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Gene Review

Abcb11  -  ATP-binding cassette, subfamily B...

Rattus norvegicus

Synonyms: ATP-binding cassette sub-family B member 11, Bile salt export pump, Bsep, Sister of P-glycoprotein, Spgp
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Disease relevance of Abcb11

  • CONCLUSIONS: p38(MAPK) regulates BSEP trafficking from the Golgi to the canalicular membrane, and the Golgi may serve as a BSEP pool in certain forms of cholestasis or when p38(MAPK) activity is inhibited [1].
  • Troglitazone-induced intrahepatic cholestasis by an interference with the hepatobiliary export of bile acids in male and female rats. Correlation with the gender difference in troglitazone sulfate formation and the inhibition of the canalicular bile salt export pump (Bsep) by troglitazone and troglitazone sulfate [2].

High impact information on Abcb11

  • In isolated rat hepatocytes with intact bile secretion, no colocalization of rat isoforms of the bile salt export pump (Bsep) and Golgi was found, but colocalization occurred after inhibition of p38(MAPK) and PKC, suggesting that Bsep trafficking to the canalicular membrane depends on the basal activity of these kinases in polarized cells [1].
  • Also, tauroursodeoxycholate (TUDC), which activates p38(MAP) kinase (p38(MAPK), increased BSEP-positive pseudocanaliculi by more than 50% in rat sodium taurocholate cotransporting peptide (Ntcp)-transfected but not in untransfected HepG2 cells [1].
  • Cycloheximide, an inhibitor of protein translation, induced a microtubule- and p38(MAP) kinase-dependent decrease of Golgi-associated BSEP, accompanied by a more than 2-fold increase in BSEP-positive pseudocanaliculi [1].
  • Protein levels of the canalicular bile salt export pump (Bsep) were unchanged in diabetic rats, but basal biliary bile salt output and the SRm of taurocholate were increased by 260% and 130%, respectively, compared with controls [3].
  • Protein expression, messenger RNA levels, and tissue distribution of the bile acid transporters sodium taurocholate cotransporting protein (ntcp) and bile salt export pump (bsep) were also analyzed [4].

Chemical compound and disease context of Abcb11

  • CONCLUSIONS: These results provide a molecular basis for previous in vivo observations and identify Bsep as an important target for induction of drug- and estrogen-induced cholestasis in mammalian liver [5].
  • The data show that oral supplementation of taurine induces Mrp2 and Bsep expression and may prevent LPS-induced cholestasis [6].
  • Impaired localisation and transport function of canalicular Bsep in taurolithocholate induced cholestasis in the rat [7].

Biological context of Abcb11

  • The maximal secretory rate (nmol/min/g liver) for TC in the single pass isolated perfused liver was also increased by 10%, 31%, and 24% at 2, 14, and 21 days postpartum and correlated with increased expression of Ntcp and Bsep mRNA and protein [8].
  • Furthermore, Bsep and Mrp2 protein levels were maintained at about 50%, while the Mrp2 mRNA showed a transient up-regulation to 154% at 24 and 48 hours [9].
  • In contrast, the maximum secretory rate of tauroursodeoxycholate as well as expression of Bsep protein detected by Western blotting were not affected [10].
  • These results show that 1) expression (of mRNA and protein) of canalicular transporters is developmentally regulated by both transcriptional and posttranscriptional mechanisms and 2) Mrp2 and Bsep gene expression (mRNA) are differentially regulated [11].
  • 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 [12].

Anatomical context of Abcb11


Associations of Abcb11 with chemical compounds

  • Fusidate inhibited the ATP-dependent transport of the Mrp2 substrates 17beta-glucuronosyl estradiol and leukotriene C4, and the transport of cholyltaurine by Bsep with Ki values of 2.2+/-0.3, 7.6+/-1.3, and 5.5+/-0.8 microM, respectively [17].
  • Estradiol-17beta-d-glucuronide (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. cAMP stimulates the apically directed vesicular trafficking of transporters, partially preventing these alterations [18].
  • Sil (2.5microM) elevated by 40+/-3% intracellular cAMP, and mimicked the ability of dibutyryl-cAMP (10microM) to prevent internalisation of Bsep and the TLC (2.5microM)- and E(2)17G (50microM)-induced impairment in the capacity of IRHC to accumulate CLF apically [18].
  • We aimed to assess the ability of silibinin (Sil), the silymarin active component, to prevent the retrieval of Bsep induced by TLC and E(2)17G, and the associated alteration in its transport function [18].
  • Dexamethasone, hydrocortisone and phenobarbital had no effect on Bsep promoter activity [12].

