Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2014, Article ID 954781, 11 pages
http://dx.doi.org/10.1155/2014/954781
Review Article

Molecular Mechanisms for Biliary Phospholipid and Drug Efflux Mediated by ABCB4 and Bile Salts

Department of Pharmacy, Shiga University of Medical Science Hospital, Otsu, Shiga 520-2192, Japan

Received 23 May 2014; Accepted 14 June 2014; Published 15 July 2014

Academic Editor: Yoshinori Marunaka

Copyright © 2014 Shin-ya Morita and Tomohiro Terada. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. M. van der Bliek, P. M. Bliek, C. Schneider et al., “Sequence of mdr3 cDNA encoding a human P-glycoprotein,” Gene, vol. 71, no. 2, pp. 401–411, 1988. View at Google Scholar
  2. C. R. Lincke, J. J. M. Smit, T. van der Velde-Koerts, and P. Borst, “Structure of the human MDR3 gene and physical mapping of the human MDR locus,” Journal of Biological Chemistry, vol. 266, no. 8, pp. 5303–5310, 1991. View at Google Scholar · View at Scopus
  3. M. M. Gottesman, T. Fojo, and S. E. Bates, “Multidrug resistance in cancer: role of ATP-dependent transporters,” Nature Reviews Cancer, vol. 2, no. 1, pp. 48–58, 2002. View at Publisher · View at Google Scholar · View at Scopus
  4. R. P. J. Oude Elferink and C. C. Paulusma, “Function and pathophysiological importance of ABCB4 (MDR3 P-glycoprotein),” Pflugers Archiv European Journal of Physiology, vol. 453, no. 5, pp. 601–610, 2007. View at Publisher · View at Google Scholar · View at Scopus
  5. A. H. Schinkel, M. E. M. Roelofs, and P. Borst, “Characterization of the human MDR3 P-glycoprotein and its recognition by P-glycoprotein-specific monoclonal antibodies,” Cancer Research, vol. 51, no. 10, pp. 2628–2635, 1991. View at Google Scholar · View at Scopus
  6. R. L. Juliano and V. Ling, “A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants,” Biochimica et Biophysica Acta, vol. 455, no. 1, pp. 152–162, 1976. View at Publisher · View at Google Scholar · View at Scopus
  7. I. B. Roninson, J. E. Chin, K. Choi et al., “Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 83, no. 12, pp. 4538–4542, 1986. View at Publisher · View at Google Scholar · View at Scopus
  8. K. Ueda, M. M. Cornwell, M. M. Gottesman et al., “The mdrl gene, responsible for multidrug-resistance, codes for P-glycoprotein,” Biochemical and Biophysical Research Communications, vol. 141, no. 3, pp. 956–962, 1986. View at Publisher · View at Google Scholar · View at Scopus
  9. K. Ueda, C. Cardarelli, M. M. Gottesman, and T. Pastan, “Expression of a full-length cDNA for the human 'MDR1' gene confers resistance to colchicine, doxorubicin, and vinblastine,” Proceedings of the National Academy of Sciences of the United States of America, vol. 84, no. 9, pp. 3004–3008, 1987. View at Publisher · View at Google Scholar · View at Scopus
  10. A. M. van der Bliek, F. Baas, T. Ten Houte de Lange, P. M. Kooiman, T. van der Velde-Koerts, and P. Borst, “The human mdr3 gene encodes a novel P-glycoprotein homologue and gives rise to alternatively spliced mRNAs in liver,” The EMBO Journal, vol. 6, no. 11, pp. 3325–3331, 1987. View at Google Scholar · View at Scopus
  11. A. Moschetta, G. P. VanBerge-Henegouwen, P. Portincasa, G. Palasciano, A. K. Groen, and K. J. van Erpecum, “Sphingomyelin exhibits greatly enhanced protection compared with egg yolk phosphatidylcholine against detergent bile salts,” Journal of Lipid Research, vol. 41, no. 6, pp. 916–924, 2000. View at Google Scholar · View at Scopus
