Hepatobiliary transport in health and disease

Clinical Lipidology

Volumn 7, Issue 2, 2012, Pages 189-192

  Chan, Jeannie ^a   Vandeberg, John L ^a  

^a SOUTHWEST NATIONAL PRIMATE RESEARCH CENTER   (United States)

Author keywords

ATP binding cassette transporter; bile; canalicular membrane; cholestasis; cholesterol; P4 ATPase; phospholipids

Indexed keywords

ABC TRANSPORTER; ABC TRANSPORTER B11; ABC TRANSPORTER B4; CYCLOSPORIN A; EZETIMIBE; GLIBENCLAMIDE; PHOSPHATIDYLCHOLINE; PHOSPHATIDYLSERINE; PHYTOSTEROL; RIFAMPICIN; SITOSTEROL; UNCLASSIFIED DRUG; URSODEOXYCHOLIC ACID;

ABCB11 GENE; ABCB4 GENE; ABCC2 GENE; ABCG5 GENE; ABCG8 GENE; ARTICLE; ATP8B1 GENE; BENIGN RECURRENT INTRAHEPATIC CHOLESTASIS; BILE ACID SYNTHESIS; BILE SECRETION; DIET RESTRICTION; DISEASE SEVERITY; DUBIN JOHNSON SYNDROME; ENTEROHEPATIC CIRCULATION; GENE EXPRESSION; GENE FUNCTION; GENE LOCATION; GENETIC POLYMORPHISM; GENETIC PREDISPOSITION; HEPATOBILIARY SYSTEM; HETEROZYGOSITY; HUMAN; INTRAHEPATIC BILE DUCT; INTRAHEPATIC CHOLESTASIS; INTRAHEPATIC CHOLESTASIS OF PREGNANCY; LIPID BILAYER; LIPID METABOLISM; LIPOGENESIS; LIVER DISEASE; MARKER GENE; METABOLIC DISORDER; MISSENSE MUTATION; MUTATIONAL ANALYSIS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS; SITOSTEROLEMIA;

EID: 84860142620     PISSN: 17460875     EISSN: 17584302     Source Type: Journal    
DOI: 10.2217/clp.12.12     Document Type: Article

References (110)

