Article

The Bile Salt Export Pump

Department of Medicine, Institute of Clinical Pharmacology and Toxicology, University Hospital, Zürich, Switzerland.
Pflügers Archiv - European Journal of Physiology (Impact Factor: 3.07). 03/2007; 453(5):611-20. DOI: 10.1007/s00424-006-0152-8
Source: PubMed

ABSTRACT Canalicular secretion of bile salts mediated by the bile salt export pump Bsep constitutes the major driving force for the generation of bile flow. Bsep is a member of the B-family of the super family of ATP-binding cassette transporters and is classified as ABCB11. Bsep has a narrow substrate specificity, which is largely restricted to bile salts. Bsep is extensively regulated at the transcriptional and posttranscriptional level, which directly modulates canalicular bile formation. Pathophysiological alterations of Bsep by either inherited mutations or acquired processes such as inhibition by drugs or disease-related down regulation may lead to a wide spectrum of mild to severe forms of liver disease. Furthermore, many genetic variants of Bsep are known, some of which potentially render individuals susceptible to acquired forms of liver disease.

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    • "Intra-hepatic cholestasis represents a frequent manifestation of DILI in humans (Lee, 2003). In many cases, it results from alterations of the hepatobiliary transporter system, in particular the bile salt export pump (BSEP), which is the most physiologically important canalicular bile transporter (Stieger et al., 2007). Other disturbances, such as altered cell polarity, disruption of cell-to-cell junctions and cytoskeleton disorganization, can also participate in cholestasis. "
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    • "Bile acids are synthesized from cholesterol either by 7a-hydroxylation initiated by cholesterol 7a-hydroxylase or by 27-hydroxylation of cholesterol (Einarsson et al., 2000). Secretion of bile acids from the liver is mediated by the bile salt export pump (BSEP; Stieger et al., 2007). A negative feed-back and a positive feed-forward mechanism, respectively, synchronize and control the transcription of CYP7A1 and BSEP genes. "
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