Bile salt export pump (BSEP/ABCB11): Trafficking and sorting disturbances

Current Molecular Pharmacology

Volumn 6, Issue 2, 2013, Pages 95-103

  Hayashi, Hisamitsu ^a   Sugiyama, Yuichi ^b  

^a UNIVERSITY OF TOKYO   (Japan)

^b RIKEN   (Japan)

Author keywords

Atp binding cassette (ABC) transporters; Bile acid; Bile formation; Bile salt export pump (BSEP); Cholestasis; Protein degradation; Protein trafficking

Indexed keywords

4 PHENYLBUTYRIC ACID; ABC TRANSPORTER; BILE SALT; BILE SALT EXPORT PUMP; CHOLERETIC AGENT; SILIBININ; UNCLASSIFIED DRUG; URSODEOXYCHOLIC ACID;

ARTICLE; BILIARY EXCRETION; GENE MUTATION; HUMAN; INTRAHEPATIC CHOLESTASIS; LIVER CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN GLYCOSYLATION; PROTEIN SYNTHESIS; TOXIC HEPATITIS;

EID: 84882769690     PISSN: 18744672     EISSN: 18744702     Source Type: Journal    
DOI: 10.2174/18744672113069990036     Document Type: Article

References (81)

1. Boyer J.L., Sperber I. Secretion of organic anions in the formation of urine and bile [Pharmacol. Rev. 1959;11:109-134]. J. Hepatol., 2002, 36, 4-7.
2. Sperber I. Secretion of organic anions in the formation of urine and bile. Pharmacol. Rev., 1959, 11, 109-134.
3. Kullak-Ublick, G.A.; Stieger, B.; Meier, P.J. Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology, 2004, 126, 322-342.
4. Trauner, M.; Boyer, J.L. Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev., 2003, 83, 633-671.
5. Boyer, J.L.; Ng, O.C.; Ananthanarayanan, M.; Hofmann, A.F.; Schteingart, C.D.; Hagenbuch, B.; Stieger, B.; Meier, P.J. Expression and characterization of a functional rat liver Na+ bile acid cotransport system in COS-7 cells. Am. J. Physiol., 1994, 266, G382-G387.
6. Hagenbuch, B.; Stieger, B.; Foguet, M.; Lubbert, H.; Meier, P.J. Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system. Proc. Natl. Acad. Sci. USA, 1991, 88,10629-10633.
7. Wolkoff, A.W.; Cohen, D.E. Bile acid regulation of hepatic physiology: I. Hepatocyte transport of bile acids. Am. J. Physiol. Gastrointest. Liver Physiol., 2003, 284, G175-G179.
8. Gerloff, T.; Stieger, B.; Hagenbuch, B.; Madon, J.; Landmann, L.; Roth, J.; Hofmann, A.F.; Meier, P.J. The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. J. Biol. Chem., 1998, 273, 10046-10050.
9. Jansen, P.L.; Strautnieks, S.S.; Jacquemin, E.; Hadchouel, M.; Sokal, E.M.; Hooiveld, G.J.; Koning, J.H.; De Jager-Krikken, A.; Kuipers, F.; Stellaard, F.; Bijleveld, C.M.; Gouw, A.; Van Goor, H.; Thompson, R.J.; Müller, M. Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis. Gastroenterology, 1999,117, 1370-1379.
10. Strautnieks, S.S.; Bull, L.N.; Knisely, A.S.; Kocoshis, S.A.; Dahl, N.; Arnell, H.; Sokal, E.; Dahan, K.; Childs, S.; Ling, V.; Tanner, M.S.; Kagalwalla, A.F.; Németh, A.; Pawlowska, J.; Baker, A.; Mieli-Vergani, G.; Freimer, N.B.; Gardiner, R.M.; Thompson, R.J. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat. Genet., 1998, 20, 233-238.
11. Kuipers, F.; Enserink, M.; Havinga, R.; van der Steen, A.B.; Hardonk, M.J.; Fevery, J.; Vonk, R.J. Separate transport systems for biliary secretion of sulfated and unsulfated bile acids in the rat. J. Clin. Invest., 1988, 81, 1593-1599.
