The bile salt export pump

Pflugers Archiv European Journal of Physiology

Volumn 453, Issue 5, 2007, Pages 611-620

  Stieger, Bruno ^a   Meier, Yvonne ^a   Meier, Peter J ^b  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^b UNIVERSITY OF BASEL   (Switzerland)

Author keywords

ATP binding cassette transporter; Bile acid transport; Bile formation; Mutation; Polymorphism

Indexed keywords

ABC TRANSPORTER; ABC TRANSPORTER B11; BILE SALT; UNCLASSIFIED DRUG;

BILE FLOW; DISEASE PREDISPOSITION; DOWN REGULATION; ENZYME SPECIFICITY; GENE EXPRESSION; GENE FUNCTION; GENE MUTATION; GENETIC VARIABILITY; HUMAN; LIVER DISEASE; NONHUMAN; ONTOGENY; PRIORITY JOURNAL; REVIEW; TISSUE DISTRIBUTION; TRANSCRIPTION REGULATION;

AMINO ACID SEQUENCE; ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; BILE ACIDS AND SALTS; BILE CANALICULI; CHOLESTASIS, INTRAHEPATIC; GENE EXPRESSION REGULATION; HUMANS; LIVER; MICE; MOLECULAR SEQUENCE DATA; RATS; RNA-BINDING PROTEINS; TRANSCRIPTION, GENETIC;

EID: 33846658726     PISSN: 00316768     EISSN: 14322013     Source Type: Journal    
DOI: 10.1007/s00424-006-0152-8     Document Type: Review

References (106)

