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Abstract Title:

Rg3 promotes the SUMOylation of SERCA2a and corrects cardiac dysfunction in heart failure.

Abstract Source:

Pharmacol Res. 2021 Aug 21 ;172:105843. Epub 2021 Aug 21. PMID: 34428586

Abstract Author(s):

Zhihao Liu, Xiyun Bian, Wenbo Gao, Jing Su, Chuanrui Ma, Xiaolin Xiao, Tian Yu, Han Zhang, Xiaozhi Liu, Guanwei Fan

Article Affiliation:

Zhihao Liu

Abstract:

SUMOylation of sarcoplasmic/endoplasmic reticulum CaATPase 2a (SERCA2a) has been shown to play a critical role in the abnormal Cacycle of heart failure. Ginsenoside Rg3 (Rg3), the main active constituent of Panax ginseng, exerts a wide range of pharmacological effects in cardiovascular diseases. However, the effect of Rg3 on abnormal Cahomeostasis in heart failure has not been reported. In this study, we showed a novel role of Rg3 in the abnormal Cacycle in cardiomyocytes of mice with heart failure. Among mice undergoing transverse aortic constriction, animals that received Rg3 showed improvements in cardiac function and Cahomeostasis, accompanied by increases in the SUMOylation level and SERCA2a activity. In an isoproterenol (ISO)-induced cell hypertrophy model, Rg3 reduced the ISO-induced Caoverload in HL-1 cells. Gene knockout of SUMO1 in mice inhibited the cardioprotective effect of Rg3, and SUMO1 knockout mice that received Rg3 did not exhibit improved Cahomeostasis in cardiomyocytes. Additionally, mutation of the SUMOylation sites of SERCA2a blocked the positive effect of Rg3 on the ISO-induced abnormal Cacycle in HL-1 cells, and was accompanied by an abnormal endoplasmic reticulum stress response and generation of ROS. Our data demonstrated that Rg3 has a positive effect on the abnormal Cacycle in the cardiomyocytes of mice with heart failure. SUMO1 is an important factor that mediates the protective effect of Rg3. Our findings suggest that drug intervention by regulating the SUMOylation of SERCA2a can provide a novel therapeutic strategy for the treatment of heart failure.

Study Type : Animal Study

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