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The bile salt export pump: molecular properties, function and regulation

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Abstract

Secretion of bile salts from the hepatocyte into bile is the major driving force for the generation of bile flow. Identification of the bile salt export pump (BSEP, ABCB11) as the main adenosine-triphosphate-dependent bile salt transporter in mammalian liver has led to a greater understanding of the biliary bile salt secretory process and its regulation. The biology and pathobiology of BSEP have been the subject of many recent studies. Thus, it has been recognized that while mutations in the gene encoding BSEP are responsible for a subgroup of progressive familial cholestasis (progressive familial intrahepatic cholestasis subtype 2), a pediatric cholestatic disorder that may progress to cirrhosis, defective expression or function of BSEP may underlie some forms of drug-induced cholestasis. The present review summarizes recent data on the molecular properties and regulation of BSEP, as well as the clinical implications of absent or defective function of this hepatic efflux pump.

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Notes

  1. By convention, the names of human hepatobiliary transporter genes are capitalized, whereas rodent genes and their products are written in lower case with capitalization of the first letter. A lower case letter preceding a given transporter indicates rat (r) or mouse (m) protein. In addition, transporter genes are set in italics, whereas gene products are set in roman. A nomenclature scheme of transporters using a ‘stem’ (or ‘root’) symbol for members of a gene family or grouping, with a hierarchical numbering system to distinguish individual members, has been developed by the Human Genome Nomenclature Committee. Guidelines are available at http://www.gene.ucl.ac.uk/nomenclature/guidelines.html

  2. Owing to space constraints, numerous primary references could not be cited directly. We apologize for not being able to pay a proper tribute to those many investigators who are responsible for numerous new discoveries that lead usto a better understanding of bile salt transport by the liver

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Owing to space constraints, numerous primary references could not be cited directly. We apologize for not being able to pay a proper tribute to those many investigators who are responsible for numerous new discoveries that lead usto a better understanding of bile salt transport by the liver

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Acknowledgements

This work was supported by grants from the Fondo Nacional de Ciencia y Tecnología (no. 1020641 and no. 7030025) to Marco Arrese, and from the National Institutes of Health (HD20632) to M. Ananthanrayanan.

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  1. Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, 6510260 , Santiago, Chile

    Marco Arrese

  2. Laboratory of Developmental and Molecular Hepatology, Department of Pediatrics, Mount Sinai School of Medicine, New York, N.Y., USA

    Meenakshisundaram Ananthanarayanan

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Arrese, M., Ananthanarayanan, M. The bile salt export pump: molecular properties, function and regulation. Pflugers Arch - Eur J Physiol 449, 123–131 (2004). https://doi.org/10.1007/s00424-004-1311-4

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