Protein acetylation in mitochondria plays critical functions in the pathogenesis of fatty liver disease.

BACKGROUND: Fatty liver is a high incidence of perinatal disease in dairy cows caused by negative energy balance, which seriously threatens the postpartum health and milk production. It has been reported that lysine acetylation plays an important role in substance and energy metabolism. Predictably, most metabolic processes in the liver, as a vital metabolic organ, are subjected to acetylation. Comparative acetylome study were used to quantify the hepatic tissues from the severe fatty liver group and normal group. Combined with bioinformatics analysis, this study provides new insights for the role of acetylation modification in fatty liver disease of dairy cows. RESULTS: We identified 1841 differential acetylation sites on 665 proteins. Among of them, 1072 sites on 393 proteins were quantified. Functional enrichment analysis shows that higher acetylated proteins are significantly enriched in energy metabolic pathways, while lower acetylated proteins are significantly enriched in pathways related to immune response, such as drug metabolism and cancer. Among significantly acetylated proteins, many mitochondrial proteins were identified to be interacting with multiple proteins and involving in lipid metabolism. Furthermore, this study identified potential important proteins, such as HADHA, ACAT1, and EHHADH, which may be important regulatory factors through modification of acetylation in the development of fatty liver disease in dairy cows and possible therapeutic targets for NAFLD in human beings. CONCLUSION: This study provided a comprehensive acetylome profile of fatty liver of dairy cows, and revealed important biological pathways associated with protein acetylation occurred in mitochondria, which were involved in the regulation of the pathogenesis of fatty liver disease. Furthermore, potential important proteins, such as HADHA, ACAT1, EHHADH, were predicted to be essential regulators during the pathogenesis of fatty liver disease. The work would contribute to the understanding the pathogenesis of NAFLD, and inspire in the development of new therapeutic strategies for NAFLD.

Effect of allicin on proliferation and apoptosis of KG-1 cells and its molecular mechanism / 中国中药杂志

Allicin is one of the main bioactive substances in garlic, with antibacterial, hypolipidemic and other pharmacological effects. In this study, apoptosis-related indicators were detected to explore the molecular mechanism of allicin on KG-1 cell proliferation inhibition. The apoptosis rate of KG-1 cells induced by allicin was detected by flow cytometry. The effect of allicin on the expressions of Bax, Bcl-2, survivin and ERK mRNA in KG-1 cells was detected by RT-qPCR. Western blot was used to detect the expressions of caspase 3, cleaved caspase 3, ERK1/2, p-ERK1/2 and survivin protein in KG-1 cells. According to the findings, compared with the control group, allicin could significantly inhibit the proliferation activity of KG-1 cells in a concentration-dependent and time-dependent manner. Flow cytometry showed that allicin could induce the apoptosis of KG-1 cells, which was mainly late apoptosis. The results of RT-qPCR showed that the expressions of Bax mRNA, Bcl-2, survivin and ERK mRNA in KG-1 cells increased after treatment with allicin. The results of Western-blot showed that after KG-1 cells were treated with allicin, the expressions of caspase 3 and its active form cleaved caspase 3 increased, the expressions of survivin, ERK1/2 and its active form p-ERK1/2 were decreased, of which p-ERK1/2 was down-regulated in a dose-dependent manner. The above results suggest that allicin inhibited the proliferation of KG-1 cells primarily by inducing late apoptosis; the execution of apoptosis involved cleaved caspase 3; the induction of apoptosis involved the protein expression, the decrease of ERK1/2andexpression of survivin and the dose-dependent decrease of p-ERK1/2; the mRNA expression involved the increase of Bax, and the down-regulation of survivin, Bcl-2 and ERK1/2.