The role of ABC transporters in protecting cells from bilirubin toxicity

Current Pharmaceutical Design

Volumn 15, Issue 25, 2009, Pages 2884-2892

  Bellarosa, C ^a   Bortolussi, G ^a   Tiribelli, C ^a,b  

^a Centro Studi Fegato   (Italy)

^b UNIVERSITY OF TRIESTE   (Italy)

Author keywords

ATP binding cassette protein (ABC) protein; Bilirubin neurocytotoxicity; Multidrug resistance associated protein 1 (MRP1); Multidrug resistance associated protein 3 (MRP3); P glycoprotein (PGP); Unconiugated bilirubin

Indexed keywords

ABC TRANSPORTER; BILIRUBIN; GLYCOPROTEIN P; MULTIDRUG RESISTANCE PROTEIN 1; MULTIDRUG RESISTANCE PROTEIN 3; PREGNANE X RECEPTOR; TRANSMEMBRANE CONDUCTANCE REGULATOR;

AMINO ACID SEQUENCE; BASOLATERAL MEMBRANE; BINDING AFFINITY; BLOOD BRAIN BARRIER; CELL FUNCTION; CELL PROTECTION; CELL VIABILITY; CYTOTOXICITY; ENZYME ACTIVITY; ENZYME SPECIFICITY; GENE EXPRESSION REGULATION; GENE MUTATION; GENE SILENCING; HUMAN; IMMUNOHISTOCHEMISTRY; MEMBRANE VESICLE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN CONTENT; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN STRUCTURE; PROTEIN TRANSPORT; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; REVIEW; SEQUENCE HOMOLOGY; TISSUE DISTRIBUTION; TROPHOBLAST; UPREGULATION;

ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; BILIRUBIN; BIOLOGICAL TRANSPORT; CENTRAL NERVOUS SYSTEM DISEASES; HUMANS; HYPERBILIRUBINEMIA; HYPERBILIRUBINEMIA, NEONATAL; INFANT, NEWBORN; LIVER; MODELS, MOLECULAR; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; P-GLYCOPROTEIN; PROTEIN CONFORMATION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 70449409308     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161209789058246     Document Type: Review

References (96)

