Toxicoproteomic analysis of phalloidin-induced cholestasis in mouse liver

摘要

Phalloidin induces cholestasis by preventing microfilament depolymerization. Phalloidin has been widely used as an agent to induce intrahepatic cholestasis in experimental animals. The objective of this study was to examine the effects of phalloidin on protein expression profiles in mouse liver, so as to identify potential biomarkers of intrahepatic cholestasis. Phalloidin was administered to BALB/c mice at a predetermined dose of 1 mg/kg for 7 days, and phalloidin-induced cholestasis was observed. Hepatic protein expression was investigated via two-dimensional (2D) electrophoresis, and 21 protein spots showing significantly different expression between the treated and control groups were excised from the gels and identified by MALDI-TOF/TOF. The identified proteins were involved in cytoskeletal changes, lipid metabolism, gluconeogenesis, detoxification, and transport mechanisms. Among these proteins, the up-regulation of HSP90-β in phalloidin-treated mice was confirmed by Western blot analysis and then by RT-PCR, indicating that it may serve as a useful biomarker of cholestasis. In summary, these results provide insight into the mechanism involved in phalloidin-induced cytoskeletal change and cholestasis.