Résumé
Objective To investigate sodium hydrogen sulfide(NaHS)with function of regulating glutathione(GSH)synthesis to reduce reactive oxygen species(ROS)production in type 2 diabetic cardiomyopathy(DCM).Methods Mouse cardiomyocyte cell line HL-1 was incubated with high concentration of glucose(HG:40 mmol/L)and palmitate(Pal:500 μmol/L)as a cell model of type 2 DCM.HL-1 cells were incubated with NaHS(100 μmol/L),DL-propargylglycin(PPG,1 mmol/L)and N-acetyl-l-cysteine(NAC,5 mmol/L),respectively for 72 hours.The expression of cystathionine-γ-lyase(CSE)and the key enzymes of glutathione production was tested by Western blot.Dihydroethidium(DHE)and dichlorofluoromethane(DCFH)were used to detect the content of ROS in HL-1 cells.Cell viability was detected by CCK8 kit.The content of total GSH was detected.The interaction between muscle specific ring finger protein 1(Murf1)and nuclear factor erythroid-derived 2-related factor 2(Nrf2)and Nrf2 ubiquitylation was determined by co-immunoprecipitation(co-IP).Results Compared with control group,the expression level of CSE,solute carrier family 7 members 11(SLC7A11),glutamate cysteine ligase C(GCLC),glutamate cysteine ligase M(GCLM)and glutathione synthetase(GSS)in HL-1 cells treated incubated with high glucose and palmitate was decreased,however,NaHS was found to restore it.NaHS reduced the content of ROS in HL-1 cells treated with high glucose and palmitate.The interaction between murf1 and Nrf2 was confirmed by co-immunoprecipitation(Co-IP).Compared with NaHS group,the ubiquitylation level of Nrf2 was enhanced in high glucose and palmitate group.Conclusions Sodium hydrosulfide may reduce the ubiquitylation level of Nrf2 and promote the expression of key enzymes of GSH synthesis.
Résumé
Objective To investigate the function of sodium hydrosulfide(NaHS)to regulate mitochondrial fusion/fission in diabetic cardiomyopathy and underlying mechanism.Methods Db/db mice as type 2 diabetes animal model were treated by NaHS.H9C2 cells incubated with glucose(40 mmol/L),palmitic acid(200 μmol/L,Pal)and oleate(200 μmol/L,Ole)were intervened by NaHS(100 μmol/L).H2C9 cellswere divided into control,HG+Pal+Ole,HG+Pal+Ole+NaHS and Pal+Ole+DJ-1 siRNA+NaHS groups.The protein level of Mfn2,Fis1,CSE,and DJ-1 was determined by Western blot.Mitotracker staining was used to observe the morphology of mitochondria.The ultra-structural alteration of cardiac tissues was detected by transmission electron microscopy.The cardiac functions were detected by echocardiography.Results Expression of Fis1 was increased(P＜0.05)and expression of Mfn2 was decreased(P＜0.05)in db/db and H9C2 treated by HG+Pal+Ole compared to control group.NaHS could upregulate the expression DJ-1,enhance the expression of Mfn2,and reduce the expression of Fis1.In db/db mice,cardiac systolic function was reduced.Disordered arrangement of myofilament,loss of cristae and mitochondrial fission were observed.NaHS could ameliorate these alterations.Conclusions NaHS may alleviate mitochondria injury by promoting mitochondrial fusion.
Résumé
In 84 elderly type 2 diabetic patients, the urinary albumin excretion rate was positively correlated with left ventricular inner diameter and left ventricular mass, and negatively with left ventricular ejection fracton.