Sphingosine 1 phosphate receptor-1 （S1PR1） signaling protects cardiac function by inhibiting cardiomyocyte autophagy  

作　　者：Yong-Zeng CHEN Fan WANG Hai-Jun WANG Hong-Bin LIU 

机构地区：[1]Department of Geriatric Cardiology, Chinese People's Liberation Army General Hospital, Beijing, China

出　　处：《Journal of Geriatric Cardiology》2018年第5期334-345,共12页老年心脏病学杂志（英文版）

摘　　要：Objective To investigate the role of sphingosine-l-phosphate （S1P） and its receptors in cardiomyocyte autophagy, cardiomyocyte hypertrophy and cardiac function. Methods Cardiomyocytes were isolated from neonatal Vista rats. Autophagy and hypertrophy of car- diomyocytes were induced via starvation culture and phenylephrine （PE）, respectively, and S 1 P was used to treat the cardiomyocytes. The effect of S1P on cardiomyocyte autophagy was evaluated by the number of autophagosomes, the expression of autophagy-related proteins and autophagic marker genes in cardiomyocytes. The effect of S1P on cardiomyocyte hypertrophy was evaluated by examining the surface area of cardiomyoeytes and the expression of hypertrophic genes. Subsequently, different small interfering RNAs （siRNAs） were used to knockdown the expression of the three types of S 1P receptors on cardiomyocytes and to analyze the type of receptor that mediates S 1P sig- naling in cardiomyocytes. Finally, sphingosine 1 phosphate receptor-1 （S1PR1） was knockout in the mouse cardiomyocytes using the Cas9 technique. The effect of S 1PR1 on cardiac autophagy and cardiac hypertrophy was examined by assessing cardiomyocyte autophagy, car- diomyocyte hypertrophy and cardiac function. Results Starvation-induced cardiomyocyte autophagy and PE -induced cardiomyocyte hy- pertrophy were significantly attenuated by SIP. The results showed that the formation of autophagosomes was decreased, the auto- phagy-associated protein LC3 II/I and the expression of autophagic marker genes Atg5, Atgl2, Beclinl and LC3B decreased after SIP treatment. The surface area of the cardiomyocytes was decreased, and the expression of hypertrophic genes, including atrial natriuretic factor （ANF）, skeletal muscle and cardiac actin （SKA）, myosin heavy chain （β-MHC） and brain natriuretic peptide （BNP） were all decreased after S 1 P treatment. The autophagy and hypertrophy of cardiomyocytes in the S 1PR 1 knocked-down group were significantly increased compared to thos

关 键 词：AUTOPHAGY CARDIOMYOCYTE HYPERTROPHY S1PR1 

分 类 号：Q463[生物学—生理学] O629.11[理学—有机化学]