1. Akita H, Suzuki H, Ito K, Kinoshita S, Sato N, Takikawa H, Sugiyama Y (2001) Characterization of bile acid transport mediated by multidrug resistance associated protein 2 and bile salt export pump. Biochim Biophys Acta 1511:7-16
2. Albrecht C, Elliott JI, Sardini A, Litman T, Stieger B, Meier PJ, Higgins CF (2002) Functional analysis of candidate ABC transporter proteins for sitosterol transport. Biochim Biophys Acta 1567:133-142
3. Ananthanarayanan M, Balasubramanian N, Makishima M, Mangelsdorf DJ, Suchy FJ (2001) Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile acid receptor. J Biol Chem 276:28857-28865
4. Anwer MS (2004) Cellular regulation of hepatic bile acid transport in health and cholestasis. Hepatology 39:581-590
5. Beuers U (2006) Drug Insight: mechanisms and sites of action of ursodeoxycholic acid in cholestasis. Nat Clin Pract Gastroenterol Hepatol 3:318-328
6. Bohme M, Muller M, Leier I, Jedlitschky G, Keppler D (1994) Cholestasis caused by inhibition of the adenosine triphosphate-dependent bile salt transport in rat liver. Gastroenterology 107:255-265
7. Bolder U, Jeschke MG, Landmann L, Wolf F, de Sousa C, Schlitt HJ, Przkora R (2006) Heat stress enhances recovery of hepatocyte bile acid and organic anion transporters in endotoxemic rats by multiple mechanisms. Cell Stress Chaperones 11:89-100
8. Boyer JL, Soroka CJ (1995) Vesicle targeting to the apical domain regulates bile excretory function in isolated rat hepatocyte couplets. Gastroenterology 109:1600-1611
9. Byrne JA, Strautnieks SS, Mieli-Vergani G, Higgins CF, Linton KJ, Thompson RJ (2002) The human bile salt export pump: characterization of substrate specificity and identification of inhibitors. Gastroenterology 123:1649-1658
10. Cai SY, Wang L, Ballatori N, Boyer JL (2001) Bile salt export pump is highly conserved during vertebrate evolution and its expression is inhibited by PFIC type II mutations. Am J Physiol Gastrointest Liver Physiol 281:G316-G322
11. Cariou B, van Harmelen K, Duran-Sandoval D, van Dijk TH, Grefhorst A, Abdelkarim M, Caron S, Torpier G, Fruchart JC, Gonzalez FJ, Kuipers F, Staels B (2006) The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice. J Biol Chem 281:11039-11049
12. Chan W, Calderon G, Swift AL, Moseley J, Li S, Hosoya H, Arias IM, Ortiz DF (2005) 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 280:23741-23747
13. Chen HL, Liu YJ, Feng CH, Wu CY, Shyu MK, Yuan RH, Chang MH (2005) Developmental expression of canalicular transporter genes in human liver. J Hepatol 43:472-477
14. Childs S, Yeh RL, Georges E, Ling V (1995) Identification of a sister gene to P-glycoprotein. Cancer Res 55:2029-2034
15. Childs S, Yeh RL, Hui D, Ling V (1998) Taxol resistance mediated by transfection of the liver-specific sister gene of P-glycoprotein. Cancer Res 58:4160-4167
16. Claudel T, Staels B, Kuipers F (2005) The Farnesoid X receptor: a molecular link between bile acid and lipid and glucose metabolism. Arterioscler Thromb Vasc Biol 25:2020-2030
17. Crocenzi FA, Basiglio CL, Perez LM, Portesio MS, Pozzi EJ, Roma MG (2005) Silibinin prevents cholestasis-associated retrieval of the bile salt export pump, Bsep, in isolated rat hepatocyte couplets: possible involvement of cAMP. Biochem Pharmacol 69:1113-1120
18. Crocenzi FA, Mottino AD, Cao J, Veggi LM, Pozzi EJ, Vore M, Coleman R, Roma MG (2003) Estradiol-17beta-D-glucuronide induces endocytic internalization of Bsep in rats. Am J Physiol Gastrointest Liver Physiol 285:G449-G459
19. Crocenzi FA, Mottino AD, Sanchez Pozzi EJ, Pellegrino JM, Rodriguez Garay EA, Milkiewicz P, Vore M, Coleman R, Roma MG (2003) Impaired localisation and transport function of canalicular Bsep in taurolithocholate induced cholestasis in the rat. Gut 52:1170-1177
20. Dean M, Rzhetsky A, Allikmets R (2001) The human ATP-binding cassette (ABC) transporter superfamily. Genome Res 11:1156-1166
21. Dombrowski F, Stieger B, Beuers U (2006) Tauroursodeoxycholic acid inserts the bile salt export pump into canalicular membranes of cholestatic rat liver. Lab Invest 86:166-174
22. Elferink MG, Olinga P, Draaisma AL, Merema MT, Faber KN, Slooff MJ, Meijer DK, Groothuis GM (2004) LPS-induced downregulation of MRP2 and BSEP in human liver is due to a posttranscriptional process. Am J Physiol Gastrointest Liver Physiol 287:G1008-G1016
23. Eloranta JJ, Kullak-Ublick GA (2005) Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism. Arch Biochem Biophys 433:397-412
24. Eloranta ML, Hakli T, Hiltunen M, Helisalmi S, Punnonen K, Heinonen S (2003) Association of single nucleotide polymorphisms of the bile salt export pump gene with intrahepatic cholestasis of pregnancy. Scand J Gastroenterol 38:648-652
25. Fattinger K, Funk C, Pantze M, Weber C, Reichen J, Stieger B, Meier PJ (2001) The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions. Clin Pharmacol Ther 69:223-231
26. Figge A, Lammert F, Paigen B, Henkel A, Matern S, Korstanje R, Shneider BL, Chen F, Stoltenberg E, Spatz K, Hoda F, Cohen DE, Green RM (2004) Hepatic overexpression of murine Abcb11 increases hepatobiliary lipid secretion and reduces hepatic steatosis. J Biol Chem 279:2790-2799
27. Fiorucci S, Clerici C, Antonelli E, Orlandi S, Goodwin B, Sadeghpour BM, Sabatino G, Russo G, Castellani D, Willson TM, Pruzanski M, Pellicciari R, Morelli A (2005) Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis. J Pharmacol Exp Ther 313:604-612
28. Fouassier L, Kinnman N, Lefevre G, Lasnier E, Rey C, Poupon R, Elferink RP, Housset C (2002) Contribution of mrp2 in alterations of canalicular bile formation by the endothelin antagonist bosentan. J Hepatol 37:184-191
29. Funk C, Ponelle C, Scheuermann G, Pantze M (2001) Cholestatic potential of troglitazone as a possible factor contributing to troglitazone-induced hepatotoxicity: in vivo and in vitro interaction at the canalicular bile salt export pump (Bsep) in the rat. Mol Pharmacol 59:627-635
30. Gao B, St Pierre MV, Stieger B, Meier PJ (2004) Differential expression of bile salt and organic anion transporters in developing rat liver. J Hepatol 41:201-208
31. Gatmaitan ZC, Nies AT, Arias IM (1997) Regulation and translocation of ATP-dependent apical membrane proteins in rat liver. Am J Physiol Gastrointest Liver Physiol 272:G1041-G1049
32. Gerloff T, Geier A, Roots I, Meier PJ, Gartung C (2002) Functional analysis of the rat bile salt export pump gene promoter. Eur J Biochem 269:3495-3503
33. Gerloff T, Stieger B, Hagenbuch B, Madon J, Landmann L, Roth J, Hofmann AF, Meier PJ (1998) The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. J Biol Chem 273:10046-10050
34. Geuken E, Visser D, Kuipers F, Blokzijl H, Leuvenink HG, de Jong KP, Peeters PM, Jansen PL, Slooff MJ, Gouw AS, Porte RJ (2004) Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation. J Hepatol 41:1017-1025
35. Green RM, Hoda F, Ward KL (2000) Molecular cloning and characterization of the murine bile salt export pump. Gene 241:117-123
36. Hayakawa T, Bruck R, Ng OC, Boyer JL (1990) DBcAMP stimulates vesicle transport and HRP excretion in isolated perfused rat liver. Am J Physiol Gastrointest Liver Physiol 259: G727-G735
37. Hayashi H, Takada T, Suzuki H, Akita H, Sugiyama Y (2005) Two common PFIC2 mutations are associated with the impaired membrane trafficking of BSEP/ABCB11. Hepatology 41:916-924
38. Hayashi H, Takada T, Suzuki H, Onuki R, Hofmann AF, Sugiyama Y (2005) 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 1738:54-62
39. Higgins CF, Gottesman MM (1992) Is the multidrug transporter a flippase? Trends Biochem Sci 17:18-21
40. Hirano M, Maeda K, Hayashi H, Kusuhara H, Sugiyama Y (2005) Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin. J Pharmacol Exp Ther 314:876-882
41. Honjo Y, Sasaki S, Kobayashi Y, Misawa H, Nakamura H (2006) 1,25-Dihydroxyvitamin D3 and its receptor inhibit the chenodeoxycholic acid-dependent transactivation by farnesoid X receptor. J Endocrinol 188:635-643
42. Hortensteiner S, Vogt E, Hagenbuch B, Meier PJ, Amrhein N, Martinoia E (1993) Direct energization of bile acid transport into plant vacuoles. J Biol Chem 268:18446-18449
43. Houten SM, Watanabe M, Auwerx J (2006) Endocrine functions of bile acids. EMBO J 25:1419-1425
44. Huang W, Ma K, Zhang J, Qatanani M, Cuvillier J, Liu J, Dong B, Huang X, Moore DD (2006) Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration. Science 312:233-236
45. Jansen PLM, Strautnieks SS, Jacquemin E, Hadchouel M, Sokal EM, Hooiveld GJ, Koning JH, De Jager Krikken A, Kuipers F, Stellaard F, Bijleveld CM, Gouw A, Van Goor H, Thompson RJ, Muller M (1999) Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis. Gastroenterology 117:1370-1379
46. Keitel V, Burdelski M, Warskulat U, Kuhlkamp T, Keppler D, Haussinger D, Kubitz R (2005) Expression and localization of hepatobiliary transport proteins in progressive familial intrahepatic cholestasis. Hepatology 41:1160-1172
47. Kipp H, Arias IM (2002) Trafficking of canalicular ABC transporters in hepatocytes. Annu Rev Physiol 64:595-608
48. Kipp H, Pichetshote N, Arias IM (2001) Transporters on demand: intrahepatic pools of canalicular ATP binding cassette transporters in rat liver. J Biol Chem 276:7218-7224
49. Krahenbuhl S, Talos C, Fischer S, Reichen J (1994) Toxicity of bile acids on the electron transport chain of isolated rat liver mitochondria. Hepatology 19:471-479
50. Kullak-Ublick GA, Stieger B, Meier PJ (2004) Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology 126:322-342
51. Lam CW, Cheung KM, Tsui MS, Yan MS, Lee CY, Tong SF (2006) A patient with novel ABCB11 gene mutations with phenotypic transition between BRIC2 and PFIC2. J Hepatol 44:240-242
52. Lam P, Wang R, Ling V (2005) Bile acid transport in sister of P-glycoprotein (ABCB11) knockout mice. Biochemistry 44:12598-12605
53. Langmann T, Mauerer R, Zahn A, Moehle C, Probst M, Stremmel W, Schmitz G (2003) Real-time reverse transcription-PCR expression profiling of the complete human ATP-binding cassette transporter superfamily in various tissues. Clin Chem 49:230-238
54. Lecureur V, Sun D, Hargrove P, Schuetz EG, Kim RB, Lan LB, Schuetz JD (2000) Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein. Mol Pharmacol 57:24-35
55. Lee JM, Trauner M, Soroka CJ, Stieger B, Meier PJ, Boyer JL (2000) Expression of the bile salt export pump is maintained after chronic cholestasis in the rat. Gastroenterology 118:163-172
56. Ljubuncic P, Yousef I, Bomzon A (2004) Cholemic transgenic mice: a novel animal model to investigate the effects of bile acids. J Pharmacol Toxicol Methods 50:231-235
57. Luttringer O, Theil FP, Lave T, Wernli-Kuratli K, Guentert TW, de Saizieu A (2002) Influence of isolation procedure, extracellular matrix and dexamethasone on the regulation of membrane transporters gene expression in rat hepatocytes. Biochem Pharmacol 64:1637-1650
58. Ma K, Saha PK, Chan L, Moore DD (2006) Farnesoid X receptor is essential for normal glucose homeostasis. J Clin Invest 116:1102-1109
59. Marschall HU, Wagner M, Zollner G, Fickert P, Diczfalusy U, Gumhold J, Silbert D, Fuchsbichler A, Benthin L, Grundstrom R, Gustafsson U, Sahlin S, Einarsson C, Trauner M (2005) Complementary stimulation of hepatobiliary transport and detoxification systems by rifampicin and ursodeoxycholic acid in humans. Gastroenterology 129:476-485
60. Meier PJ (2002) Canalicular bile formation: beyond single transporter functions. J Hepatol 37:272-273
61. Meier PJ, Stieger B (2002) Bile salt transporters. Annu Rev Physiol 64:635-661
62. Meier Y, Cavallaro M, Roos M, Pauli-Magnus C, Folkers G, Meier PJ, Fattinger K (2005) Incidence of drug-induced liver injury in medical inpatients. Eur J Clin Pharmacol 61:135-143
63. Meier Y, Pauli-Magnus C, Zanger UM, Klein K, Schaeffeler E, Nussler AK, Nussler N, Eichelbaum M, Meier PJ, Stieger B (2006) Interindividual variability of canalicular ATP-binding-cassette (ABC)-transporter expression in human liver. Hepatology 44:62-74
64. Meyers RL, Book LS, O'Gorman MA, Jackson WD, Black RE, Johnson DG, Matlak ME (2003) High-dose steroids, ursodeoxycholic acid, and chronic intravenous antibiotics improve bile flow after Kasai procedure in infants with biliary atresia. J Pediatr Surg 38:406-411
65. Misra S, Ujhazy P, Varticovski L, Arias IM (1999) Phosphoinositide 3-kinase lipid products regulate ATP-dependent transport by sister of P-glycoprotein and multidrug resistance associated protein 2 in bile canalicular membrane vesicles. Proc Natl Acad Sci USA 96:5814-5819
66. Misra S, Varticovski L, Arias IM (2003) Mechanisms by which cAMP increases bile acid secretion in rat liver and canalicular membrane vesicles. Am J Physiol Gastrointest Liver Physiol 285:G316-G324
67. Moseley RH (1997) Sepsis-associated cholestasis.Gastroenterology 112:302-306
68. Muhlfeld A, Kubitz R, Dransfeld O, Haussinger D, Wettstein M (2003) Taurine supplementation induces multidrug resistance protein 2 and bile salt export pump expression in rats and prevents endotoxin-induced cholestasis. Arch Biochem Biophys 413:32-40
69. Noe J, Hagenbuch B, Meier PJ, St-Pierre MV (2001) Characterization of the mouse bile salt export pump overexpressed in the baculovirus system. Hepatology 33:1223-1231
70. Noe J, Kullak-Ublick GA, Jochum W, Stieger B, Kerb R, Haberl M, Mullhaupt B, Meier PJ, Pauli-Magnus C (2005) Impaired expression and function of the bile salt export pump due to three novel ABCB11 mutations in intrahepatic cholestasis. J Hepatol 43:536-543
71. Noe J, Meier PJ, St Pierre MV (2001) Functional characterization of the phosphorylation of the bile salt export pump by protein kinase C. Hepatology 34:255A
72. Noe J, Stieger B, Meier PJ (2002) Functional expression of the canalicular bile salt export pump of human liver. Gastroenterology 123:1659-1666
73. Ortiz DF, Moseley J, Calderon G, Swift AL, Li S, Arias IM (2004) 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 279:32761-32770
74. Ortiz DF, St Pierre MV, Abdulmessih A, Arias IM (1997) Ayeast ATP-binding cassette-type protein mediating ATP-dependent bile acid transport. J Biol Chem 272:15358-15365
75. Oude Elferink RP, Paulusma CC, Groen AK (2006) Hepatocanalicular transport defects: pathophysiologic mechanisms of rare diseases. Gastroenterology 130:908-925
76. Pauli-Magnus C, Kerb R, Fattinger K, Lang T, Anwald B, Kullak-Ublick GA, Beuers U, Meier PJ (2004) BSEP and MDR3 haplotype structure in healthy Caucasians, primary biliary cirrhosis and primary sclerosing cholangitis. Hepatology 39:779-791
77. Pauli-Magnus C, Meier PJ (2005) Hepatocellular transporters and cholestasis. J Clin Gastroenterol 39:S103-S110
78. Pauli-Magnus C, Stieger B, Meier Y, Kullak Ublick GA, Meier PJ (2005) Enterohepatic transport of bile salts and genetics of cholestasis. J Hepatol 43:342-357
79. Paumgartner G, Beuers U (2004) Mechanisms of action and therapeutic efficacy of ursodeoxycholic acid in cholestatic liver disease. Clin Liver Dis 8:67-81
80. Perwaiz S, Forrest D, Mignault D, Tuchweber B, Phillip MJ, Wang R, Ling V, Yousef IM (2003) Appearance of atypical 3 alpha,6 beta,7 beta,12 alpha-tetrahydroxy-5 beta-cholan-24-oic acid in spgp knockout mice. J Lipid Res 44:494-502
81. Plass JR, Mol O, Heegsma J, Geuken M, de Bruin J, Elling G, Muller M, Faber KN, Jansen PL (2004) A progressive familial intrahepatic cholestasis type 2 mutation causes an unstable, temperature-sensitive bile salt export pump. J Hepatol 40:24-30
82. Rippin SJ, Hagenbuch B, Meier PJ, Stieger B (2001) Cholestatic expression pattern of sinusoidal and canalicular organic anion transport systems in primary cultured rat hepatocytes. Hepatology 33:776-782
83. Schliess F, Kurz AK, vom Dahl S, Haussinger D (1997) Mitogen-activated protein kinases mediate the stimulation of bile acid secretion by tauroursodeoxycholate in rat liver. Gastroenterology 113:1306-1314
84. 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 (2001) 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 96:3368-3378
85. Sinal CJ, Tohkin M, Miyata M, Ward JM, Lambert G, Gonzalez FJ (2000) Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 102:731-744
86. Stieger B, Fattinger K, Madon J, Kullak Ublick GA, Meier PJ (2000) Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Gastroenterology 118:422-430
87. Stieger B, Meier PJ (1998) Bile acid and xenobiotic transporters in liver. Curr Opin Cell Biol 10:462-467
88. Strautnieks SS, Bull LN, Knisely AS, Kocoshis SA, Dahl N, Arnell H, Sokal E, Dahan K, Childs S, Ling V, Tanner MS, Kagalwalla AF, Nemeth A, Pawlowska J, Baker A, Mieli-Vergani G, Freimer NB, Gardiner RM, Thompson RJ (1998) A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat Genet 20:233-238
89. Tomer G, Ananthanarayanan M, Weymann A, Balasubramanian N, Suchy FJ (2003) Differential developmental regulation of rat liver canalicular membrane transporters bsep and mrp2. Pediatr Res 53:288-294
90. Torok M, Gutmann H, Fricker G, Drewe J (1999) Sister of P-glycoprotein expression in different tissues. Biochem Pharmacol 57:833-835
91. Trauner M, Boyer JL (2003) Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev 83:633-671
92. Turncliff RZ, Tian X, Brouwer KL (2006) Effect of culture conditions on the expression and function of Bsep, Mrp2, and Mdr1a/b in sandwich-cultured rat hepatocytes. Biochem Pharmacol 71:1520-1529
93. Vallejo M, Briz O, Serrano MA, Monte MJ, Marin JJ (2006) Potential role of trans-inhibition of the bile salt export pump by progesterone metabolites in the etiopathogenesis of intrahepatic cholestasis of pregnancy. J Hepatol 44:1150-1157
94. Vos TA, Hooiveld GJ, Koning H, Childs S, Meijer DK, Moshage H, Jansen PL, Muller M (1998) 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 28:1637-1644
95. Wakabayashi Y, Lippincott-Schwartz J, Arias IM (2004) 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 15:3485-3496
96. Wang L, Boyer JL (2004) The maintenance and generation of membrane polarity in hepatocytes. Hepatology 39:892-899
97. Wang L, Soroka CJ, Boyer JL (2002) The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II. J Clin Invest 110:965-972
98. Wang R, Lam P, Liu L, Forrest D, Yousef IM, Mignault D, Phillips MJ, Ling V (2003) Severe cholestasis induced by cholic acid feeding in knockout mice of sister of P-glycoprotein. Hepatology 38:1489-1499
99. Wang R, Salem M, Yousef IM, Tuchweber B, Lam P, Childs SJ, Helgason CD, Ackerley C, Phillips MJ, Ling V (2001) Targeted inactivation of sister of P-glycoprotein gene (spgp) in mice results in nonprogressive but persistent intrahepatic cholestasis. Proc Natl Acad Sci USA 98:2011-2016
100. Warskulat U, Kubitz R, Wettstein M, Stieger B, Meier PJ, Haussinger D (1999) Regulation of bile salt export pump mRNA levels by dexamethasone and osmolarity in cultured rat hepatocytes. Biol Chem 380:1273-1279
101. Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, Messaddeq N, Harney JW, Ezaki O, Kodama T, Schoonjans K, Bianco AC, Auwerx J (2006) Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 439:484-489
102. Wolters H, Elzinga BM, Baller JF, Boverhof R, Schwarz M, Stieger B, Verkade HJ, Kuipers F (2002) Effects of bile salt flux variations on the expression of hepatic bile salt transporters in vivo in mice. J Hepatol 37:556-563
103. Zinchuk V, Zinchuk O, Okada T (2005) Experimental LPS-induced cholestasis alters subcellular distribution and affects colocalization of Mrp2 and Bsep proteins: a quantitative colocalization study. Microsc Res Tech 67:65-70
104. Zinchuk VS, Okada T, Akimaru K, Seguchi H (2002) Asynchronous expression and colocalization of Bsep and Mrp2 during development of rat liver. Am J Physiol Gastrointest Liver Physiol 282:G540-G548
105. Zollner G, Fickert P, Silbert D, Fuchsbichler A, Marschall HU, Zatloukal K, Denk H, Trauner M (2003) Adaptive changes in hepatobiliary transporter expression in primary biliary cirrhosis. J Hepatol 38:717-727
106. Zollner G, Fickert P, Zenz R, Fuchsbichler A, Stumptner C, Kenner L, Ferenci P, Stauber RE, Krejs GJ, Denk H, Zatloukal K, Trauner M (2001) Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases. Hepatology 33:633-646