12. Takikawa, H.; Sano, N.; Narita, T.; Uchida, Y.; Yamanaka, M.; Horie, T.; Mikami, T.; Tagaya, O. Biliary excretion of bile acid conjugates in a hyperbilirubinemic mutant Sprague-Dawley rat. Hepatology, 1991, 14, 352-360.
13. Keppler, D.; Konig, J. Hepatic secretion of conjugated drugs and endogenous substances. Semin. Liver Dis., 2000, 20, 265-272.
14. Green, R.M.; Hoda, F.; Ward, K.L. Molecular cloning and characterization of the murine bile salt export pump. Gene, 2000, 241, 117-123.
15. Noe, J.; Hagenbuch, B.; Meier, P.J.; St-Pierre, M.V. Characterization of the mouse bile salt export pump overexpressed in the baculovirus system. Hepatology, 2001, 33, 1223-1231.
16. Childs, S.; Yehm R.L.; Georges, E.; Ling, V. Identification of a sister gene to P-glycoprotein. Cancer Res., 1995, 55, 2029-2034.
17. Stieger, B.; O'Neill, B.; Meier, P.J. ATP-dependent bile-salt transport in canalicular rat liver plasma-membrane vesicles. Biochem. J., 1992, 284(Pt. 1), 67-74.
18. Byrne, J.A.; Strautnieks, S.S.; Mieli-Vergani, G.; Higgins, C.F.; Linton, K.J.; Thompson, R.J. The human bile salt export pump: characterization of substrate specificity and identification of inhibitors. Gastroenterology, 2002, 123, 1649-1658.
19. Hayashi, H.; Takada, T.; Suzuki, H.; Onuki, R.; Hofmann, A.F.; Sugiyama, Y. Transport by vesicles of glycine- and taurine-conjugated bile salts and taurolithocholate 3-sulfate: a comparison of human BSEP with rat Bsep. Biochim. Biophys. Acta, 2005, 1738, 54-62.
20. Noe, J.; Stieger, B.; Meier, P.J. Functional expression of the canalicular bile salt export pump of human liver. Gastroenterology, 2002, 123, 1659-1666.
21. Hirano, M.; Maeda, K.; Hayashi, H.; Kusuhara, H.; Sugiyama, Y. Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin. J. Pharmacol. Exp. Ther., 2005, 314, 876-882.
22. Childs, S.; Yeh, R.L.; Hui, D.; Ling, V. Taxol resistance mediated by transfection of the liver-specific sister gene of P-glycoprotein. Cancer Res., 1998, 58, 4160-4167.
23. Lecureur, V.; Sun, D.; Hargrove, P.; Schuetz, E.G.; Kim, R.B.; Lan, L.B.; Schuetz, J.D. Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein. Mol. Pharmacol., 2000, 57, 24-35.
24. Strautnieks, S.S.; Byrne, J.A.; Pawlikowska, L.; Cebecauerova, D.; Rayner, A.; Dutton, L.; Meier, Y.; Antoniou, A.; Stieger, B.; Arnell, H.; Ozçay, F.; Al-Hussaini, H.F.; Bassas, A.F.; Verkade, H.J.; Fischler, B.; Németh, A.; Kotalová, R.; Shneider, B.L.; Cielecka-Kuszyk, J.; McClean, P.; Whitington, P.F.; Sokal, E.; Jirsa, M.; Wali, S.H.; Jankowska, I.; Pawlowska, J.; Mieli-Vergani, G.; Knisely, A.S.; Bull, L.N.; Thompson, R.J. Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families. Gastroenterology, 2008, 134, 1203-1214.
25. Wang, L.; Soroka, C.J.; Boyer, J.L. The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II. J. Clin. Invest., 2002, 110, 965-972.
26. Hayashi, H.; Takada, T.; Suzuki, H.; Akita, H.; Sugiyama, Y. Two common PFIC2 mutations are associated with the impaired membrane trafficking of BSEP/ABCB11. Hepatology, 2005, 41, 916-924.
