title: The expression of Ubc9 and the intensity of SERCA2a-SUMOylation were reduced in diet-induced obese rats and partially restored by trimetazidine.
abstract: BACKGROUND
  Reduced expression of sarcoplasmic reticulum calcium-transporting ATPase isoform 2a (SERCA2a) has been shown to play a significant role in the cardiac dysfunction of obese animal models. It was reported recently that SUMOylation enhances the stability and activity of SERCA2a. We hypothesized that SERCA2a-SUMOylation might be involved in obesity-mediated reduction of SERCA2a.
  
  
  RESULTS
  Trimetazidine (TMZ), the drug that inhibits fatty acid oxidation, was used in diet-induced obese (DIO) rats and palmitic acid (PA)-treated cardiomyocytes. The intensity of SERCA2a-SUMOylation and proteins involved in SERCA2a-SUMOylation were investigated in vivo and in vitro. DIO rats presented cardiac dysfunction, which was alleviated by TMZ treatment. Reductions of SERCA2a protein and the intensity of SERCA2a-SUMOylation were observed in DIO rats and PA-treated cardiomyocytes. These reductions were partially restored by TMZ. However, TMZ itself did not alter the intensity of SERCA2a-SUMOylation in control cardiomyocytes. The variations of protein and messenger RNA levels of Ubiquitin carrier protein 9 are in accordance with the intensity of SERCA2a-SUMOylation. Whereas the other proteins involved in SERCA2a-SUMOylation were not changed by DIO and PA.
  
  
  CONCLUSIONS
  TMZ alleviates the DIO- and PA-induced reductions of SERCA2a-SUMOylation. Ubiquitin carrier protein 9 is involved in the reductions.
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yao
authors.forename: Xing-Hui
authors.initials: XH
authors.lastname: Shao
authors.forename: Guang-Yuan
authors.initials: GY
authors.lastname: Song
authors.forename: Zhen-Yan
authors.initials: ZY
authors.lastname: Zhao
authors.forename: Si-Yong
authors.initials: SY
authors.lastname: Teng
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Wu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000503:physiopathology*; D019308:Palmitic Acid / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation / Q000187:drug effects; D014292:Trimetazidine / Q000494:pharmacology*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D012333:RNA, Messenger; D019308:Palmitic Acid; D044763:Ubiquitin-Conjugating Enzymes; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000098843:Ubiquitin-Conjugating Enzyme UBC9; D014292:Trimetazidine