1. Hofmann AF. Overview of bile secretion. In: Handbook of Physiology. Schultz SG (Ed.). American Physiological Society, MD, USA 549-566 (1989).
2. Trauner M, Boyer JL. Bile salt transporters: molecular characterization, function, and regulation. Physiol. Rev. 83(2), 633-671 (2003). (Pubitemid 36378680)
3. Klaassen CD, Aleksunes LM. Xenobiotic, bile acid, and cholesterol transporters: function and regulation. Pharmacol. Rev. 62(1), 1-96 (2010).
4. Folmer DE, Elferink RP, Paulusma CC. P4 ATPases-lipid fippases and their role in disease. Biochim. Biophys. Acta 1791(7), 628-635 (2009).
5. Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E. Progressive familial intrahepatic cholestasis. Orphanet J. Rare Dis. 4, 1 (2009).
6. Kidambi S, Patel SB. Sitosterolaemia: pathophysiology, clinical presentation and laboratory diagnosis. J. Clin. Pathol. 61(5), 588-594 (2008). (Pubitemid 351678209)
7. Shani M, Seligsohn U, Gilon E, Sheba C, Adam A. Dubin-Johnson syndrome in Israel. I. Clinical, laboratory, and genetic aspects of 101 cases. Q. J. Med. 39(156), 549-567 (1970).
8. Kajihara S, Hisatomi A, Mizuta T et al. A splice mutation in the human canalicular multispecifc organic anion transporter gene causes Dubin-Johnson syndrome. Biochem. Biophys. Res. Commun. 253(2), 454-457 (1998). (Pubitemid 29026723)
9. Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72, 137-174 (2003). (Pubitemid 36930444)
10. Marschall HU, Matern H, Sjövall J, Matern S. Conjugation of bile acids. In: Bile Acids-Cholestasis-Gallstones: Advances in Basic and Clinical Bile Acid Research. Fromm H, Leuschner U (Eds). Kluwer, Dordrecht, The Netherlands, 13-22 (1996).
11. Hofmann AF. Bile acids: trying to understand their chemistry and biology with the hope of helping patients. Hepatology 49(5), 1403-1418 (2009).
12. Suchy FJ, Sippel CJ, Ananthanarayanan M. Bile acid transport across the hepatocyte canalicular membrane. FASEB J. 11(4), 199-205 (1997). (Pubitemid 27118320)
13. Dawson PA, Lan T, Rao A. Bile acid transporters. J. Lipid Res. 50(12), 2340-2357 (2009).
14. Noe J, Stieger B, Meier PJ. Functional expression of the canalicular bile salt export pump of human liver. Gastroenterology 123(5), 1659-1666 (2002). (Pubitemid 35231665)
15. Hayashi H, Takada T, Suzuki H, Onuki R, Hofmann AF, 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 1738(1-3), 54-62 (2005). (Pubitemid 43122130)
16. 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. 314(2), 876-882 (2005). (Pubitemid 41043874)
17. Strautnieks SS, Bull LN, Knisely AS et al. A gene encoding a liver-specifc ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat. Genet. 20(3), 233-238 (1998). (Pubitemid 28507666)
18. Jansen PL, Strautnieks SS, Jacquemin E et al. Hepatocanalicular bile salt export pump defciency in patients with progressive familial intrahepatic cholestasis. Gastroenterology 117(6), 1370-1379 (1999).
19. Parks DJ, Blanchard SG, Bledsoe RK et al. Bile acids: natural ligands for an orphan nuclear receptor. Science 284(5418), 1365-1368 (1999). (Pubitemid 29289664)
20. Lew JL, Zhao A, Yu J et al. The farnesoid X receptor controls gene expression in a ligand-and promoter-selective fashion. J. Biol. Chem. 279(10), 8856-8861 (2004). (Pubitemid 38295944)
21. Ananthanarayanan M, Balasubramanian N, Makishima M, Mangelsdorf DJ, Suchy FJ. Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile acid receptor. J. Biol. Chem. 276(31), 28857-28865 (2001).
22. Sinal CJ, Tohkin M, Miyata M, Ward JM, Lambert G, Gonzalez FJ. Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 102(6), 731-744 (2000).
23. Lam P, Soroka CJ, Boyer JL. The bile salt export pump: clinical and experimental aspects of genetic and acquired cholestatic liver disease. Semin. Liver Dis. 30(2), 125-133 (2010).
24. Pawlikowska L, Strautnieks S, Jankowska I et al. Differences in presentation and progression between severe FIC1 and BSEP defciencies. J. Hepatol. 53(1), 170-178 (2010).