27. Plass, J.R.; Mol, O.; Heegsma, J.; Geuken, M.; de Bruin, J.; Elling, G.; Muller, M.; Faber, K.N.; Jansen, P.L. A progressive familial intrahepatic cholestasis type 2 mutation causes an unstable, temperature-sensitive bile salt export pump. J. Hepatol, 2004, 40, 24-30.
28. Hayashi, H.; Sugiyama, Y. 4-phenylbutyrate enhances the cell surface expression and the transport capacity of wild-type and mutated bile salt export pumps. Hepatology, 2007, 45, 1506-1516.
29. Kubitz, R.; Keitel, V.; Scheuring, S.; Kohrer, K.; Haussinger, D. Benign recurrent intrahepatic cholestasis associated with mutations of the bile salt export pump. J. Clin. Gastroenterol, 2006, 40, 171-175.
30. van Mil, S.W.; van der Woerd, W.L.; van der Brugge, G.; Sturm, E.; Jansen, P.L.; Bull, L.N.; van den Berg, IE, Berger, R.; Houwen, R.H.; Klomp, L.W. Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11. Gastroenterology, 2004, 127, 379-384.
31. Stieger, B. Role of the bile salt export pump, BSEP, in acquired forms of cholestasis. Drug Metab. Rev., 2010, 42, 437-445.
32. Kagawa, T.; Watanabe, N.; Mochizuki, K.; Numari, A.; Ikeno, Y.; Itoh, J.; Tanaka, H.; Arias, I.M.; Mine, T. Phenotypic differences in PFIC2 and BRIC2 correlate with protein stability of mutant Bsep and impaired taurocholate secretion in MDCK II cells. Am. J. Physiol. Gastrointest. Liver Physiol., 2008, 294, G58-G67.
33. Lam, P.; Pearson, C.L.; Soroka, C.J.; Xu, S.; Mennone, A.; Boyer, J.L. 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, 293, C1709-C1716.
34. Noe, J.; Kullak-Ublick, G.A.; Jochum, W.; Stieger, B.; Kerb, R.; Haberl, M.; Mullhaupt, B. et al. Impaired expression and function of the bile salt export pump due to three novel ABCB11 mutations in intrahepatic cholestasis. J. Hepatol., 2005, 43, 536-543.
35. Pauli-Magnus, C.; Meier, P.J.; Stieger, B. Genetic determinants of drug-induced cholestasis and intrahepatic cholestasis of pregnancy. Semin. Liver Dis., 2010, 30, 147-159.
36. Bossard, R.; Stieger, B.; O'Neill, B.; Fricker, G.; Meier, P.J. Ethinylestradiol treatment induces multiple canalicular membrane transport alterations in rat liver. J. Clin. Invest., 1993, 91, 2714-2720.
37. Lee, J.M.; Trauner, M.; Soroka, C.J.; Stieger, B.; Meier, P.J.; Boyer, J.L. Expression of the bile salt export pump is maintained after chronic cholestasis in the rat. Gastroenterology, 2000, 118, 163-172.
38. Micheline, D.; Emmanuel, J.; Serge, E. Effect of Ursodeoxycholic Acid on the Expression of the Hepatocellular Bile Acid Transporters (Ntcp and bsep) in Rats With Estrogen-Induced Cholestasis. J. Pediatr. Gastroenterol. Nutr., 2002, 35, 185-191.
39. Crocenzi, F.A.; Mottino, A.D.; Cao, J.; Veggi, L.M.; Pozzi, E.J.; Vore, M.; Coleman, R.; Roma, M.G. Estradiol-17beta-D-glucuronide induces endocytic internalization of Bsep in rats. Am. J. Physiol. Gastrointest. Liver Physiol., 2003, 285, G449-G459.
40. Crocenzi, F.A.; Sanchez, Pozzi E.J.; Ruiz, M.L.; Zucchetti, A.E.; Roma, M.G.; Mottino, A.D.; Vore, M. Ca(2+)-dependent protein kinase C isoforms are critical to estradiol 17beta-D-glucuronide-induced cholestasis in the rat. Hepatology, 2008, 48, 1885-1895.