1. Dean M, Hamon Y, Chimini G. The human ATP-binding cassette (ABC) transporter superfamily. J Lipid Res 2001; 42(7): 1007-1017 (Pubitemid 32645780)
2. Muller M. Human ATP-Binding Cassette Transporters. http: //www nutrigene 4t com/humanabc htm [cited 2009 Jan 4];
3. Stefkova J, Poledne R, Hubacek JA. ATP-binding cassette (ABC) transporters in human metabolism and diseases. Physiol Res 2004; 53(3): 235-243 (Pubitemid 38797279)
4. Borst P, Elferink RO. Mammalian ABC transporters in health and disease. Annu Rev Biochem 2002; 71: 537-592 (Pubitemid 34800230)
5. Dean M, Rzhetsky A, Allikmets R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res 2001; 11(7): 1156-1166 (Pubitemid 32677289)
6. Deeley RG, Westlake C, Cole SP. Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Physiol Rev 2006; 86(3): 849-899 (Pubitemid 44033384)
7. Cole SP, Deeley RG. Multidrug resistance-associated protein: sequence correction. Science 1993; 260(5110): 879.
8. Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 1992; 258(5088): 1650-1654 (Pubitemid 23012438)
9. Loe DW, Almquist KC, Cole SP, Deeley RG. ATP-dependent 17 beta-estradiol 17-(beta-D-glucuronide) transport by multidrug resistance protein (MRP). Inhibition by cholestatic steroids. J Biol Chem 1996; 271(16): 9683-9689 (Pubitemid 26137375)
10. Salerno M, Petroutsa M, Garnier-Suillerot A. The MRP1-mediated effluxes of arsenic and antimony do not require arsenic-glutathione and antimony-glutathione complex formation. J Bioenerg Biomembr 2002; 34(2): 135-145 (Pubitemid 34477976)
11. Loe DW, Stewart RK, Massey TE, Deeley RG, Cole SP. ATP-dependent transport of aflatoxin B1 and its glutathione conjugates by the product of the multidrug resistance protein (MRP) gene. Mol Pharmacol 1997; 51(6): 1034-1041
12. Gekeler V, Ise W, Sanders KH, Ulrich WR, Beck J. The leukotriene LTD4 receptor antagonist MK571 specifically modulates MRP associated multidrug resistance. Biochem Biophys Res Commun 1995; 208(1): 345-352
13. Shen H, Paul S, Breuninger LM, Ciaccio PJ, Laing NM, Helt M, et al. Cellular and in vitro transport of glutathione conjugates by MRP. Biochemistry 1996; 35(18): 5719-5725
14. Leier I, Jedlitschky G, Buchholz U, Center M, Cole SP, Deeley RG, et al. ATP-dependent glutathione disulphide transport mediated by the MRP gene-encoded conjugate export pump. Biochem J 1996; 314 ( Pt 2): 433-437 (Pubitemid 26075650)
15. Jedlitschky G, Leier I, Buchholz U, Barnouin K, Kurz G, Keppler D. Transport of glutathione, glucuronate, and sulfate conjugates by the MRP gene-encoded conjugate export pump. Cancer Res 1996; 56(5): 988-994 (Pubitemid 26065391)
16. Heijn M, Hooijberg JH, Scheffer GL, Szabo G, Westerhoff HV, Lankelma J. Anthracyclines modulate multidrug resistance protein (MRP) mediated organic anion transport. Biochim Biophys Acta 1997; 1326(1): 12-22. (Pubitemid 27226806)
17. Loe DW, Almquist KC, Deeley RG, Cole SP. Multidrug resistance protein (MRP)-mediated transport of leukotriene C4 and chemotherapeutic agents in membrane vesicles. Demonstration of glutathione-dependent vincristine transport. J Biol Chem 1996; 271(16): 9675-9682 (Pubitemid 26137374)
18. Leslie EM, Deeley RG, Cole SP. Toxicological relevance of the multidrug resistance protein 1, MRP1 (ABCC1) and related transporters. Toxicology 2001; 167(1): 3-23.
19. Wijnholds J, deLange EC, Scheffer GL, van den Berg DJ, Mol CA, van d, V, et al. Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier. J Clin Invest 2000; 105(3): 279-285
20. Ostrow JD, Pascolo L, Tiribelli C. Reassessment of the unbound concentrations of unconjugated bilirubin in relation to neurotoxicity in vitro. Pediatr Res 2003; 54(1): 98-104. (Pubitemid 36736813)
21. Hansen TW. Kernicterus in term and near-term infants - the specter walks again. Acta Paediatr 2000; 89(10): 1155-1157 (Pubitemid 30809502)
