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Research ArticleSpecial Section on Transporters in Toxicity and Disease

The Role of Canalicular ABC Transporters in Cholestasis

Frans J. C. Cuperus, Thierry Claudel, Julien Gautherot, Emina Halilbasic and Michael Trauner
Drug Metabolism and Disposition April 2014, 42 (4) 546-560; DOI: https://doi.org/10.1124/dmd.113.056358
Frans J. C. Cuperus
Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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Thierry Claudel
Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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Julien Gautherot
Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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Emina Halilbasic
Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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Michael Trauner
Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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Abstract

Cholestasis, a hallmark feature of hepatobiliary disease, is characterized by the retention of biliary constituents. Some of these constituents, such as bile acids, inflict damage to hepatocytes and bile duct cells. This damage may lead to inflammation, fibrosis, cirrhosis, and eventually carcinogenesis, sequelae that aggravate the underlying disease and deteriorate clinical outcome. Canalicular ATP-binding cassette (ABC) transporters, which mediate the excretion of individual bile constituents, play a key role in bile formation and cholestasis. The study of these transporters and their regulatory nuclear receptors has revolutionized our understanding of cholestatic disease. This knowledge has served as a template to develop novel treatment strategies, some of which are currently already undergoing phase III clinical trials. In this review we aim to provide an overview of the structure, function, and regulation of canalicular ABC transporters. In addition, we will focus on the role of these transporters in the pathogenesis and treatment of cholestatic bile duct and liver diseases.

Footnotes

    • Received November 30, 2013.
    • Accepted January 28, 2014.
  • This work was supported by funding from the Austrian Science Fund (FWF) project “Transmembrane Transporters in Health and Disease” [Grant SFBF35].

  • Please note that abbreviations for transporters and nuclear receptors were capitalized throughout this article when symbols were identical for human and rodents.

  • dx.doi.org/10.1124/dmd.113.056358.

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 42 (4)
Drug Metabolism and Disposition
Vol. 42, Issue 4
1 Apr 2014
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Research ArticleSpecial Section on Transporters in Toxicity and Disease

ABC Transporters and Cholestasis

Frans J. C. Cuperus, Thierry Claudel, Julien Gautherot, Emina Halilbasic and Michael Trauner
Drug Metabolism and Disposition April 1, 2014, 42 (4) 546-560; DOI: https://doi.org/10.1124/dmd.113.056358

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Research ArticleSpecial Section on Transporters in Toxicity and Disease

ABC Transporters and Cholestasis

Frans J. C. Cuperus, Thierry Claudel, Julien Gautherot, Emina Halilbasic and Michael Trauner
Drug Metabolism and Disposition April 1, 2014, 42 (4) 546-560; DOI: https://doi.org/10.1124/dmd.113.056358
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  • Article
    • Abstract
    • Introduction
    • Bile Acid Metabolism and Its Regulation
    • ABCB11
    • ABCC2
    • ABCB1
    • ABCG2
    • ABCB4
    • ABCG5/8
    • Canalicular ABC Transporters and Their Regulatory NRs as Drug Targets
    • Conclusion and Perspectives
    • Authorship Contributions
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