41. Roma, M.G.; Crocenzi, F.A.; Mottino, A.D. Dynamic localization of hepatocellular transporters in health and disease. World J. Gastroenterol., 2008, 14, 6786-6801.
42. Stieger, B.; Fattinger, K.; Madon, J.; Kullak-Ublick, G.A.; Meier, P.J. Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Gastroenterology, 2000, 118, 422-430.
43. Zollner, G.; Fickert, P.; Zenz, R.; Fuchsbichler, A.; Stumptner, C.; Kenner, L.; Ferenci, P.; Stauber, R.E.; Krejs, G.J.; Denk, H.; Zatloukal, K.; Trauner, M. Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases. Hepatology, 2001, 33, 633-646.
44. Elferink, M.G.; Olinga, P.; Draaisma, A.L.; Merema, M.T.; Faber, K.N.; Slooff, M.J.; Meijer, D.K.; Groothuis, G.M. LPS-induced downregulation of MRP2 and BSEP in human liver is due to a posttranscriptional process. Am. J. Physiol. Gastrointest. Liver Physiol., 2004, 287, G1008-G1016.
45. Vos, T.A.; Hooiveld, G.J.; Koning, H.; Childs, S.; Meijer, D.K.; Moshage, H.; Jansen, P.L.; Müller, M. Up-regulation of the multidrug resistance genes, Mrp1 and Mdr1b, and down-regulation of the organic anion transporter, Mrp2, and the bile salt transporter, Spgp, in endotoxemic rat liver. Hepatology, 1998, 28, 1637-1644.
46. Schuster, D.; Laggner, C.; Langer, T. Why drugs fail--a study on side effects in new chemical entities. Curr. Pharm. Des., 2005, 11, 3545-3559.
47. Smith, D.A.; Schmid, E.F. Drug withdrawals and the lessons within. Curr. Opin. Drug Discov. Devel., 2006, 9, 38-46.
48. Mita, S.; Suzuki, H.; Akita, H.; Hayashi, H.; Onuki, R.; Hofmann, A.F.; Sugiyama, Y. Inhibition of bile acid transport across Na+/taurocholate cotransporting polypeptide (SLC10A1) and bile salt export pump (ABCB 11)-coexpressing LLC-PK1 cells by cholestasis-inducing drugs. Drug Metab. Dispos., 2006, 34,1575-1581.
49. Roman, I.D.; Fernandez-Moreno, M.D.; Fueyo, J.A.; Roma, M.G.; Coleman, R. Cyclosporin A induced internalization of the bile salt export pump in isolated rat hepatocyte couplets. Toxicol. Sci., 2003, 71, 276-281.
50. Kipp, H.; Arias, I.M. Newly synthesized canalicular ABC transporters are directly targeted from the Golgi to the hepatocyte apical domain in rat liver. J. Biol. Chem., 2000, 275, 15917-15925.
51. Kipp, H.; Pichetshote, N.; Arias, I.M. Transporters on demand: intrahepatic pools of canalicular ATP binding cassette transporters in rat liver. J Biol Chem., 2001, 276, 7218-7224.
52. Wakabayashi, Y.; Lippincott-Schwartz, J.; Arias, I.M. Intracellular trafficking of bile salt export pump (ABCB11) in polarized hepatic cells: constitutive cycling between the canalicular membrane and rab11-positive endosomes. Mol. Biol. Cell, 2004, 15, 3485-3496.
53. Wang, L.; Dong, H.; Soroka, C.J.; Wei, N.; Boyer, J.L.; Hochstrasser, M. Degradation of the bile salt export pump at endoplasmic reticulum in progressive familial intrahepatic cholestasis type II. Hepatology, 2008, 48, 1558-1569.
54. Ruddock, L.W.; Molinari, M. N-glycan processing in ER quality control. J. Cell Sci., 2006, 119, 4373-4380.