22. Petrovic S, Pascolo L, Gallo R, Cupelli F, Ostrow JD, Goffeau A, et al. The products of YCF1 and YLL015w (BPT1) cooperate for the ATP-dependent vacuolar transport of unconjugated bilirubin in Saccharomyces cerevisiae. Yeast 2000; 16(6): 561-571 (Pubitemid 30201021)
23. Pascolo L, Fernetti C, Garcia-Mediavilla MV, Ostrow JD, Tiribelli C. Mechanisms for the transport of unconjugated bilirubin in human trophoblastic BeWo cells. FEBS Lett 2001; 495(1-2): 94-99 (Pubitemid 32367980)
24. Serrano MA, Bayon JE, Pascolo L, Tiribelli C, Ostrow JD, Gonzalez-Gallego J, et al. Evidence for carrier-mediated transport of unconjugated bilirubin across plasma membrane vesicles from human placental trophoblast. Placenta 2002; 23(7): 527-535 (Pubitemid 41110472)
25. Cekic D, Bellarosa C, Garcia-Mediavilla MV, Rigato I, Pascolo L, Ostrow JD, et al. Upregulation in the expression of multidrug resistance protein Mrp1 mRNA and protein by increased bilirubin production in rat. Biochem Biophys Res Commun 2003; 311(4): 891-896 (Pubitemid 37393401)
26. Strazielle N, Ghersi-Egea JF. Choroid plexus in the central nervous system: biology and physiopathology. J Neuropathol Exp Neurol 2000; 59(7): 561-574 (Pubitemid 30457787)
27. Rao VV, Dahlheimer JL, Bardgett ME, Snyder AZ, Finch RA, Sartorelli AC, et al. Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood-cerebrospinal-fluid drug-permeability barrier. Proc Natl Acad Sci USA 1999; 96(7): 3900-3905
28. Rigato I, Pascolo L, Fernetti C, Ostrow JD, Tiribelli C. The human multidrug-resistance-associated protein MRP1 mediates ATP-dependent transport of unconjugated bilirubin. Biochem J 2004; 383(Pt 2): 335-341 (Pubitemid 39446695)
29. Gennuso F, Fernetti C, Tirolo C, Testa N, L'Episcopo F, Caniglia S, et al. Bilirubin protects astrocytes from its own toxicity by inducing up-regulation and translocation of multidrug resistanceassociated protein 1 (Mrp1). Proc Natl Acad Sci USA 2004; 101(8): 2470-2475 (Pubitemid 38269335)
30. Calligaris S, Cekic D, Roca-Burgos L, Gerin F, Mazzone G, Ostrow JD, et al. Multidrug resistance associated protein 1 protects against bilirubin-induced cytotoxicity. FEBS Lett 2006; 580(5): 1355-1359 (Pubitemid 43222000)
31. Gourley GR. Bilirubin metabolism and kernicterus. Adv Pediatr 1997; 44: 173-229.
32. Dennery PA, Seidman DS, Stevenson DK. Neonatal hyperbilirubinemia. N Engl J Med 2001; 344(8): 581-590
33. Kaplan M, Hammerman C. Understanding and preventing severe neonatal hyperbilirubinemia: is bilirubin neurotoxity really a concern in the developed world? Clin Perinatol 2004; 31(3): 555-75, x.
34. Falcao AS, Bellarosa C, Fernandes A, Brito MA, Silva RF, Tiribelli C, et al. Role of multidrug resistance-associated protein 1 expression in the in vitro susceptibility of rat nerve cell to unconjugated bilirubin. Neuroscience 2007; 144(3): 878-888
35. Corich L, Aranda A, Carrassa L, Bellarosa C, Ostrow JD, Tiribelli C. The cytotoxic effect of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells is modulated by the expression level of MRP1 but not MDR1. Biochem J 2008; 417(1): 365-412
36. Belinsky MG, Bain LJ, Balsara BB, Testa JR, Kruh GD. Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins. J Natl Cancer Inst 1998; 90(22): 1735-1741
37. Kiuchi Y, Suzuki H, Hirohashi T, Tyson CA, Sugiyama Y. cDNA cloning and inducible expression of human multidrug resistance associated protein 3 (MRP3). FEBS Lett 1998; 433(1-2): 149-152 (Pubitemid 28386747)
38. Kool M, van der LM, de HM, Scheffer GL, de Vree JM, Smith AJ, et al. MRP3, an organic anion transporter able to transport anticancer drugs. Proc Natl Acad Sci USA 1999; 96(12): 6914-6919 (Pubitemid 29274984)
