A dynamic plasma membrane proteome analysis of alcohol-induced liver cirrhosis

Abstract

Alcohol-induced injury has become one of the major causes for liver cirrhosis. However, the molecular mechanisms of ethanol-induced injury are not fully understood. To this end, we performed a dynamic plasma membrane proteomic research on rat model. A rat model from hepatitis to liver cirrhosis was developed. Plasma membrane from liver tissue with liver fibrosis stage of 2 and 4 (S2 and S4) was purified by sucrose density gradient centrifugation. Its purification was verified by western blotting. Proteins from plasma membrane were separated by two-dimensional electrophoresis (2DE) and differentially expressed proteins were identified by tandem mass spectrometry. 16 consistent differentially expressed proteins from S2 to S4 were identified by mass spectrometry. The expression of differentially expressed proteins annexin A6 and annexin A3 were verified by western blotting, and annexin A3 was futher verified by immunohistochemistry. Our research suggests a possible mechanism by which ethanol alters protein expression to enhance the liver fibrosis progression. These differentially expressed proteins might be new drug targets for treating alcoholic liver cirrhosis.

Hepatic proteomic analysis revealed altered metabolic pathways in insulin resistant Akt1 +/− /Akt2 −/− mice

“…In our study, annexin A5 was shown to be upregulated and annexin A6 was shown to be downregulated. Other proteomic studies in models of insulin resistance and liver injury have demonstrated similar changes with regards to abundance and direction of change of these annexins [45-48]. Phenazine biosynthesis-like domain-containing protein 2, found to be of decreased abundance in the AKT1 +/- /AKT2 -/- - mice in our dataset, has previously been detected at reduced levels in hepatocellular tumors [49].…”

Annexin A6 protein is downregulated in human hepatocellular carcinoma

“…In rats suffering from advanced alcoholic liver cirrhosis, AnxA6 is reduced in the plasma membrane fraction of the liver [23]. Together with the diverse roles of AnxA6 in pathways relevant in liver physiology and its regulation by adiponectin, this suggested that AnxA6 levels may also be affected in liver diseases of different etiologies, and prompted us to analyze AnxA6 levels in NAFLD and HCC.…”