55. Mochizuki, K.; Kagawa, T.; Numari, A.; Harris, M.J.; Itoh, J.; Watanabe, N.; Mine, T.; Arias, I.M. Two N-linked glycans are required to maintain the transport activity of the bile salt export pump (ABCB11) in MDCK II cells. Am. J. Physiol. Gastrointest. Liver Physiol., 2007; 292, G818-G828.
56. Kubitz, R.; Sutfels, G.; Kuhlkamp, T.; Kolling, R.; Haussinger, D. Trafficking of the bile salt export pump from the Golgi to the canalicular membrane is regulated by the p38 MAP kinase. Gastroenterology, 2004, 126, 541-553.
57. Chan, W.; Calderon, G.; Swift, A.L.; Moseley, J.; Li, S.; Hosoya, H.; Arias, I.M.; Ortiz, D.F. Myosin II regulatory light chain is required for trafficking of bile salt export protein to the apical membrane in Madin-Darby canine kidney cells. J. Biol. Chem., 2005, 280, 23741-23747.
58. Ortiz, D.F.; Moseley, J.; Calderon, G.; Swift, A.L.; Li, S.; Arias, I.M. Identification of HAX-1 as a protein that binds bile salt export protein and regulates its abundance in the apical membrane of Madin-Darby canine kidney cells. J. Biol. Chem., 2004, 279, 32761-32770.
59. McMahon, H.T.; Boucrot, E. Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nat. Rev. Mol. Cell. Biol., 2011, 12, 517-533.
60. Hayashi, H.; Inamura, K.; Aida, K.; Naoi, S.; Horikawa, R.; Nagasaka, H.; Takatani, T.; Fukushima, T.; Hattori, A.; Yabuki, T.; Horii, I.; Sugiyama, Y. et al. AP2 mediates BSEP internalization and modulates its hepatocanalicular expression and transport function. Hepatology, 2012, 55, 1889-1900.
61. Lam, P.; Xu, S.; Soroka, C.J.; Boyer, J.L. A C-terminal tyrosine-based motif in the bile salt export pump directs clathrin-dependent endocytosis. Hepatology, 2012, 55, 1901-1911.
62. Hayashi, H.; Sugiyama, Y. Short-chain ubiquitination is associated with the degradation rate of a cell-surface-resident bile salt export pump (BSEP/ABCB11). Mol. Pharmacol., 2009, 75, 143-150.
63. d'Azzo, A.; Bongiovanni, A.; Nastasi, T. E3 ubiquitin ligases as regulators of membrane protein trafficking and degradation. Traffic, 2005, 6, 429-441.
64. Raiborg, C.; Bache, K.G.; Gillooly, D.J.; Madshus, I.H.; Stang, E.; Stenmark, H. Hrs sorts ubiquitinated proteins into clathrin-coated microdomains of early endosomes. Nat. Cell. Biol., 2002, 4, 394-398.
65. Raiborg, C.; Stenmark, H. The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature, 2009, 458, 445-452.
66. Paumgartner, G.; Beuers, U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology, 2002, 36, 525-531.
67. Lapenna, D.; Ciofani, G.; Festi, D.; Neri, M.; Pierdomenico, S.D.; Giamberardino, M.A.; Cuccurullo, F. Antioxidant properties of ursodeoxycholic acid. Biochem. Pharmacol., 2002, 64, 1661-1667.
68. Mitsuyoshi, H.; Nakashima, T.; Sumida, Y.; Yoh, T.; Nakajima, Y.; Ishikawa, H.; Inaba, K.; Sakamoto, Y.; Okanoue, T.; Kashima, K. Ursodeoxycholic acid protects hepatocytes against oxidative injury via induction of antioxidants. Biochem. Biophys. Res. Commun., 1999, 263, 537-542.
69. Perez, M.J.; Briz, O. Bile-acid-induced cell injury and protection. World J. Gastroenterol., 2009, 15, 1677-1689.