  12. J. A. Higgins and W. H. Evans, “Transverse organization of phospholipids across the bilayer of plasma-membrane subfractions of rat hepatocytes,” Biochemical Journal, vol. 174, no. 2, pp. 563–567, 1978. View at Google Scholar · View at Scopus
  13. D. Alvaro, A. Cantafora, A. F. Attili et al., “Follicular cysts, odontogenic keratocysts, and gorlin-goltz syndrome: some clinicopathologic aspects,” Comparative Biochemistry and Physiology B: Biochemistry, vol. 83, no. 3, pp. 551–554, 1986. View at Publisher · View at Google Scholar · View at Scopus
  14. J. J. M. Smit, A. H. Schinkel, R. P. J. Oude Elferink et al., “Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease,” Cell, vol. 75, no. 3, pp. 451–462, 1993. View at Publisher · View at Google Scholar · View at Scopus
  15. F. Lammert, D. Q.-H. Wang, S. Hillebrandt et al., “Spontaneous cholecysto- and hepatolithiasis in Mdr2-/- mice: a model for low phospholipid-associated cholelithiasis,” Hepatology, vol. 39, no. 1, pp. 117–128, 2004. View at Publisher · View at Google Scholar · View at Scopus
  16. R. P. J. Oude Elferink, R. Ottenhoff, M. van Wijland, J. J. M. Smit, A. H. Schinkel, and A. K. Groen, “Regulation of biliary lipid secretion by mdr2 P-glycoprotein in the mouse,” Journal of Clinical Investigation, vol. 95, no. 1, pp. 31–38, 1995. View at Publisher · View at Google Scholar · View at Scopus
  17. R. P. J. Oude Elferink, R. Ottenhoff, M. van Wijland, C. M. G. Frijters, C. van Nieuwkerk, and A. K. Groen, “Uncoupling of biliary phospholipid and cholesterol secretion in mice with reduced expression of mdr2 P-glycoprotein,” Journal of Lipid Research, vol. 37, no. 5, pp. 1065–1075, 1996. View at Google Scholar · View at Scopus
  18. M. C. Carey and D. M. Small, “The physical chemistry of cholesterol solubility in bile. Relationship to gallstone formation and dissolution in man,” Journal of Clinical Investigation, vol. 61, no. 4, pp. 998–1026, 1978. View at Publisher · View at Google Scholar · View at Scopus
  19. E. Jacquemin, J. M. DeVree, D. Cresteil et al., “The wide spectrum of multidrug resistance 3 deficiency: from neonatal cholestasis to cirrhosis of adulthood,” Gastroenterology, vol. 120, no. 6, pp. 1448–1458, 2001. View at Publisher · View at Google Scholar · View at Scopus
  20. J. Deleuze, E. Jacquemin, C. Dubuisson et al., “Defect of multidrug-resistance 3 gene expression in a subtype of progressive familial intrahepatic cholestasis,” Hepatology, vol. 23, no. 4, pp. 904–908, 1996. View at Publisher · View at Google Scholar · View at Scopus
  21. J. M. L. de Vree, E. Jacquemin, E. Sturm et al., “Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 1, pp. 282–287, 1998. View at Publisher · View at Google Scholar · View at Scopus
  22. J. Lucena, J. I. Herrero, J. Quiroga et al., “A multidrug resistance 3 gene mutation causing cholelithiasis, cholestasis of pregnancy, and adulthood biliary cirrhosis,” Gastroenterology, vol. 124, no. 4, pp. 1037–1042, 2003. View at Publisher · View at Google Scholar · View at Scopus
  23. O. Rosmorduc, B. Hermelin, P. Boelle, R. Parc, J. Taboury, and R. Poupon, “ABCB4 gene mutation-associated cholelithiasis in adults,” Gastroenterology, vol. 125, no. 2, pp. 452–459, 2003. View at Publisher · View at Google Scholar · View at Scopus
  24. D. Tougeron, G. Fotsing, V. Barbu, and M. Beauchant, “ABCB4/MDR3 gene mutations and cholangiocarcinomas,” Journal of Hepatology, vol. 57, no. 2, pp. 467–468, 2012. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Arrese and M. Ananthanarayanan, “The bile salt export pump: molecular properties, function and regulation,” Pflugers Archiv European Journal of Physiology, vol. 449, no. 2, pp. 123–131, 2004. View at Publisher · View at Google Scholar · View at Scopus
