Original ArticleThe Expression of Ubc9 and the Intensity of SERCA2a-SUMOylation Were Reduced in Diet-induced Obese Rats and Partially Restored by TrimetazidineYao, Jing MD; Shao, Xing-Hui MD; Song, Guang-Yuan MD, PhD; Zhao, Zhen-Yan MD; Teng, Si-Yong MD, PhD; Wu, Yong-Jian MD, PhDAuthor Information 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. Reprints: Yong-Jian Wu, MD, PhD, Department of Coronary Heart Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing, 100037, People's Republic of China (e-mail: email@example.com). Supported by the Postgraduate Innovative Foundation of Peking Union Medical College (grant number: 2012-1002-30) and the Doctoral Scientific Fund of the Ministry of Education of China (grant number: 20121106110010). The authors report no conflicts of interest. Received June 01, 2014 Accepted August 10, 2014 Journal of Cardiovascular Pharmacology: January 2015 - Volume 65 - Issue 1 - p 47-53 doi: 10.1097/FJC.0000000000000162 Buy Metrics 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. Method and 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. © 2015 by Lippincott Williams & Wilkins.