70. Rodrigues, C.M.; Fan, G.; Wong, P.Y.; Kren, B.T.; Steer, C.J. Ursodeoxycholic acid may inhibit deoxycholic acid-induced apoptosis by modulating mitochondrial transmembrane potential and reactive oxygen species production. Mol. Med., 1998, 4, 165-178.
71. Kurz, A.K.; Graf, D.; Schmitt, M.; Vom Dahl, S.; Haussinger, D. Tauroursodesoxycholate-induced choleresis involves p38(MAPK) activation and translocation of the bile salt export pump in rats. Gastroenterology, 2001, 121, 407-419.
72. Dombrowski, F.; Stieger, B.; Beuers, U. Tauroursodeoxycholic acid inserts the bile salt export pump into canalicular membranes of cholestatic rat liver. Lab Invest., 2006, 86, 166-174.
73. Wimmer, R.; Hohenester, S.; Pusl, T.; Denk, G.U.; Rust, C.; Beuers, U. Tauroursodeoxycholic acid exerts anticholestatic effects by a cooperative cPKC alpha-/PKA-dependent mechanism in rat liver. Gut, 2008, 57,1448-1454.
74. Kajimura, K.; Takagi, Y.; Ueba, N.; Yamasaki, K.; Sakagami, Y.; Yokoyama, H.; Yoneda, K. Protective effect of Astragali Radix by intraperitoneal injection against Japanese encephalitis virus infection in mice. Biol. Pharm. Bull., 1996, 19, 855-859.
75. Burrows, J.A.; Willis, L.K.; Perlmutter, D.H. Chemical chaperones mediate increased secretion of mutant alpha 1-antitrypsin (alpha 1-AT) Z: A potential pharmacological strategy for prevention of liver injury and emphysema in alpha 1-AT deficiency. Proc. Natl. Acad. Sci. USA, 2000, 97, 1796-1801.
76. Rubenstein, R.C.; Egan, M.E.; Zeitlin, P.L. In vitro pharmacologic restoration of CFTR-mediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing delta F508-CFTR. J. Clin. Invest., 1997, 100, 2457-2465.
77. Rubenstein, R.C.; Zeitlin, P.L. A pilot clinical trial of oral sodium 4-phenylbutyrate (Buphenyl) in deltaF508-homozygous cystic fibrosis patients: partial restoration of nasal epithelial CFTR function. Am. J. Respir. Crit. Care Med., 1998, 157, 484-490.
78. Kojima, H.; Nies, A.T.; Konig, J.; Hagmann, W.; Spring, H.; Uemura, M.; Fukui, H.; Keppler, D.; et al. Changes in the expression and localization of hepatocellular transporters and radixin in primary biliary cirrhosis. J. Hepatol., 2003, 39, 693-702.
79. Shoda, J.; Kano, M.; Oda, K.; Kamiya, J.; Nimura, Y.; Suzuki, H.; Sugiyama, Y.; Miyazaki, H.; Todoroki, T.; Stengelin, S.; Kramer, W.; Matsuzaki, Y.; Tanaka, N. et al. The expression levels of plasma membrane transporters in the cholestatic liver of patients undergoing biliary drainage and their association with the impairment of biliary secretory function. Am. J. Gastroenterol., 2001, 96, 3368-3378.
80. Al-Anati, L.; Essid, E.; Reinehr, R.; Petzinger, E. Silibinin protects OTA-mediated TNF-alpha release from perfused rat livers and isolated rat Kupffer cells. Mol. Nutr. Food Res., 2009, 53, 460-466.
81. Crocenzi, F.A.; Basiglio, C.L.; Perez, L.M.; Portesio, M.S.; Pozzi, E.J.; Roma, M.G. Silibinin prevents cholestasis-associated retrieval of the bile salt export pump, Bsep, in isolated rat hepatocyte couplets: possible involvement of cAMP. Biochem. Pharmacol., 2005, 69, 1113-1120.