39. Zelcer N, van de WK, Hillebrand M, Sarton E, Kuil A, Wielinga PR, et al. Mice lacking multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide antinociception. Proc Natl Acad Sci USA 2005; 102(20): 7274-7279 (Pubitemid 40696369)
40. Zelcer N, Saeki T, Reid G, Beijnen JH, Borst P. Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J Biol Chem 2001; 276(49): 46400-46407 (Pubitemid 37370899)
41. Hirohashi T, Suzuki H, Sugiyama Y. Characterization of the transport properties of cloned rat multidrug resistance-associated protein 3 (MRP3). J Biol Chem 1999; 274(21): 15181-15185 (Pubitemid 129518857)
42. Zeng H, Liu G, Rea PA, Kruh GD. Transport of amphipathic anions by human multidrug resistance protein 3. Cancer Res 2000; 60(17): 4779-4784 (Pubitemid 30701488)
43. Belinsky MG, Dawson PA, Shchaveleva I, Bain LJ, Wang R, Ling V, et al. Analysis of the in vivo functions of Mrp3. Mol Pharmacol 2005; 68(1): 160-168
44. Lee YM, Cui Y, Konig J, Risch A, Jager B, Drings P, et al. Identification and functional characterization of the natural variant MRP3-Arg1297His of human multidrug resistance protein 3 (MRP3/ABCC3). Pharmacogenetics 2004; 14(4): 213-223 (Pubitemid 38530513)
45. Zelcer N, van de WK, de WR, Scheffer GL, Marschall HU, Wielinga PR, et al. Mice lacking Mrp3 (Abcc3) have normal bile salt transport, but altered hepatic transport of endogenous glucuronides. J Hepatol 2006; 44(4): 768-775
46. Borst P, de Wolf C, van de WK. Multidrug resistance-associated proteins 3, 4, and 5. Pflugers Arch 2007; 453(5): 661-673
47. Hirohashi T, Suzuki H, Takikawa H, Sugiyama Y. ATP-dependent transport of bile salts by rat multidrug resistance-associated protein 3 (Mrp3). J Biol Chem 2000; 275(4): 2905-2910 (Pubitemid 30082066)
48. Zelcer N, Saeki T, Bot I, Kuil A, Borst P. Transport of bile acids in multidrug-resistance-protein 3-overexpressing cells co-transfected with the ileal Na+-dependent bile-acid transporter. Biochem J 2003; 369(Pt 1): 23-30. (Pubitemid 36174121)
49. Chu XY, Huskey SE, Braun MP, Sarkadi B, Evans DC, Evers R. Transport of ethinylestradiol glucuronide and ethinylestradiol sulfate by the multidrug resistance proteins MRP1, MRP2, and MRP3. J Pharmacol Exp Ther 2004; 309(1): 156-164 (Pubitemid 38393126)
50. Konig J, Rost D, Cui Y, Keppler D. Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane. Hepatology 1999; 29(4): 1156-1163 (Pubitemid 29168750)
51. Scheffer GL, Kool M, de HM, de Vree JM, Pijnenborg AC, Bosman DK, et al. Tissue distribution and induction of human multidrug resistant protein 3. Lab Invest 2002; 82(2): 193-201. (Pubitemid 34160456)
52. Kool M, de Haas M, Scheffer GL, Scheper RJ, van Eijk MJ, Juijn JA, et al. Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines. Cancer Res 1997; 57(16): 3537-3547 (Pubitemid 27355505)
53. Lang T, Hitzl M, Burk O, Mornhinweg E, Keil A, Kerb R, et al. Genetic polymorphisms in the multidrug resistance-associated protein 3 (ABCC3, MRP3) gene and relationship to its mRNA and protein expression in human liver. Pharmacogenetics 2004; 14(3): 155-164 (Pubitemid 38373109)
54. Hirohashi T, Suzuki H, Ito K, Ogawa K, Kume K, Shimizu T, et al. Hepatic expression of multidrug resistance-associated protein-like proteins maintained in eisai hyperbilirubinemic rats. Mol Pharmacol 1998; 53(6): 1068-1075 (Pubitemid 28280450)
55. Zollner G, Fickert P, Silbert D, Fuchsbichler A, Marschall HU, Zatloukal K, et al. Adaptive changes in hepatobiliary transporter expression in primary biliary cirrhosis. J Hepatol 2003; 38(6): 717-727 (Pubitemid 36613336)
56. Donner MG, Keppler D. Up-regulation of basolateral multidrug resistance protein 3 (Mrp3) in cholestatic rat liver. Hepatology 2001; 34(2): 351-359 (Pubitemid 32702348)
