Hepatic expression of detoxification enzymes is decreased in human obstructive cholestasis due to gallstone biliary obstruction

• Published in: PloS one 2015-03, Vol.10 (3), p.e0120055-e0120055
• Main Authors: Chai, Jin, Feng, Xinchan, Zhang, Liangjun, Chen, Sheng, Cheng, Ying, He, Xiaochong, Yang, Yingxue, He, Yu, Wang, Huaizhi, Wang, Rongquan, Chen, Wensheng
• Format: Article
• Language: English
• Subjects: Acids; Bile; Cholestasis; Cholestasis - enzymology; Cholestasis - etiology; Cholestasis - genetics; Cholestasis - metabolism; Cytochrome P-450; Deoxycholic acid; Detoxification; Disease control; Enzymes; Gallstones; Gallstones - complications; Gene Expression Regulation, Enzymologic; GSTM1 protein; Human behavior; Human performance; Humans; Liver; Liver - enzymology; Liver diseases; Membrane Transport Proteins - genetics; Molecular modelling; Nuclear receptors; Patients; Receptors; Receptors, Cytoplasmic and Nuclear - genetics; RNA; Rodents; Transcription factors; Transcription Factors - genetics; Up-Regulation; Vitamin D receptors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0120055

Levels of bile acid metabolic enzymes and membrane transporters have been reported to change in cholestasis. These alterations (e.g. CYP7A1 repression and MRP4 induction) are thought to be adaptive responses that attenuate cholestatic liver injury. However, the molecular mechanisms of these adaptive responses in human obstructive cholestasis due to gallstone biliary obstruction remain unclear. We collected liver samples from cholestatic patients with biliary obstruction due to gallstones and from control patients without liver disease (n = 22 per group). The expression levels of bile acid synthetic and detoxification enzymes, membrane transporters, and the related nuclear receptors and transcriptional factors were measured. The levels of bile acid synthetic enzymes, CYP7B1 and CYP8B1, and the detoxification enzyme CYP2B6 were increased in cholestatic livers by 2.4-fold, 2.8-fold, and 1.9-fold, respectively (p