25. Morotti RA, Suchy FJ, Magid MS. Progressive familial intrahepatic cholestasis (PFIC) type 1, 2, and 3: a review of the liver pathology fndings. Semin. Liver Dis. 31(1), 3-10 (2011).
26. Strautnieks SS, Byrne J A, Pawlikowska L et al. Severe bile salt export pump defciency: 82 different ABCB11 mutations in 109 families. Gastroenterology 134(4), 1203-1214 (2008).
27. van Mil SW, van der Woerd WL, van der Brugge G et al. Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11. Gastroenterology 127(2), 379-384 (2004). (Pubitemid 39091885)
28. Stieger B. Role of the bile salt export pump, BSEP, in acquired forms of cholestasis. Drug Metab. Rev. 42(3), 437-445 (2010).
29. Kennedy EP, Weiss SB. The function of cytidine coenzymes in the biosynthesis of phospholipides. J. Biol. Chem. 222(1), 193-214 (1956).
30. Vance DE, Ridgway ND. The methylation of phosphatidylethanolamine. Prog. Lipid Res. 27(1), 61-79 (1988).
31. Portal I, Clerc T, Sbarra V et al. Importance of high-density lipoprotein-phosphatidylcholine in secretion of phospholipid and cholesterol in bile. Am. J. Physiol. 264(6 Pt 1), G1052-6 (1993). (Pubitemid 23196808)
32. Minahk C, Kim KW, Nelson R, Trigatti B, Lehner R, Vance DE. Conversion of low density lipoprotein-associated phosphatidylcholine to triacylglycerol by primary hepatocytes. J. Biol. Chem. 283(10), 6449-6458 (2008).
33. Oude Elferink RP, Paulusma CC. Function and pathophysiological importance of ABCB4 (MDR3 P-glycoprotein). Pfugers Arch. 453(5), 601-610 (2007). (Pubitemid 46192533)
34. Gros P, Raymond M, Bell J, Housman D. Cloning and characterization of a second member of the mouse Mdr gene family. Mol. Cell. Biol. 8(7), 2770-2778 (1988).
35. Smit J J, Schinkel AH, Oude Elferink RP 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 75 (3), 451-462 (1993). (Pubitemid 23335071)
36. Smith AJ, de Vree JM, Ottenhoff R, Oude Elferink RP, Schinkel AH, Borst P. Hepatocyte-specifc expression of the human MDR3 P-glycoprotein gene restores the biliary phosphatidylcholine excretion absent in Mdr2 (-/-) mice. Hepatology 28(2), 530-536 (1998). (Pubitemid 28363683)
37. Morita SY, Kobayashi A, Takanezawa Y et al. Bile salt-dependent effux of cellular phospholipids mediated by ATP binding cassette protein B4. Hepatology 46(1), 188-199 (2007). (Pubitemid 47171936)
38. Ikebuchi Y, Takada T, Ito K et al. Receptor for activated C-kinase 1 regulates the cellular localization and function of ABCB4. Hepatol. Res. 39(11), 1091-1107 (2009).
39. Groen A, Romero MR, Kunne C et al. Complementary functions of the fippase ATP8B1 and the foppase ABCB4 in maintaining canalicular membrane integrity Gastroenterology 141(5), 1927-37.e1-4 (2011).
40. Lincke CR, Smit JJ, van der Velde-Koerts T, Borst P. Structure of the human MDR3 gene and physical mapping of the human MDR locus. J. Biol. Chem. 266(8), 5303-5310 (1991). (Pubitemid 21909491)
41. Smit JJ, Schinkel AH, Mol CA et al. Tissue distribution of the human MDR3 P-glycoprotein. Lab. Invest. 71(5), 638-649 (1994). (Pubitemid 24374570)
42. Huang L, Zhao A, Lew JL et al. Farnesoid X receptor activates transcription of the phospholipid pump MDR3. J. Biol. Chem. 278(51), 51085-51090 (2003). (Pubitemid 38020343)
43. Gonzales E, Davit-Spraul A, Baussan C, Buffet C, Maurice M, Jacquemin E. Liver diseases related to MDR3 (ABCB4) gene defciency. Front. Biosci. 14, 4242-4256 (2009).
44. Holthuis JC, Levine TP. Lipid traffc: foppy drives and a superhighway. Nat. Rev. Mol. Cell Biol. 6(3), 209-220 (2005). (Pubitemid 40314922)
45. Oude Elferink RP, Paulusma CC, Groen AK. Hepatocanalicular transport defects: pathophysiologic mechanisms of rare diseases. Gastroenterology 130(3), 908-925 (2006). (Pubitemid 43374538)
46. Vance JE, Steenbergen R. Metabolism and functions of phosphatidylserine. Prog. Lipid Res. 44(4), 207-234 (2005). (Pubitemid 40973811)
47. Bergo MO, Gavino BJ, Steenbergen R et al. Defning the importance of phosphatidylserine synthase 2 in mice. J. Biol. Chem. 277(49), 47701-47708 (2002). (Pubitemid 36159293)