57. Ogawa K, Suzuki H, Hirohashi T, Ishikawa T, Meier PJ, Hirose K, et al. Characterization of inducible nature of MRP3 in rat liver. Am J Physiol Gastrointest Liver Physiol 2000; 278(3): G438-G446. (Pubitemid 30152490)
58. Bohan A, Chen WS, Denson LA, Held MA, Boyer JL. Tumor necrosis factor alpha-dependent up-regulation of Lrh-1 and Mrp3(Abcc3) reduces liver injury in obstructive cholestasis. J Biol Chem 2003; 278(38): 36688-36698 (Pubitemid 37140001)
59. Ghanem CI, Ruiz ML, Villanueva SS, Luquita MG, Catania VA, Jones B, et al. Shift from biliary to urinary elimination of acetaminophen-glucuronide in acetaminophen-pretreated rats. J Pharmacol Exp Ther 2005; 315(3): 987-995 (Pubitemid 41635384)
60. Hitzl M, Klein K, Zanger UM, Fritz P, Nussler AK, Neuhaus P, et al. Influence of omeprazole on multidrug resistance protein 3 expression in human liver. J Pharmacol Exp Ther 2003; 304(2): 524-530 (Pubitemid 36152326)
61. Maher JM, Cheng X, Slitt AL, Dieter MZ, Klaassen CD. Induction of the multidrug resistance-associated protein family of transporters by chemical activators of receptor-mediated pathways in mouse liver. Drug Metab Dispos 2005; 33(7): 956-962 (Pubitemid 41002777)
62. Xiong H, Suzuki H, Sugiyama Y, Meier PJ, Pollack GM, Brouwer KL. Mechanisms of impaired biliary excretion of acetaminophen glucuronide after acute phenobarbital treatment or phenobarbital pretreatment. Drug Metab Dispos 2002; 30(9): 962-969 (Pubitemid 34894647)
63. Teng S, Jekerle V, Piquette-Miller M. Induction of ABCC3 (MRP3) by pregnane X receptor activators. Drug Metab Dispos 2003; 31(11): 1296-1299 (Pubitemid 37310315)
64. Cherrington NJ, Slitt AL, Maher JM, Zhang XX, Zhang J, Huang W, et al. Induction of multidrug resistance protein 3 (mrp3) in vivo is independent of constitutive androstane receptor. Drug Metab Dispos 2003; 31(11): 1315-1319
65. Inokuchi A, Hinoshita E, Iwamoto Y, Kohno K, Kuwano M, Uchiumi T. Enhanced expression of the human multidrug resistance protein 3 by bile salt in human enterocytes. A transcriptional control of a plausible bile acid transporter. J Biol Chem 2001; 276(50): 46822-46829 (Pubitemid 37373049)
66. Higuchi K, Kobayashi Y, Kuroda M, Tanaka Y, Itani T, Araki J, et al. Modulation of organic anion transporting polypeptide 1 and multidrug resistance protein 3 expression in the liver and kidney of Gunn rats. Hepatol Res 2004; 29(1): 60-66 (Pubitemid 38594513)
67. Iyanagi T, Watanabe T, Uchiyama Y. The 3-methylcholanthrene-inducible UDP-glucuronosyltransferase deficiency in the hyperbilirubinemic rat (Gunn rat) is caused by a -1 frameshift mutation. J Biol Chem 1989; 264(35): 21302-21307 (Pubitemid 20017951)
68. Chowdhury JR, Kondapalli R, Chowdhury NR. Gunn rat: a model for inherited deficiency of bilirubin glucuronidation. Adv Vet Sci Comp Med 1993; 37: 149-173
69. Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 1976; 455(1): 152-162
70. Gottesman MM, Pastan I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem 1993; 62: 385-427. (Pubitemid 23237876)
71. Schinkel AH. The physiological function of drug-transporting Pglycoproteins. Semin Cancer Biol 1997; 8(3): 161-170
72. Beaulieu E, Demeule M, Ghitescu L, Beliveau R. P-glycoprotein is strongly expressed in the luminal membranes of the endothelium of blood vessels in the brain. Biochem J 1997; 326 ( Pt 2): 539-544 (Pubitemid 27417234)
73. Gao B, Stieger B, Noe B, Fritschy JM, Meier PJ. Localization of the organic anion transporting polypeptide 2 (Oatp2) in capillary endothelium and choroid plexus epithelium of rat brain. J Histochem Cytochem 1999; 47(10): 1255-1264 (Pubitemid 29455921)
74. Schinkel AH, Smit JJ, van Tellingen O, Beijnen JH, Wagenaar E, van Deemter L, et al. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 1994; 77(4): 491-502. (Pubitemid 24153990)