  26. L. Yu, J. Li-Hawkins, R. E. Hammer et al., “Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol,” Journal of Clinical Investigation, vol. 110, no. 5, pp. 671–680, 2002. View at Publisher · View at Google Scholar · View at Scopus
  27. L. Yu, R. E. Hammer, J. Li-Hawkins et al., “Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 25, pp. 16237–16242, 2002. View at Publisher · View at Google Scholar · View at Scopus
  28. D. M. Small, “Role of ABC transporters in secretion of cholesterol from liver into bile,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 1, pp. 4–6, 2003. View at Publisher · View at Google Scholar · View at Scopus
  29. T. Plösch, J. N. van der Veen, R. Havinga, N. C. A. Huijkman, V. W. Bloks, and F. Kuipers, “Abcg5/Abcg8-independent pathways contribute to hepatobiliary cholesterol secretion in mice,” The American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 291, no. 3, pp. G414–G423, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. S. Langheim, L. Yu, K. von Bergmann et al., “ABCG5 and ABCG8 require MDR2 for secretion of cholesterol into bile,” Journal of Lipid Research, vol. 46, no. 8, pp. 1732–1738, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. M. Pennings, R. B. Hildebrand, D. Ye et al., “Bone marrow-derived multidrug resistance protein ABCB4 protects against atherosclerotic lesion development in LDL receptor knockout mice,” Cardiovascular Research, vol. 76, no. 1, pp. 175–183, 2007. View at Publisher · View at Google Scholar · View at Scopus
  32. S. Ruetz and P. Gros, “Phosphatidylcholine translocase: a physiological role for the mdr2 gene,” Cell, vol. 77, no. 7, pp. 1071–1081, 1994. View at Publisher · View at Google Scholar · View at Scopus
  33. S. Ruetz and P. Gros, “Enhancement of Mdr2-mediated phosphatidylcholine translocation by the bile salt taurocholate. Implications for hepatic bile formation,” Journal of Biological Chemistry, vol. 270, no. 43, pp. 25388–25395, 1995. View at Publisher · View at Google Scholar · View at Scopus
  34. A. Van Helvoort, A. J. Smith, H. Sprong et al., “MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine,” Cell, vol. 87, no. 3, pp. 507–517, 1996. View at Publisher · View at Google Scholar · View at Scopus
  35. A. J. Smith, A. van Helvoort, G. van Meer et al., “MDR3 P-glycoprotein, a phosphatidylcholine translocase, transports several cytotoxic drugs and directly interacts with drags as judged by interference with nucleotide trapping,” Journal of Biological Chemistry, vol. 275, no. 31, pp. 23530–23539, 2000. View at Publisher · View at Google Scholar · View at Scopus
  36. J. Shoda, Y. Inada, A. Tsuji et al., “Bezafibrate stimulates canalicular localization of NBD-labeled PC in HepG2 cells by PPARα-mediated redistribution of ABCB4,” Journal of Lipid Research, vol. 45, no. 10, pp. 1813–1825, 2004. View at Publisher · View at Google Scholar · View at Scopus
  37. N. S. Ghonem, M. Ananthanarayanan, C. J. Soroka, and J. L. Boyer, “Peroxisome proliferator-activated receptor alpha activates human multidrug resistance transporter 3/ATP-binding cassette protein subfamily B4 transcription and increases rat biliary phosphatidylcholine secretion,” Hepatology, vol. 59, no. 3, pp. 1030–1042, 2014. View at Google Scholar