Other interactions of Abcb11


Analytical, diagnostic and therapeutic context of Abcb11


  1. Trafficking of the bile salt export pump from the Golgi to the canalicular membrane is regulated by the p38 MAP kinase. Kubitz, R., Sütfels, G., Kühlkamp, T., Kölling, R., Häussinger, D. Gastroenterology (2004) [Pubmed]
  2. Troglitazone-induced intrahepatic cholestasis by an interference with the hepatobiliary export of bile acids in male and female rats. Correlation with the gender difference in troglitazone sulfate formation and the inhibition of the canalicular bile salt export pump (Bsep) by troglitazone and troglitazone sulfate. Funk, C., Pantze, M., Jehle, L., Ponelle, C., Scheuermann, G., Lazendic, M., Gasser, R. Toxicology (2001) [Pubmed]
  3. Differential effects of streptozotocin-induced diabetes on expression of hepatic ABC-transporters in rats. van Waarde, W.M., Verkade, H.J., Wolters, H., Havinga, R., Baller, J., Bloks, V., Müller, M., Sauer, P.J., Kuipers, F. Gastroenterology (2002) [Pubmed]
  4. Heat stress prevents impairment of bile acid transport in endotoxemic rats by a posttranscriptional mechanism. Bolder, U., Schmidt, A., Landmann, L., Kidder, V., Tange, S., Jauch, K.W. Gastroenterology (2002) [Pubmed]
  5. Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Stieger, B., Fattinger, K., Madon, J., Kullak-Ublick, G.A., Meier, P.J. Gastroenterology (2000) [Pubmed]
  6. Taurine supplementation induces multidrug resistance protein 2 and bile salt export pump expression in rats and prevents endotoxin-induced cholestasis. Mühlfeld, A., Kubitz, R., Dransfeld, O., Häussinger, D., Wettstein, M. Arch. Biochem. Biophys. (2003) [Pubmed]
  7. Impaired localisation and transport function of canalicular Bsep in taurolithocholate induced cholestasis in the rat. Crocenzi, F.A., Mottino, A.D., Sánchez Pozzi, E.J., Pellegrino, J.M., Rodríguez Garay, E.A., Milkiewicz, P., Vore, M., Coleman, R., Roma, M.G. Gut (2003) [Pubmed]
  8. Differential regulation of hepatic bile salt and organic anion transporters in pregnant and postpartum rats and the role of prolactin. Cao, J., Huang, L., Liu, Y., Hoffman, T., Stieger, B., Meier, P.J., Vore, M. Hepatology (2001) [Pubmed]
  9. Cholestatic expression pattern of sinusoidal and canalicular organic anion transport systems in primary cultured rat hepatocytes. Rippin, S.J., Hagenbuch, B., Meier, P.J., Stieger, B. Hepatology (2001) [Pubmed]
  10. Mechanisms involved in spironolactone-induced choleresis in the rat. Role of multidrug resistance-associated protein 2. Ruiz, M.L., Villanueva, S.S., Luquita, M.G., Sánchez-Pozzi, E.J., Crocenzi, F.A., Pellegrino, J.M., Ochoa, J.E., Vore, M., Mottino, A.D., Catania, V.A. Biochem. Pharmacol. (2005) [Pubmed]
  11. Differential developmental regulation of rat liver canalicular membrane transporters Bsep and Mrp2. Tomer, G., Ananthanarayanan, M., Weymann, A., Balasubramanian, N., Suchy, F.J. Pediatr. Res. (2003) [Pubmed]
  12. Functional analysis of the rat bile salt export pump gene promoter. Gerloff, T., Geier, A., Roots, I., Meier, P.J., Gartung, C. Eur. J. Biochem. (2002) [Pubmed]
  13. Regulation of the dynamic localization of the rat Bsep gene-encoded bile salt export pump by anisoosmolarity. Schmitt, M., Kubitz, R., Lizun, S., Wettstein, M., Häussinger, D. Hepatology (2001) [Pubmed]
  14. 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. Funk, C., Ponelle, C., Scheuermann, G., Pantze, M. Mol. Pharmacol. (2001) [Pubmed]
  15. Different pathways of canalicular secretion of sulfated and non-sulfated fluorescent bile acids: a study in isolated hepatocyte couplets and TR- rats. Mills, C.O., Milkiewicz, P., Müller, M., Roma, M.G., Havinga, R., Coleman, R., Kuipers, F., Jansen, P.L., Elias, E. J. Hepatol. (1999) [Pubmed]
  16. Tauroursodeoxycholic acid inserts the bile salt export pump into canalicular membranes of cholestatic rat liver. Dombrowski, F., Stieger, B., Beuers, U. Lab. Invest. (2006) [Pubmed]
  17. Inhibition of transport across the hepatocyte canalicular membrane by the antibiotic fusidate. Bode, K.A., Donner, M.G., Leier, I., Keppler, D. Biochem. Pharmacol. (2002) [Pubmed]
  18. Silibinin prevents cholestasis-associated retrieval of the bile salt export pump, Bsep, in isolated rat hepatocyte couplets: possible involvement of cAMP. Crocenzi, F.A., Basiglio, C.L., Pérez, L.M., Portesio, M.S., Pozzi, E.J., Roma, M.G. Biochem. Pharmacol. (2005) [Pubmed]
  19. Estradiol-17beta-D-glucuronide induces endocytic internalization of Bsep in rats. Crocenzi, F.A., Mottino, A.D., Cao, J., Veggi, L.M., Pozzi, E.J., Vore, M., Coleman, R., Roma, M.G. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  20. Differential expression of basolateral and canalicular organic anion transporters during regeneration of rat liver. Gerloff, T., Geier, A., Stieger, B., Hagenbuch, B., Meier, P.J., Matern, S., Gartung, C. Gastroenterology (1999) [Pubmed]
  21. Heat stress enhances recovery of hepatocyte bile acid and organic anion transporters in endotoxemic rats by multiple mechanisms. Bolder, U., Jeschke, M.G., Landmann, L., Wolf, F., de Sousa, C., Schlitt, H.J., Przkora, R. Cell Stress Chaperones (2006) [Pubmed]
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