75. Schinkel AH, Wagenaar E, Mol CA, van DL. P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J Clin Invest 1996; 97(11): 2517-2524 (Pubitemid 26187339)
76. Ayrton A, Morgan P. Role of transport proteins in drug absorption, distribution and excretion. Xenobiotica 2001; 31(8-9): 469-497 (Pubitemid 32826389)
77. Watchko JF, Daood MJ, Hansen TW. Brain bilirubin content is increased in P-glycoprotein-deficient transgenic null mutant mice. Pediatr Res 1998; 44(5): 763-766
78. Jette L, Murphy GF, Leclerc JM, Beliveau R. Interaction of drugs with P-glycoprotein in brain capillaries. Biochem Pharmacol 1995; 50(10): 1701-1709
79. Hanko E, Tommarello S, Watchko JF, Hansen TW. Administration of drugs known to inhibit P-glycoprotein increases brain bilirubin and alters the regional distribution of bilirubin in rat brain. Pediatr Res 2003; 54(4): 441-445 (Pubitemid 37159109)
80. Ostrow JD, Pascolo L, Tiribelli C. Reassessment of the unbound concentrations of unconjugated bilirubin in relation to neurotoxicity in vitro. Pediatr Res 2003; 54(6): 926.
81. Ostrow JD, Pascolo L, Brites D, Tiribelli C. Molecular basis of bilirubin-induced neurotoxicity. Trends Mol Med 2004; 10(2): 65-70.
82. Ballatori N, Dutczak WJ. Identification and characterization of high and low affinity transport systems for reduced glutathione in liver cell canalicular membranes. J Biol Chem 1994; 269(31): 19731-19737 (Pubitemid 24250883)
83. Watchko JF, Daood MJ, Mahmood B, Vats K, Hart C, Ahdab-Barmada M. P-glycoprotein and bilirubin disposition. J Perinatol 2001; 21 Suppl 1: S43-S47.
84. Zucker SD, Goessling W, Hoppin AG. Unconjugated bilirubin exhibits spontaneous diffusion through model lipid bilayers and native hepatocyte membranes. J Biol Chem 1999; 274(16): 10852-10862 (Pubitemid 29191067)
85. Granato A, Gores G, Vilei MT, Tolando R, Ferraresso C, Muraca M. Bilirubin inhibits bile acid induced apoptosis in rat hepatocytes. Gut 2003; 52(12): 1774-1778 (Pubitemid 37510402)
86. Borst P, Evers R, Kool M, Wijnholds J. The multidrug resistance protein family. Biochim Biophys Acta 1999; 1461(2): 347-357
87. Gazzin S, Strazielle N, Schmitt C, Fevre-Montange M, Ostrow JD, Tiribelli C, et al. Differential expression of the multidrug resistance-related proteins ABCb1 and ABCc1 between bloodbrain interfaces. J Comp Neurol 2008; 510(5): 497-507.
88. Falcao AS, Bellarosa C, Fernandes A, Brito MA, Silva RF, Tiribelli C, et al. Role of multidrug resistance-associated protein 1 expression in the in vitro susceptibility of rat nerve cell to unconjugated bilirubin. Neuroscience 2007; 144(3): 878-888
89. Falcao AS, Fernandes A, Brito MA, Silva RF, Brites D. Bilirubin-induced immunostimulant effects and toxicity vary with neural cell type and maturation state. Acta Neuropathol 2006; 112(1): 95-105. (Pubitemid 43942166)
90. Thaler MM. Substrate-induced conjugation of bilirubin in genetically deficient newborn rats. Science 1970; 170(957): 555-556
91. Xie W, Uppal H, Saini SP, Mu Y, Little JM, Radominska-Pandya A, et al. Orphan nuclear receptor-mediated xenobiotic regulation in drug metabolism. Drug Discov Today 2004; 9(10): 442-449 (Pubitemid 38510563)
92. Ostrow JD, Pascolo L, Brites D, Tiribelli C. Molecular basis of bilirubin-induced neurotoxicity. Trends Mol Med 2004; 10(2): 65-70.
93. Staudinger JL, Madan A, Carol KM, Parkinson A. Regulation of drug transporter gene expression by nuclear receptors. Drug Metab Dispos 2003; 31(5): 523-527 (Pubitemid 36444159)
94. Chow LM, Chan TH. Novel classes of dimer antitumour drug candidates. Curr Pharm Des 2009; 15(6): 659-674
95. Di YM, Li CG, Xue CC, Zhou SF. Clinical drugs that interact with St. John's wort and implication in drug development. Curr Pharm Des 2008; 14(17): 1723-1742
96. Parfenova H, Leffler CW. Cerebroprotective functions of HO-2. Curr Pharm Des 2008; 14(5): 443-453