIF1α-dependent pathway.
authors.affiliation: Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Shanghai 200127, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Cardiology, Shanghai 9th People's Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Cardiology, Shanghai 9th People's Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Shanghai 200127, China.
authors.forename: Lihuang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Key Laboratory for Cell Differentiation and Apoptosis of Chinese Ministry of Education, School of Medicine, Shanghai Jiao Tong University, 280 Chongqing South Road, Shanghai 200025, China.
authors.forename: Jinke
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Key Laboratory for Cell Differentiation and Apoptosis of Chinese Ministry of Education, School of Medicine, Shanghai Jiao Tong University, 280 Chongqing South Road, Shanghai 200025, China renjixuesong@gmail.com ccairong@126.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Cai
authors.affiliation: Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Shanghai 200127, China renjixuesong@gmail.com ccairong@126.com.
authors.forename: Song
authors.initials: S
authors.lastname: Xue
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D055550:Protein Stability; D015398:Signal Transduction; D013318:Stroke Volume; D058207:Sumoylation; D014162:Transfection
chemical_list: C497442:HIF1A protein, human; C497443:Hif1a protein, mouse; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases; C000630128:SENP1 protein, rat; C501974:Senp1 protein, mouse
keywords: Apoptosis; Cardiac function; HIF1α; Ischaemia/reperfusion; SENP1