48. Arikketh D, Nelson R, Vance JE. Defning the importance of phosphatidylserine synthase-1 (PSS1): unexpected viability of PSS1-defcient mice. J. Biol. Chem. 283(19), 12888-12897 (2008).
49. Klomp LW, Vargas JC, van Mil SW et al. Characterization of mutations in ATP8B1 associated with hereditary cholestasis. Hepatology 40(1), 27-38 (2004). (Pubitemid 38868920)
50. Paulusma CC, Oude Elferink RP. The type 4 subfamily of P-type ATPases, putative aminophospholipid translocases with a role in human disease. Biochim. Biophys. Acta 1741(1-2), 11-24 (2005). (Pubitemid 40824985)
51. Bull LN, van Eijk MJ, Pawlikowska L et al. A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis. Nat. Genet. 18(3), 219-224 (1998). (Pubitemid 28117258)
52. Paulusma CC, Folmer DE, Ho-Mok KS et al. ATP8B1 requires an accessory protein for endoplasmic reticulum exit and plasma membrane lipid fippase activity. Hepatology 47(1), 268-278 (2008). (Pubitemid 351171064)
53. Bryde S, Hennrich H, Verhulst PM, Devaux PF, Lenoir G, Holthuis JC. CDC50 proteins are critical components of the human class-1 P4-ATPase transport machinery. J. Biol. Chem. 285(52), 40562-40572 (2010).
54. Paulusma CC, Groen A, Kunne C et al. Atp8b1 defciency in mice reduces resistance of the canalicular membrane to hydrophobic bile salts and impairs bile salt transport. Hepatology 44(1), 195-204 (2006). (Pubitemid 44049152)
55. Cai SY, Gautam S, Nguyen T, Soroka CJ, Rahner C, Boyer JL. ATP8B1 defciency disrupts the bile canalicular membrane bilayer structure in hepatocytes, but FXR expression and activity are maintained. Gastroenterology 136(3), 1060-1069 (2009).
56. Clayton RJ, Iber FL, Ruebner BH, McKusick VA. Byler disease. Fatal familial intrahepatic cholestasis in an Amish kindred. Am. J. Dis. Child. 117(1), 112-124 (1969).
57. Klomp LW, Bull LN, Knisely AS et al. A missense mutation in FIC1 is associated with Greenland familial cholestasis. Hepatology 32(6), 1337-1341 (2000).
58. Paulusma CC, Elferink RP, Jansen PL. Progressive familial intrahepatic cholestasis type 1. Semin. Liver Dis. 30(2), 117-124 (2010).
59. Folmer DE, van der Mark VA, Ho-Mok KS, Oude Elferink RP, Paulusma CC. Differential effects of progressive familial intrahepatic cholestasis type 1 and benign recurrent intrahepatic cholestasis type 1 mutations on canalicular localization of ATP8B1. Hepatology 50(5), 1597-1605 (2009).
60. Bull LN, Carlton VE, Stricker NL et al. Genetic and morphological fndings in progressive familial intrahepatic cholestasis (Byler disease [PFIC-1] and Byler syndrome): evidence for heterogeneity. Hepatology 26(1), 155-164 (1997). (Pubitemid 27280320)
61. Mullenbach R, Bennett A, Tetlow N et al. ATP8B1 mutations in British cases with intrahepatic cholestasis of pregnancy. Gut 54(6), 829-834 (2005). (Pubitemid 40732102)
62. Painter JN, Savander M, Ropponen A et al. Sequence variation in the ATP8B1 gene and intrahepatic cholestasis of pregnancy. Eur. J. Hum. Genet. 13(4), 435-439 (2005). (Pubitemid 40520934)
63. Paulusma CC, de Waart DR, Kunne C, Mok KS, Elferink R P. Activity of the bile salt export pump (ABCB11) is critically dependent on canalicular membrane cholesterol content. J. Biol. Chem. 284(15), 9947-9954 (2009).
64. Stapelbroek JM, vanErpecum KJ, Klomp LW, Houwen RH. Liver disease associated with canalicular transport defects: current and future therapies. J. Hepatol. 52(2), 258-271 (2010).
65. Repa JJ, Mangelsdorf DJ. The role of orphan nuclear receptors in the regulation of cholesterol homeostasis. Annu. Rev. Cell Dev. Biol. 16, 459-481 (2000). (Pubitemid 32037514)
66. Botham KM, Bravo E. The role of lipoprotein cholesterol in biliary steroid secretion. Studies with in vivo experimental models. Prog. Lipid Res. 34(1), 71-97 (1995).
67. Schwartz CC, Halloran LG, Vlahcevic ZR, Gregory DH, Swell L. Preferential utilization of free cholesterol from high-density lipoproteins for biliary cholesterol secretion in man. Science 200(4337), 62-64 (1978). (Pubitemid 8302933)