  38. S. Morita, A. Kobayashi, Y. Takanezawa et al., “Bile salt-dependent efflux of cellular phospholipids mediated by ATP binding cassette protein B4,” Hepatology, vol. 46, no. 1, pp. 188–199, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. D. M. Heuman, “Quantitative estimation of the hydrophilic-hydrophobic balance of mixed bile salt solutions,” Journal of Lipid Research, vol. 30, no. 5, pp. 719–730, 1989. View at Google Scholar · View at Scopus
  40. S. Morita, A. Takeuchi, and S. Kitagawa, “Functional analysis of two isoforms of phosphatidylethanolamine N-methyltransferase,” Biochemical Journal, vol. 432, no. 2, pp. 387–398, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. S. Morita, K. Soda, R. Teraoka, S. Kitagawa, and T. Terada, “Specific and sensitive enzymatic measurement of sphingomyelin in cultured cells,” Chemistry and Physics of Lipids, vol. 165, no. 5, pp. 571–576, 2012. View at Publisher · View at Google Scholar · View at Scopus
  42. S. Morita, T. Tsuda, M. Horikami, R. Teraoka, S. Kitagawa, and T. Terada, “Bile salt-stimulated phospholipid efflux mediated by ABCB4 localized in nonraft membranes,” Journal of Lipid Research, vol. 54, no. 5, pp. 1221–1230, 2013. View at Publisher · View at Google Scholar · View at Scopus
  43. K. Nagao, Y. Zhao, K. Takahashi, Y. Kimura, and K. Ueda, “Sodium taurocholate-dependent lipid efflux by ABCA1: effects of W590S mutation on lipid translocation and apolipoprotein A-I dissociation,” Journal of Lipid Research, vol. 50, no. 6, pp. 1165–1172, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. J. Gautherot, D. Delautier, M. A. Maubert et al., “Phosphorylation of ABCB4 impacts its function: insights from disease-causing mutations,” Hepatology, 2014. View at Publisher · View at Google Scholar
  45. T. Yoshikado, T. Takada, T. Yamamoto et al., “Itraconazole-induced cholestasis: Involvement of the inhibition of bile canalicular phospholipid translocator MDR3/ABCB4,” Molecular Pharmacology, vol. 79, no. 2, pp. 241–250, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. K. Kino, Y. Taguchi, K. Yamada, T. Komano, and K. Ueda, “Aureobasidin A, an antifungal cyclic depsipeptide antibiotic, is a substrate for both human MDR1 and MDR2/P-glycoproteins,” FEBS Letters, vol. 399, no. 1-2, pp. 29–32, 1996. View at Publisher · View at Google Scholar · View at Scopus
  47. Z. Duan, K. A. Brakora, and M. V. Seiden, “Inhibition of ABCB1 (MDR1) and ABCB4 (MDR3) expression by small interfering RNA and reversal resistance in human ovarian cancer cells,” Molecular Cancer Therapeutics, vol. 3, no. 7, pp. 833–838, 2004. View at Google Scholar · View at Scopus
  48. Z. E. Sauna and S. V. Ambudkar, “About a switch: how P-glycoprotein (ABCB1) harnesses the energy of ATP binding and hydrolysis to do mechanical work,” Molecular Cancer Therapeutics, vol. 6, no. 1, pp. 13–23, 2007. View at Publisher · View at Google Scholar · View at Scopus
  49. M. Ishigami, Y. Tominaga, K. Nagao et al., “ATPase activity of nucleotide binding domains of human MDR3 in the context of MDR1,” Biochimica et Biophysica Acta, vol. 1831, no. 4, pp. 683–690, 2013. View at Publisher · View at Google Scholar · View at Scopus
  50. Y. Ikebuchi, T. Takada, K. Ito et al., “Receptor for activated C-kinase 1 regulates the cellular localization and function of ABCB4,” Hepatology Research, vol. 39, no. 11, pp. 1091–1107, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. J. Gautherot, A. Durand-Schneider, D. Delautier et al., “Effects of cellular, chemical, and pharmacological chaperones on the rescue of a trafficking-defective mutant of the ATP-binding cassette transporter proteins ABCB1/ABCB4,” Journal of Biological Chemistry, vol. 287, no. 7, pp. 5070–5078, 2012. View at Publisher · View at Google Scholar · View at Scopus
