南京农业大学学报2024，Vol.47Issue(1)：28-35,8.DOI:10.7685/jnau.202302003
衣康酸二甲酯对H2O2诱导的AML-12细胞线粒体功能障碍的调节作用及机制研究
The regulatory effect and mechanism of dimethyl itaconate on mitochondrial dysfunction induced by H2 O2 in AML-12 cells
摘要
Abstract
[Objectives]This study aimed to explore the regulatory effect and mechanism of dimethyl itaconate(DMI)on mitochondrial dysfunction in mouse hepatocytes,which will provide a theoretical basis for dimethyl itaconate as a physiological regulator in the prevention of related diseases caused by mitochondrial dysfunction in livestock and poultry.[Methods]The mice hepatocytes(AML-12 cells)were used as the research object in this study.Experimental groups were divided into control group(NC),0.5 mmol·L-1 DMI treatment group,150 μmol·L-1 H2O2 treatment group and 0.5 mmol·L-1 DMI+150 μmol·L-1 H2O2 treatment group.After treatment,the ATP content,mitochondrial DNA(mtDNA)copy number,mitochondrial ROS(mROS)level and mitochondrial membrane potential(MMP)were detected;meanwhile,the AMPK signaling pathway related factors protein level were detected by western blotting.[Results]0.5 mmol·L-1 DMI and 150 μmol·L-1 H2O2 had no significantly effect on the AML-12 cells viability.DMI treatment significantly attenuated H2O2-induced increasing of mROS level and the aberrant decreasing of MMP in AML-12 cells.Meanwhile,we found that the H2O2-stimulated caused decreasing in ATP content and mtDNA levels in AML-12 cells,and DMI treatment obviously inhibited the decreasing of ATP content and mtDNA levels in H2O2-stimulated AML-12 cells.In addition,DMI treatment significantly inhibited the reduction of p-AMPK,SIRT1,PGC-1α,Nrf1,and TFAM protein levels caused by H2O2-stimulation in AML-12 cells(P<0.01),and these effects of DMI were obviously reversed in AML-12 cells pretreated with AMPK inhibitor Compound C.[Conclusions]This study demonstrated that dimethyl itaconate alleviates H2O2-induced mitochondrial dysfunction in AML-12 cells,and these beneficial effects are achieved by activating AMPK-SIRT1-PGC1α signaling axis in hepatocytes.关键词
衣康酸二甲酯/线粒体功能障碍/AMPK-SIRT1-PGC1α信号轴Key words
dimethyl itaconate/mitochondrial dysfunction/AMPK-SIRT1-PGC1α signal axis分类
农业科技引用本文复制引用
闫巍元,张锐,马海田..衣康酸二甲酯对H2O2诱导的AML-12细胞线粒体功能障碍的调节作用及机制研究[J].南京农业大学学报,2024,47(1):28-35,8.基金项目
江苏省高等学校重点学科建设项目 （）