68. Hillebrant CG, Nyberg B, Einarsson K, Eriksson M. The effect of plasma low density lipoprotein apheresis on the hepatic secretion of biliary lipids in humans. Gut 41(5), 700-704 (1997).
69. Salen G, Shefer S, Nguyen L, Ness GC, Tint GS, Shore V. Sitosterolemia. J. Lipid Res. 33(7), 945-955 (1992).
70. Heinemann T, Axtmann G, von Bergmann K. Comparison of intestinal absorption of cholesterol with different plant sterols in man. Eur. J. Clin. Invest. 23(12), 827-831 (1993). (Pubitemid 24015625)
71. Bosner MS, Lange LG, Stenson WF, Ostlund RE Jr. Percent cholesterol absorption in normal women and men quantifed with dual stable isotopic tracers and negative ion mass spectrometry. J. Lipid Res. 40(2), 302-308 (1999). (Pubitemid 29069805)
72. Patel SB, Salen G, Hidaka H et al. Mapping a gene involved in regulating dietary cholesterol absorption. The sitosterolemia locus is found at chromosome 2p21. J. Clin. Invest. 102(5), 1041-1044 (1998). (Pubitemid 28419249)
73. Berge KE, Tian H, Graf GA et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 290(5497), 1771-1775 (2000). (Pubitemid 32004809)
74. Lee MH, Lu K, Hazard S et al. Identifcation of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nat. Genet. 27(1), 79-83 (2001). (Pubitemid 32044523)
75. Lu K, Lee MH, Hazard S et al. Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively. Am. J. Hum. Genet. 69(2), 278-290 (2001). (Pubitemid 32695201)
76. Graf GA, Yu L, Li WP et al. ABCG5 and ABCG8 are obligate heterodimers for protein traffcking and biliary cholesterol excretion. J. Biol. Chem. 278(48), 48275-48282 (2003). (Pubitemid 37523283)
77. Klett EL, Lee MH, Adams DB, Chavin KD, Patel SB. Localization of ABCG5 and ABCG8 proteins in human liver, gall bladder and intestine. BMC Gastroenterol. 4, 21 (2004).
78. Kosters A, Kunne C, Looije N, Patel SB, Oude Elferink RP, Groen AK. The mechanism of ABCG5/ABCG8 in biliary cholesterol secretion in mice. J. Lipid Res. 47(9), 1959-1966 (2006). (Pubitemid 44401983)
79. Small DM. Role of ABC transporters in secretion of cholesterol from liver into bile. Proc. Natl Acad. Sci. USA 100(1), 4-6 (2003). (Pubitemid 36078019)
80. Bhattacharyya AK, Connor WE. Beta-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters. J. Clin. Invest. 53(4), 1033-1043 (1974).
81. Lutjohann D, Bjorkhem I, Beil UF, von Bergmann K. Sterol absorption and sterol balance in phytosterolemia evaluated by deuterium-labeled sterols: effect of sitostanol treatment. J. Lipid Res. 36(8), 1763-1773 (1995).
82. Miettinen TA, Klett EL, Gylling H, Isoniemi H, Patel SB. Liver transplantation in a patient with sitosterolemia and cirrhosis. Gastroenterology 130(2), 542-547 (2006). (Pubitemid 43202050)
83. Tsubakio-Yamamoto K, Nishida M, Nakagawa-Toyama Y, Masuda D, Ohama T, Yamashita S. Current therapy for patients with sitosterolemia-effect of ezetimibe on plant sterol metabolism. J. Atheroscler. Thromb. 17(9), 891-900 (2010).
84. Salen G, Starc T, Sisk CM, Patel SB. Intestinal cholesterol absorption inhibitor ezetimibe added to cholestyramine for sitosterolemia and xanthomatosis. Gastroenterology 130(6), 1853-1857 (2006). (Pubitemid 43668834)
85. Lutjohann D, von Bergmann K, Sirah W et al. Long-term effcacy and safety of ezetimibe 10 mg in patients with homozygous sitosterolemia: a 2-year, open-label extension study. Int. J. Clin. Pract. 62(10), 1499-1510 (2008).
86. Altmann SW, Davis HR Jr, Zhu LJ et al. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science 303(5661), 1201-1204 (2004). (Pubitemid 38233587)
87. Davis HR Jr, Zhu LJ, Hoos LM et al. Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis. J. Biol. Chem. 279(32), 33586-33592 (2004). (Pubitemid 39063007)
88. Garcia-Calvo M, Lisnock J, Bull HG et al. The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc. Natl Acad. Sci. USA 102(23), 8132-8137 (2005). (Pubitemid 40800055)
89. Davies JP, Scott C, Oishi K, Liapis A, Ioannou YA. Inactivation of NPC1L1 causes multiple lipid transport defects and protects against diet-induced hypercholesterolemia. J. Biol. Chem. 280(13), 12710-12720 (2005).
