Effect and mechanism of NAD-dependent protein deacetylase Sirtuin-3 on diabetic cardiomyopathy
Objective To investigate the effect of NAD-dependent protein deacetylase Sirtuin-3(Sirt3)on diabetic cardiomyopathy(DCM)and its related mechanism.Methods Six 8-week-old male C57BL/6J mice were divided into normal group and DCM model group,with 3 mice in each group.Mice in DCM model group were intraperitoneally injected streptorea for 5 days after 4 weeks of high-fat diet.Mice in the normal group were fed normal diet and injected with the same amount of citrate buffer intraperitoneally for 5 days.H9C2 cells were stimulated with 300 μmol/L palmitic acid(PA)for 24 hours to establish a cardiomyocyte lipid toxicity model.Pa-trea-ted cells were included in the PA group and untreated cells in the control group.Cells were transfected with Sirt3 interfering RNA(si-Sirt3)and control reagent(si-con).After transfection for 24 hours,the cells were stimulated by PA for 24 hours and collected.The cells were divided into four groups according to different treatment methods:si-con group,si-Sirt3 group,si-con+PA group,and si-Sirt3+PA group.Western blot was used to detect Sirt3 protein levels in myocardial tissue of mice in normal group and DCM model group,and Sirt3 protein levels in cells of control group and PA group.The level of superoxide dismutase 2(SOD2)acetylation in H9C2 cells was detected by Western blot.The production of reactive oxygen species was detected by DHE staining.Results Compared with normal group,the level of Sirt3 protein in myocardial tissue of mice in DCM model group was decreased,and the difference was statistically significant(P<0.05).Compared with control group,the Sirt3 protein level in PA group was decreased,and the difference was statisti-cally significant(P<0.05).Compared with si-con group,ac-SOD2/SOD2 level and reactive oxygen species level in si-con+PA group were increased,and the difference was statistically significant(P<0.05).Compared with si-con+PA group,ac-SOD2/SOD2 level and reactive oxygen species level in si-Sirt3+PA group were increased,and the difference was statistically significant(P<0.05).Conclu-sion Sirt3 can eliminate reactive oxygen species in cardiomyocytes through the deacetylation of SOD2,reduce oxidative stress damage in cardiomyocytes,and play an important role in the occurrence and development of DCM.
NAD-dependent protein deacetylase Sirtuin-3Diabetic cardiomyopathyOxidative stressReactive oxygen spe-ciesPalmitic acid
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