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  • Title: Taurocholate transport by hepatic and intestinal bile acid transporters is independent of FIC1 overexpression in Madin-Darby canine kidney cells.
    Author: Harris MJ, Kagawa T, Dawson PA, Arias IM.
    Journal: J Gastroenterol Hepatol; 2004 Jul; 19(7):819-25. PubMed ID: 15209631.
    Abstract:
    BACKGROUND: Mutations in the human familial intrahepatic cholestasis gene, FIC1, result in progressive familial intrahepatic cholestasis type 1 in children and benign recurrent intrahepatic cholestasis. The present study was performed to determine whether FIC1 transports bile acids and/or influences the activity of apical bile acid transporters. METHODS: The apical secretion assay utilized transfected Madin-Darby canine kidney (MDCK) cells, which stably express the bile acid uptake protein, Na+/taurocholate co-transporting polypeptide (NTCP). These cells were then transiently transfected with FIC1 and/or the bile salt export pump (BSEP) and were grown on Transwell filters to form a polarized monolayer. [(3)H]Taurocholate was added to the basal medium and the taurocholate secretion was measured in the apical medium. A second assay, apical uptake assays, utilized polarized MDCK-II cells, which were transiently transfected with FIC1, FIC1 mutants and/or the apical sodium-dependent bile acid transporter (ASBT). [(3)H]Taurocholate was added to the apical media and intracellular uptake of taurocholate was measured. RESULTS: Apical secretion assays: FIC1 expression in MDCK/NTCP cells had no effect on taurocholate secretion compared to controls. In contrast, apical secretion of taurocholate in BSEP-transfected cells was approximately twofold higher than in non-transfected MDCK/NTCP cells (P < 0.01). The BSEP-mediated secretion was unaffected by co-transfection with FIC1. Apical uptake assays: taurocholate uptake in ASBT expressing cells was 6.5-fold higher than in controls and was unaffected by co-transfection of cells with FIC1 or FIC1 mutants. CONCLUSIONS: These results indicate that FIC1 does not transport taurocholate and, when overexpressed in MDCK cells, had no effect on the function of BSEP or ABST.
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