90. Temel RE, Tang W, Ma Y et al. Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe. J. Clin. Invest. 117(7), 1968-1978 (2007). (Pubitemid 47036331)
91. Kamisako T, Leier I, Cui Y et al. Transport of monoglucuronosyl and bisglucuronosyl bilirubin by recombinant human and rat multidrug resistance protein 2. Hepatology 30(2), 485-490 (1999). (Pubitemid 29357515)
92. Taniguchi K, Wada M, Kohno K et al. A human canalicular multispecifc organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation. Cancer Res. 56(18), 4124-4129 (1996). (Pubitemid 26305002)
93. Toh S, Wada M, Uchiumi T et al. Genomic structure of the canalicular multispecifc organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome. Am. J. Hum. Genet. 64(3), 739-746 (1999). (Pubitemid 30460416)
94. Tsujii H, Konig J, Rost D, Stockel B, Leuschner U, Keppler D. Exon-intron organization of the human multidrug-resistance protein 2 (MRP2) gene mutated in Dubin-Johnson syndrome. Gastroenterology 117(3), 653-660 (1999). (Pubitemid 29409252)
95. Jemnitz K, Heredi-Szabo K, Janossy J, Ioja E, Vereczkey L, Krajcsi P. ABCC2/Abcc2: a multispecifc transporter with dominant excretory functions. Drug Metab. Rev. 42(3), 402-436 (2010).
96. Schaub TP, Kartenbeck J, Konig J et al. Expression of the MRP2 gene-encoded conjugate export pump in human kidney proximal tubules and in renal cell carcinoma. J. Am. Soc. Nephrol. 10(6), 1159-1169 (1999). (Pubitemid 29246980)
97. Fromm MF, Kauffmann HM, Fritz P et al. The effect of rifampin treatment on intestinal expression of human MRP transporters. Am. J. Pathol. 157(5), 1575-1580 (2000).
98. Nies AT, Konig J, Pfannschmidt M, Klar E, Hofmann WJ, Keppler D. Expression of the multidrug resistance proteins MRP2 and MRP3 in human hepatocellular carcinoma. Int. J. Cancer 94(4), 492-499 (2001).
99. Sandusky GE, Mintze KS, Pratt SE, Dantzig AH. Expression of multidrug resistance-associated protein 2 (MRP2) in normal human tissues and carcinomas using tissue microarrays. Histopathology 41(1), 65-74 (2002). (Pubitemid 34779683)
100. Dubin IN, Johnson FB. Chronic idiopathic jaundice with unidentifed pigment in liver cells; a new clinicopathologic entity with a report of 12 cases. Medicine (Baltimore) 33(3), 155-197 (1954).
101. Rastogi A, Krishnani N, Pandey R. Dubin-Johnson syndrome-a clinicopathologic study of twenty cases. Indian J. Pathol. Microbiol. 49(4), 500-504 (2006). (Pubitemid 44951807)
102. Donner MG, Keppler D. Up-regulation of basolateral multidrug resistance protein 3 (Mrp3) in cholestatic rat liver. Hepatology 34(2), 351-359 (2001). (Pubitemid 32702348)
103. Nisa AU, Ahmad Z. Dubin-Johnson syndrome. J. Coll. Physicians Surg. Pak. 18(3), 188-189 (2008). (Pubitemid 351676199)
104. Nies AT, Keppler D. The apical conjugate effux pump ABCC2 (MRP2). Pfugers Arch. 453(5), 643-659 (2007). (Pubitemid 46192536)
105. Welch EM, Barton ER, Zhuo J et al. PTC124 targets genetic disorders caused by nonsense mutations. Nature 447(7140), 87-91 (2007). (Pubitemid 46685839)
106. van der Velden LM, Stapelbroek JM, Krieger E et al. Folding defects in P-type ATP 8B1 associated with hereditary cholestasis are ameliorated by 4-phenylbutyrate. Hepatology 51(1), 286-296 (2010).
107. 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 45(6), 1506-1516 (2007). (Pubitemid 46918335)
108. Collin J, Lako M. Concise review: putting a fnger on stem cell biology: zinc fnger nuclease-driven targeted genetic editing in human pluripotent stem cells. Stem Cells 29(7), 1021-1033 (2011).
109. Miller JC, Tan S, Qiao G et al. A TALE nuclease architecture for effcient genome editing. Nat. Biotechnol. 29(2), 143-148 (2011).
110. Ellis BL, Hirsch ML, Porter SN, Samulski RJ, Porteus MH. Zinc-fnger nuclease-mediated gene correction using single A AV vector transduction and enhancement by Food and Drug Administration-approved drugs. Gene Ther. doi:10.1038/gt.2011.211 (2012) (Epub ahead of print).