  52. E. J. Andress, M. Nicolaou, and M. R. Romero, “Molecular mechanistic explanation for the spectrum of cholestatic disease caused by the S320F variant of ABCB4,” Hepatology, vol. 59, no. 5, pp. 1921–1931, 2014. View at Google Scholar
  53. R. Gordo-Gilart, S. Andueza, L. Hierro et al., “Functional analysis of ABCB4 mutations relates clinical outcomes of progressive familial intrahepatic cholestasis type 3 to the degree of MDR3 floppase activity,” Gut, 2014. View at Publisher · View at Google Scholar
  54. S. Orlowski, S. Martin, and A. Escargueil, “P-glycoprotein and “lipid rafts”: Some ambiguous mutual relationships (floating on them, building them or meeting them by chance?),” Cellular and Molecular Life Sciences, vol. 63, no. 9, pp. 1038–1059, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. K. Klappe, I. Hummel, D. Hoekstra, and J. W. Kok, “Lipid dependence of ABC transporter localization and function,” Chemistry and Physics of Lipids, vol. 161, no. 2, pp. 57–64, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. P. J. Quinn, “A lipid matrix model of membrane raft structure,” Progress in Lipid Research, vol. 49, no. 4, pp. 390–406, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. J. L. Macdonald and L. J. Pike, “A simplified method for the preparation of detergent-free lipid rafts,” Journal of Lipid Research, vol. 46, no. 5, pp. 1061–1067, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. E. Zaks-Makhina, H. Li, A. Grishin, V. Salvador-Recatala, and E. S. Levitan, “Specific and slow inhibition of the Kir2.1 K+ channel by gambogic acid,” The Journal of Biological Chemistry, vol. 284, no. 23, pp. 15432–15438, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. R. J. P. Dawson and K. P. Locher, “Structure of a bacterial multidrug ABC transporter,” Nature, vol. 443, no. 7108, pp. 180–185, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. S. G. Aller, J. Yu, A. Ward et al., “Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding,” Science, vol. 323, no. 5922, pp. 1718–1722, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. D. A. P. Gutmann, A. Ward, I. L. Urbatsch, G. Chang, and H. W. van Veen, “Understanding polyspecificity of multidrug ABC transporters: closing in on the gaps in ABCB1,” Trends in Biochemical Sciences, vol. 35, no. 1, pp. 36–42, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. A. J. Smith, J. L. Timmermans-Hereijgers, B. Roelofsen et al., “The human MDR3 P-glycoprotein promotes translocation of phosphatidylcholine through the plasma membrane of fibroblasts from transgenic mice,” FEBS Letters, vol. 354, no. 3, pp. 263–266, 1994. View at Publisher · View at Google Scholar · View at Scopus
  63. A. R. Crawford, A. J. Smith, V. C. Hatch, R. P. J. Oude Elferink, P. Borst, and J. M. Crawford, “Hepatic secretion of phospholipid vesicles in the mouse critically depends on mdr2 or MDR3 P-glycoprotein expression: visualization by electron microscopy,” Journal of Clinical Investigation, vol. 100, no. 10, pp. 2562–2567, 1997. View at Publisher · View at Google Scholar · View at Scopus
  64. A. Groen, M. R. Romero, C. Kunne et al., “Complementary functions of the flippase ATP8B1 and the floppase ABCB4 in maintaining canalicular membrane integrity,” Gastroenterology, vol. 141, no. 5, pp. 1927–1937, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. P. Borst, N. Zelcer, and A. van Helvoort, “ABC transporters in lipid transport,” Biochimica et Biophysica Acta—Molecular and Cell Biology of Lipids, vol. 1486, no. 1, pp. 128–144, 2000. View at Publisher · View at Google Scholar · View at Scopus