Influence of SRT1720 on apoptosis ofhigh glucose-induced mouse mesangial cells / 中国药理学通报

ABSTRACT

Aim To investigate the effect of Sirt1 activator SRT1720 on high glucose(HG)-induced apoptosis in mouse mesangial cells(MMCs).Methods Cultured mouse MMCs were divided into normal glucose group(NG),NG plus mannitol group(M),high glucose group(HG),HG plus SRT1720 group(HG+SRT).Apoptosis of MMCs was analyzed by DeadEndTM Fluorometric TUNEL System and flow cytometry.Reactive oxygen species(ROS)production was observed by flow cytometry.The expression levels of caspase-3,cleaved caspase-3,Bax,Bcl-2,p38 MAPK,p-p38 MAPK,p53,acetylated p53 and cytochrome C protein were observed by Western blot.The mRNA levels of Bax and Bcl-2 were detected by real-time PCR.Results Compared with normal glucose group,the production of ROS,the number of cell apoptosis,the expression of cleaved caspase-3,p-p38 MAPK and acetylated p53 and ratio of Bax/Bcl-2 were significantly increased,the expression of Sirt1 was decreased,meanwhile,the release of cytochrome C from mitochondria to cytoplasm was significantly increased in MMCs in high glucose group.Treatment with SRT1720 inhibited HG-induced increase of ROS production,cell apoptosis,expression of cleaved caspase-3,acetylated p53 and p-p38 MAPK,ratio of Bax/Bcl-2 and release of cytochrome C,and reversed HG-induced Sirt1 expression.Conclusion SRT1720 could prevent HG-induced apoptosis maybe by decreasing ROS production,preserving mitochondrial function and inhibiting p53 acetylation and activation of p38 MAPK in MMCs.