关键词: 糖尿病心肌病, 硫化氢, 谷胱甘肽, 核因子红细胞系2相关因子2(Nrf2), E3连接酶肌环指蛋白-1(Murf1)

Abstract: 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.

Key words: diabetic cardiomyopathy, hydrogen sulfide, glutathione, nuclear factor erythroid-derived 2-related factors 2(Nrf2), muscle specific ring finger protein 1(Murf1)