title: The role of SUMO-1 in cardiac oxidative stress and hypertrophy.
abstract: OBJECTIVE
  Small ubiquitin-like modifier type 1 (SUMO-1) has been shown to play a critical role in the dysfunction of the cardiac isoform of sarcoplasmic reticulum calcium ATPase (SERCA2a) pump in the setting of heart failure. In cardiac hypertrophy, the role of SUMO-1 has not been defined and our study's goals were to examine the effects of modulating SUMO-1 on the hypertrophic response both in vitro and in vivo and to examine whether oxidative stress (during cardiac hypertrophy) is abrogated by SUMO-1 gene transfer.
  
  
  RESULTS
  In mice undergoing transverse aortic constriction (TAC), SUMO-1 levels increased slightly during the compensated stage of hypertrophy and then dropped sharply during the transition to heart failure. In isolated cardiomyocytes, SUMO-1 gene transfer inhibited the hypertrophic response in the presence of phenylephrine. Adeno-associated vector type 9 (AAV9) gene transfer of SUMO-1 prevented the heart from undergoing hypertrophy after TAC and prevented the development of left ventricular dysfunction. Furthermore, SUMO-1 gene transfer blocked the negative effects of H2O2 on SERCA2a activity in cardiac myocytes, while in vivo indices of oxidative stress were decreased by SUMO-1 in cardiac hypertrophy and heart failure.
  
  
  CONCLUSIONS
  The results of this study indicate that post-translational modifications of SERCA2a caused by the toxic environment of the hypertrophied and failing myocardium can be prevented by SUMO-1. Antioxid. Redox Signal. 21, 1986-2001.
authors.affiliation: 1 Department of Cardiology, Cardiovascular Research Center , Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Ahyoung
authors.initials: A
authors.lastname: Lee
authors.forename: Dongtak
authors.initials: D
authors.lastname: Jeong
authors.forename: Shinichi
authors.initials: S
authors.lastname: Mitsuyama
authors.forename: Jae Gyun
authors.initials: JG
authors.lastname: Oh
authors.forename: Lifan
authors.initials: L
authors.lastname: Liang
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Junichi
authors.initials: J
authors.lastname: Sadoshima
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
authors.forename: Changwon
authors.initials: C
authors.lastname: Kho
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D018390:Gene Targeting; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D025842:SUMO-1 Protein / Q000235:genetics* / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*
chemical_list: D025842:SUMO-1 Protein; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium