bile salt export pump

Summary

Gene Symbol: bile salt export pump
Description: ATP binding cassette subfamily B member 11
Alias: Bsep, Spgp, bile salt export pump, ATP-binding cassette sub-family B member 11, ATP-binding cassette, sub-family B (MDR/TAP), member 11, ATP-binding cassette, subfamily B (MDR/TAP), member 11, sister of P-glycoprotein
Species: rat
Products:     bile salt export pump

Top Publications

  1. Donner M, Topp S, Cebula P, Krienen A, Gehrmann T, Sommerfeld A, et al. HbG200-mediated preinduction of heme oxygenase-1 improves bile flow and ameliorates pericentral downregulation of Bsep and Mrp2 following experimental liver ischemia and reperfusion. Biol Chem. 2013;394:97-112 pubmed publisher
    ..05) and biliary taurocholate excretion from 45.9±13.81 ?mol/3 h to 1.87±0.46 ?mol/3 h (p<0.05). Mrp2, Bsep and Ntcp peak immunofluorescence in pericentral hepatocytes decreased to 79.0±2.6% (p<0.001), 80.6±8...
  2. Wang L, Soroka C, Boyer J. The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II. J Clin Invest. 2002;110:965-72 pubmed
    ..familial intrahepatic cholestasis (PFIC) that is associated with mutations in the ABCB11 gene encoding the bile salt export pump (BSEP). However it is not known how these mutations cause this disease...
  3. Crocenzi F, Mottino A, Cao J, Veggi L, Pozzi E, Vore M, et al. Estradiol-17beta-D-glucuronide induces endocytic internalization of Bsep in rats. Am J Physiol Gastrointest Liver Physiol. 2003;285:G449-59 pubmed
    ..Here we evaluated in the rat whether a similar phenomenon occurs with the bile salt export pump (Bsep) and the ability of DBcAMP to prevent it. E217G (15 micromol/kg i.v...
  4. 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;314:876-82 pubmed
    ..It is generally accepted that the bile salt export pump (BSEP/ABCB11) mainly transports bile acids and plays an indispensable role in their biliary excretion...
  5. Lam P, Pearson C, Soroka C, Xu S, Mennone A, Boyer J. 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:C1709-16 pubmed
    Human BSEP (ABCB11) mutations are the molecular basis for at least three clinical forms of liver disease, progressive familial intrahepatic cholestasis type 2 (PFIC2), benign recurrent intrahepatic cholestasis type 2 (BRIC2), and ..
  6. 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;75:143-50 pubmed publisher
    The reduced expression of the bile salt export pump (BSEP/ABCB11) at the canalicular membrane is associated with cholestasis-induced hepatotoxicity due to the accumulation of bile acids in hepatocytes...
  7. Gerloff T, Geier A, Roots I, Meier P, Gartung C. Functional analysis of the rat bile salt export pump gene promoter. Eur J Biochem. 2002;269:3495-503 pubmed
    The 5' flanking region of the bile salt export pump (Bsep) gene was systematically analysed to provide the basis for understanding the mechanisms which regulate Bsep transcription...
  8. Crocenzi F, Basiglio C, Pérez L, Portesio M, Pozzi E, Roma M. Silibinin prevents cholestasis-associated retrieval of the bile salt export pump, Bsep, in isolated rat hepatocyte couplets: possible involvement of cAMP. Biochem Pharmacol. 2005;69:1113-20 pubmed
    ..E(2)17G) and taurolithocholate (TLC) induce acute cholestasis-associated with retrieval of the bile salt export pump (Bsep), which parallels with alteration in transport activity...
  9. Yska M, Buis C, Monbaliu D, Schuurs T, Gouw A, Kahmann O, et al. The role of bile salt toxicity in the pathogenesis of bile duct injury after non-heart-beating porcine liver transplantation. Transplantation. 2008;85:1625-31 pubmed publisher
    ..The role of bile salt toxicity in the development of biliary strictures after NHB liver transplantation is unclear...

More Information

Publications37

  1. Kagawa T, Watanabe N, Mochizuki K, Numari A, Ikeno Y, Itoh J, et al. 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:G58-67 pubmed
    ..cholestasis (PFIC) 2 and benign recurrent intrahepatic cholestasis (BRIC) 2 are caused by mutations in the bile salt export pump (BSEP, ABCB11) gene; however, their prognosis differs...
  2. Zinchuk V, Zinchuk O, Akimaru K, Moriya F, Okada T. Ethanol consumption alters expression and colocalization of bile salt export pump and multidrug resistance protein 2 in the rat. Histochem Cell Biol. 2007;127:503-12 pubmed
    ..regimen, we investigated the effects of chronic ethanol consumption on the expression and localization of bile salt export pump (Bsep), a major canalicular exporter of bile salts, and multidrug resistance protein 2 (Mrp2), a ..
  3. Tomer G, Ananthanarayanan M, Weymann A, Balasubramanian N, Suchy F. Differential developmental regulation of rat liver canalicular membrane transporters Bsep and Mrp2. Pediatr Res. 2003;53:288-94 pubmed
    ..Recently two major transporters that contribute to bile formation, the bile salt export pump (Bsep) and multidrug resistance protein-2 (Mrp2), have been cloned...
  4. Hayashi H, Inamura K, Aida K, Naoi S, Horikawa R, Nagasaka H, et al. AP2 adaptor complex mediates bile salt export pump internalization and modulates its hepatocanalicular expression and transport function. Hepatology. 2012;55:1889-900 pubmed publisher
    The bile salt export pump (BSEP) mediates the biliary excretion of bile salts and its dysfunction induces intrahepatic cholestasis...
  5. Wu T, Zhang Q, Li J, Chen H, Wu J, Song H. Up-regulation of BSEP and MRP2 by Calculus Bovis administration in 17?-ethynylestradiol-induced cholestasis: Involvement of PI3K/Akt signaling pathway. J Ethnopharmacol. 2016;190:22-32 pubmed publisher
    ..The histopathology of the liver tissue was evaluated. Expression of bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2) were studied by western blot and ..
  6. Kruglov E, Gautam S, Guerra M, Nathanson M. Type 2 inositol 1,4,5-trisphosphate receptor modulates bile salt export pump activity in rat hepatocytes. Hepatology. 2011;54:1790-9 pubmed publisher
    Bile salt secretion is mediated primarily by the bile salt export pump (Bsep), a transporter on the canalicular membrane of the hepatocyte. However, little is known about the short-term regulation of Bsep activity...
  7. Ortiz D, Moseley J, Calderon G, Swift A, Li S, Arias I. 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;279:32761-70 pubmed
    ATP-binding cassette (ABC)-type proteins are essential for bile formation in vertebrate liver. BSEP, MDR1, MDR2, and MRP2 ABC transporters are targeted to the apical (canalicular) membrane of hepatocytes where they execute ATP-dependent ..
  8. Mochizuki K, Kagawa T, Numari A, Harris M, Itoh J, Watanabe N, et al. 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:G818-28 pubmed
    ..glycosylation in protein stability, intracellular trafficking, and bile acid transport activity of the bile salt export pump [Bsep (ATP-binding cassette B11)]...
  9. Klett E, Lu K, Kosters A, Vink E, Lee M, Altenburg M, et al. A mouse model of sitosterolemia: absence of Abcg8/sterolin-2 results in failure to secrete biliary cholesterol. BMC Med. 2004;2:5 pubmed
    ..No phenotypic difference has yet been described in humans with complete defects in either ABCG5 or ABCG8. These proteins, based upon the defects in humans, are responsible for regulating dietary sterol entry and biliary sterol secretion...
  10. Pérez L, Milkiewicz P, Elias E, Coleman R, Sanchez Pozzi E, Roma M. Oxidative stress induces internalization of the bile salt export pump, Bsep, and bile salt secretory failure in isolated rat hepatocyte couplets: a role for protein kinase C and prevention by protein kinase A. Toxicol Sci. 2006;91:150-8 pubmed
    ..01). tBOOH-induced bile salt secretory failure was accompanied by internalization of the canalicular bile salt export pump (Bsep), and disarrangement of cytoskeletal F-actin...
  11. Gerloff T, Stieger B, Hagenbuch B, Madon J, Landmann L, Roth J, et al. The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. J Biol Chem. 1998;273:10046-50 pubmed
    ..These results indicate that the sister of P-glycoprotein is the major canalicular bile salt export pump of mammalian liver.
  12. Cheng Y, Chen S, Freeden C, Chen W, Zhang Y, Abraham P, et al. Bile Salt Homeostasis in Normal and Bsep Gene Knockout Rats with Single and Repeated Doses of Troglitazone. J Pharmacol Exp Ther. 2017;362:385-394 pubmed publisher
    The interference of bile acid secretion through bile salt export pump (BSEP) inhibition is one of the mechanisms for troglitazone (TGZ)-induced hepatotoxicity...
  13. Ou Q, Qian X, Li D, Zhang Y, Pei X, Chen J, et al. Yinzhihuang attenuates ANIT-induced intrahepatic cholestasis in rats through upregulation of Mrp2 and Bsep expressions. Pediatr Res. 2016;79:589-95 pubmed publisher
    ..Serum biomarkers, liver histology, and the distribution of protein and mRNA expression of Mrp2 and Bsep were analyzed...
  14. Kubitz R, Sütfels G, Kühlkamp T, Kölling 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;126:541-53 pubmed
    ..Trafficking of the bile salt export pump (BSEP) to the canalicular membrane was investigated in HepG2 cells and rat hepatocytes.
  15. Kipp H, Arias I. Newly synthesized canalicular ABC transporters are directly targeted from the Golgi to the hepatocyte apical domain in rat liver. J Biol Chem. 2000;275:15917-25 pubmed
    ..membrane targeting of newly synthesized canalicular ABC (ATP-binding cassette) transporters MDR1, MDR2, and SPGP (sister of P-glycoprotein) with that of cCAM105...
  16. Vos T, Hooiveld G, Koning H, Childs S, Meijer D, Moshage H, et al. 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;28:1637-44 pubmed
    ..Both the mRNA and protein levels of the sister of P-glycoprotein (spgp), the recently cloned bile salt transporter, decreased...
  17. Strautnieks S, Bull L, Knisely A, Kocoshis S, Dahl N, Arnell H, et al. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat Genet. 1998;20:233-8 pubmed
    ..The product of the orthologous rat gene has been shown to be an effective bile acid transporter in vitro. These data provide evidence that SPGP is the human bile salt export pump (BSEP).
  18. Fouassier L, Beaussier M, Schiffer E, Rey C, Barbu V, Mergey M, et al. Hypoxia-induced changes in the expression of rat hepatobiliary transporter genes. Am J Physiol Gastrointest Liver Physiol. 2007;293:G25-35 pubmed
    ..reduction in the mRNA levels of Na(+)-taurocholate-cotransporting polypeptide (Ntcp), bile salt export protein (Bsep), and multidrug resistance-associated protein 2 (Mrp2) and an increase in those of Cftr were detected before bile ..
  19. Jemnitz K, Veres Z, Vereczkey L. Contribution of high basolateral bile salt efflux to the lack of hepatotoxicity in rat in response to drugs inducing cholestasis in human. Toxicol Sci. 2010;115:80-8 pubmed publisher
    Intrahepatic bile acid accumulation due to inhibition of the bile salt export pump (BSEP) has been proposed as a mechanism for drug-induced cholestasis...
  20. Cantore M, Reinehr R, Sommerfeld A, Becker M, Haussinger D. The Src family kinase Fyn mediates hyperosmolarity-induced Mrp2 and Bsep retrieval from canalicular membrane. J Biol Chem. 2011;286:45014-29 pubmed publisher
    ..D'urso, D., Keppler, D., and Häussinger, D. (1997) Gastroenterology 113, 1438-1442) and Bsep retrieval (Schmitt, M., Kubitz, R., Lizun, S., Wettstein, M., and Häussinger, D...
  21. Ito M, Yamanashi Y, Toyoda Y, Izumi Nakaseko H, Oda S, Sugiyama A, et al. Disruption of Stard10 gene alters the PPAR?-mediated bile acid homeostasis. Biochim Biophys Acta. 2013;1831:459-68 pubmed publisher
    ..These results indicate that STARD10 is involved in regulating bile acid metabolism through the modulation of PPAR?-mediated mechanism. ..
  22. Monte M, Fernandez Tagarro M, Macias R, Jimenez F, González San Martín F, Marin J. Changes in the expression of genes related to bile acid synthesis and transport by the rat liver during hepatocarcinogenesis. Clin Sci (Lond). 2005;109:199-207 pubmed
    ..A progressive loss of mRNA for transporters (more marked for Ntcp, Bsep and Mrp2 than for Oatp1/Oatp1a1, Oatp2/Oatp1a4 and Oatp4/Oatp1b2) was found...
  23. Kikuchi S, Hata M, Fukumoto K, Yamane Y, Matsui T, Tamura A, et al. Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes. Nat Genet. 2002;31:320-5 pubmed
    ..These findings indicate that radixin is required for secretion of conjugated bilirubin through its support of Mrp2 localization at BCMs...
  24. Kawase A, Yamada A, Gamou Y, Tahara C, Takeshita F, Murata K, et al. Increased effects of ginsenosides on the expression of cholesterol 7?-hydroxylase but not the bile salt export pump are involved in cholesterol metabolism. J Nat Med. 2013;67:545-53 pubmed publisher
    ..the mRNA expression of cholesterol metabolism-related proteins such as cytochrome P450 (CYP)7A1 and bile salt export pump (BSEP) in the liver in hypercholesterolemic rats and rat primary hepatocytes...
  25. Donner M, Schumacher S, Warskulat U, Heinemann J, Haussinger D. Obstructive cholestasis induces TNF-alpha- and IL-1 -mediated periportal downregulation of Bsep and zonal regulation of Ntcp, Oatp1a4, and Oatp1b2. Am J Physiol Gastrointest Liver Physiol. 2007;293:G1134-46 pubmed
    ..We studied whether obstructive cholestasis (bile duct ligation) and LPS treatment affect the zonal expression of Bsep (Abcb11), Mrp4 (Abcc4), Ntcp (Slc10a1), and Oatp isoforms (Slco1a1, Slco1a4, and slco1b2) in rat liver, as analyzed ..
  26. Diao L, Li N, Brayman T, Hotz K, Lai Y. Regulation of MRP2/ABCC2 and BSEP/ABCB11 expression in sandwich cultured human and rat hepatocytes exposed to inflammatory cytokines TNF-{alpha}, IL-6, and IL-1{beta}. J Biol Chem. 2010;285:31185-92 pubmed publisher
    In the present study MRP2/ABCC2 and BSEP/ABCB11 expression were investigated in sandwich cultured (SC) human and rat hepatocytes exposed to the proinflammatory cytokines...
  27. Shih D, Bussen M, Sehayek E, Ananthanarayanan M, Shneider B, Suchy F, et al. Hepatocyte nuclear factor-1alpha is an essential regulator of bile acid and plasma cholesterol metabolism. Nat Genet. 2001;27:375-82 pubmed
    ..Our studies demonstrate that Tcf1, in addition to being an important regulator of insulin secretion, is an essential transcriptional regulator of bile acid and HDL-cholesterol metabolism. ..
  28. Song X, Chen Y, Valanejad L, Kaimal R, Yan B, Stoner M, et al. Mechanistic insights into isoform-dependent and species-specific regulation of bile salt export pump by farnesoid X receptor. J Lipid Res. 2013;54:3030-44 pubmed publisher
    Expression of bile salt export pump (BSEP) is regulated by the bile acid/farnesoid X receptor (FXR) signaling pathway. Two FXR isoforms, FXR?1 and FXR?2, are predominantly expressed in human liver...