| Characterization of the Role of ABCG2 as a Bile Acid Transporter in Liver and Placenta. | |
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MedLine Citation:
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PMID: 22096226 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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ABCG2 is involved in epithelial transport/barrier functions. Here we have investigated its ability to transport bile acids in liver and placenta. Cholylglycylamido fluorescein (CGamF) was exported by WIF-B9/R cells, which do not express BSEP. Sensitivity to typical inhibitors suggested that CGamF export was mainly mediated by ABCG2. In CHO cells, co-expression of rat Oatp1a1 and human ABCG2 enhanced the uptake and efflux, respectively, of CGamF, cholic acid (CA), glycoCA, tauroCA and taurolithocholic acid-3-sulfate (TLCS). The ability of ABCG2 to export these bile acids was confirmed by microinjecting them together inulin in Xenopus laevis oocytes expressing this pump. ABCG2-mediated bile acid transport was inhibited by estradiol 17β-D-glucuronide and fumitremorgin C. Placental barrier for bile acids accounted for <2-fold increase in fetal cholanemia in spite of >14-fold increased maternal cholanemia induced by obstructive cholestasis in pregnant rats. In rat placenta, the expression of Abcg2, which was much higher than that of Bsep, was not affected by short-term cholestasis. In pregnant rats, fumitremorgin C did not affect uptake/secretion of GCA by the liver but inhibited its fetal-maternal transfer. As compared with wild-type mice, obstructive cholestasis in pregnant Abcg2-/- knockout mice induced similar bile acid accumulation in maternal serum but higher in placenta and fetal serum and liver. In conclusion, ABCG2 is able to transport bile acids. The importance of this function depends on the relative expression in the same epithelium of other bile acid exporters. Thus, ABCG2 may play a key role in bile acid transport in placenta, as BSEP does in liver. |
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Authors:
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Alba M G Blazquez; Oscar Briz; Marta R Romero; Ruben Rosales; Maria J Monte; Javier Vaquero; Rocio I R Macias; Doris Cassio; Jose J G Marin |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-17 |
Journal Detail:
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Title: Molecular pharmacology Volume: - ISSN: 1521-0111 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0035623 Medline TA: Mol Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1 Laboratory of Experimental Hepatology and Drug Targeting, University of Salamanca, CIBERehd, SPAIN; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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