The bile salt export pump: clinical and experimental aspects of genetic and acquired cholestatic liver disease
- PMID: 20422495
- PMCID: PMC3008346
- DOI: 10.1055/s-0030-1253222
The bile salt export pump: clinical and experimental aspects of genetic and acquired cholestatic liver disease
Abstract
The primary transporter responsible for bile salt secretion is the bile salt export pump (BSEP, ABCB11), a member of the ATP-binding cassette (ABC) superfamily, which is located at the bile canalicular apical domain of hepatocytes. In humans, BSEP deficiency results in several different genetic forms of cholestasis, which include progressive familial intrahepatic cholestasis type 2 (PFIC2), benign recurrent intrahepatic cholestasis type 2 (BRIC2), as well as other acquired forms of cholestasis such as drug-induced cholestasis (DIC) and intrahepatic cholestasis of pregnancy (ICP). Because bile salts play a pivotal role in a wide range of physiologic and pathophysiologic processes, regulation of BSEP expression has been a subject of intense research. The authors briefly describe the molecular characteristics of BSEP and then summarize what is known about its role in the pathogenesis of genetic and acquired cholestatic disorders, emphasizing experimental observations from animal models and cell culture in vitro systems.
Figures


Similar articles
-
Biosynthesis and trafficking of the bile salt export pump, BSEP: therapeutic implications of BSEP mutations.Mol Aspects Med. 2014 Jun;37:3-14. doi: 10.1016/j.mam.2013.05.001. Epub 2013 May 15. Mol Aspects Med. 2014. PMID: 23685087 Free PMC article. Review.
-
Levels of plasma membrane expression in progressive and benign mutations of the bile salt export pump (Bsep/Abcb11) correlate with severity of cholestatic diseases.Am J Physiol Cell Physiol. 2007 Nov;293(5):C1709-16. doi: 10.1152/ajpcell.00327.2007. Epub 2007 Sep 13. Am J Physiol Cell Physiol. 2007. PMID: 17855769
-
The Bile Salt Export Pump: Molecular Structure, Study Models and Small-Molecule Drugs for the Treatment of Inherited BSEP Deficiencies.Int J Mol Sci. 2021 Jan 14;22(2):784. doi: 10.3390/ijms22020784. Int J Mol Sci. 2021. PMID: 33466755 Free PMC article. Review.
-
Genetic determinants of drug-induced cholestasis and intrahepatic cholestasis of pregnancy.Semin Liver Dis. 2010 May;30(2):147-59. doi: 10.1055/s-0030-1253224. Epub 2010 Apr 26. Semin Liver Dis. 2010. PMID: 20422497 Review.
-
Short-chain ubiquitination is associated with the degradation rate of a cell-surface-resident bile salt export pump (BSEP/ABCB11).Mol Pharmacol. 2009 Jan;75(1):143-50. doi: 10.1124/mol.108.049288. Epub 2008 Oct 1. Mol Pharmacol. 2009. PMID: 18829893
Cited by
-
Structural basis of bile salt extrusion and small-molecule inhibition in human BSEP.Nat Commun. 2023 Nov 10;14(1):7296. doi: 10.1038/s41467-023-43109-1. Nat Commun. 2023. PMID: 37949847 Free PMC article.
-
Repeated oral administration of oleanolic acid produces cholestatic liver injury in mice.Molecules. 2013 Mar 7;18(3):3060-71. doi: 10.3390/molecules18033060. Molecules. 2013. PMID: 23470335 Free PMC article.
-
Physiological and molecular biochemical mechanisms of bile formation.World J Gastroenterol. 2013 Nov 14;19(42):7341-60. doi: 10.3748/wjg.v19.i42.7341. World J Gastroenterol. 2013. PMID: 24259965 Free PMC article. Review.
-
Potency of individual bile acids to regulate bile acid synthesis and transport genes in primary human hepatocyte cultures.Toxicol Sci. 2014 Oct;141(2):538-46. doi: 10.1093/toxsci/kfu151. Epub 2014 Jul 23. Toxicol Sci. 2014. PMID: 25055961 Free PMC article.
-
Abnormal Localization of STK17A in Bile Canaliculi in Liver Allografts: An Early Sign of Chronic Rejection.PLoS One. 2015 Aug 25;10(8):e0136381. doi: 10.1371/journal.pone.0136381. eCollection 2015. PLoS One. 2015. PMID: 26305096 Free PMC article.
References
-
- Dean M, Rzhetsky A, Allikmets R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 2001;11(7):1156–1166. - PubMed
-
- Weinman SA, Graf J, Boyer JL. Voltage-driven, taurocholate-dependent secretion in isolated hepatocyte couplets. Am J Physiol. 1989;256(5 Pt 1):G826–G832. - PubMed
-
- Adachi Y, Kobayashi H, Kurumi Y, Shouji M, Kitano M, Yamamoto T. ATP-dependent taurocholate transport by rat liver canalicular membrane vesicles. Hepatology. 1991;14(4 Pt 1):655–659. - PubMed
-
- Müller M, Ishikawa T, Berger U, et al. ATP-dependent transport of taurocholate across the hepatocyte canalicular membrane mediated by a 110-kDa glycoprotein binding ATP and bile salt. J Biol Chem. 1991;266(28):18920–18926. - PubMed