Transcriptional regulation of cytochrome P450 genes by the nuclear receptor hepatocyte nuclear factor 4-alpha

Current Drug Metabolism

Volumn 10, Issue 5, 2009, Pages 508-519

  Jover, Ramiro ^a,b,c   Moya, Marta ^a   Gómez Lechón, M José ^a,b  

^a HOSPITAL UNIVERSITARIO LA FE   (Spain)

^b INSTITUTO DE SALUD CARLOS III   (Spain)

^c UNIVERSITY OF VALENCIA   (Spain)

Author keywords

CYP induction; Cytochrome P450; Drug metabolism; Hepatocyte nuclear factor 4 alpha; Liver pathophysiology; Transcription regulation

Indexed keywords

CELL NUCLEUS RECEPTOR; CHICKEN OVALBUMIN UPSTREAM PROMOTER TRANSCRIPTION FACTOR; CYTOCHROME P450; CYTOCHROME P450 2B; CYTOCHROME P450 2C; CYTOCHROME P450 2D; CYTOCHROME P450 3A; DEXAMETHASONE; FARNESOID X RECEPTOR; GLUCOCORTICOID; GLUCOCORTICOID RECEPTOR; HEPATOCYTE NUCLEAR FACTOR 4ALPHA; LIVER X RECEPTOR; NITRIC OXIDE; OKADAIC ACID; PHENOBARBITAL; PREGNANE X RECEPTOR; PROTEIN TYROSINE PHOSPHATASE SHP; RIFAMPICIN; SHORT HETERODIMER PARTNER; UNCLASSIFIED DRUG; DRUG; HEPATOCYTE NUCLEAR FACTOR 4;

DIABETES MELLITUS; DRUG METABOLISM; GENE ACTIVATION; GENE ACTIVITY; GENE EXPRESSION; HUMAN; INFLAMMATION; LIVER CELL; LIVER FUNCTION; MOLECULAR INTERACTION; NONALCOHOLIC FATTY LIVER; NONHUMAN; PATHOPHYSIOLOGY; REVIEW; SEX DIFFERENTIATION; TRANSCRIPTION REGULATION; ANIMAL; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; GENETICS; LIVER; LIVER DISEASE; METABOLISM;

ANIMALS; CYTOCHROME P-450 ENZYME SYSTEM; GENE EXPRESSION REGULATION; HEPATOCYTE NUCLEAR FACTOR 4; HUMANS; LIVER; LIVER DISEASES; PHARMACEUTICAL PREPARATIONS; TRANSCRIPTION, GENETIC;

EID: 70350771206     PISSN: 13892002     EISSN: None     Source Type: Journal    
DOI: 10.2174/138920009788898000     Document Type: Review

References (85)

1. Sladek, F.M. Orphan receptor HNF-4 and liver-specific gene expression. Receptor, 1993, 3(3), 223-232.
2. Watt, A.J.; Garrison, W.D.; Duncan, S.A. HNF4: a central regulator of hepatocyte differentiation and function. Hepatology, 2003, 37(6), 1249-1253.
3. Sladek, F.M.; Zhong, W.M.; Lai, E.; Darnell, J.E., Jr. Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. Genes Dev., 1990, 4(12B), 2353-2365.
4. Sladek, F. Desperately seeking...something. Mol. Cell, 2002, 10(2), 219-221.
5. Wisely, G.B.; Miller, A.B.; Davis, R.G.; Thornquest, A.D., Jr.; Johnson, R.; Spitzer, T.; Sefler, A.; Shearer, B.; Moore, J.T.; Willson, T.M.; Williams, S.P. Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds fatty acids. Structure, 2002, 10(9), 1225-1234.
6. Dhe-Paganon, S.; Duda, K.; Iwamoto, M.; Chi, Y.I.; Shoelson, S.E. Crystal structure of the HNF4 alpha ligand binding domain in complex with endogenous fatty acid ligand. J. Biol. Chem., 2002, 277(41), 37973-37976.
7. Duda, K.; Chi, Y.I.; Shoelson, S.E. Structural basis for HNF-4alpha activation by ligand and coactivator binding. J. Biol. Chem., 2004, 279(22), 23311-23316. (Pubitemid 38685640)
8. Gonzalez, F.J. Regulation of hepatocyte nuclear factor 4 alpha-mediated transcription. Drug Metab. Pharmacokinet., 2008, 23(1), 2-7.
9. Venepally, P.; Chen, D.; Kemper, B. Transcriptional regulatory elements for basal expression of cytochrome P450IIC genes. J. Biol. Chem., 1992, 267(24), 17333-17338.
10. Chen, D.; Park, Y.; Kemper, B. Differential protein binding and transcriptional activities of HNF-4 elements in three closely related CYP2C genes. DNA Cell Biol., 1994, 13(7), 771-779. (Pubitemid 24290006)
11. Chen, D.; Lepar, G.; Kemper, B. A transcriptional regulatory element common to a large family of hepatic cytochrome P450 genes is a functional binding site of the orphan receptor HNF-4. J. Biol. Chem., 1994, 269(7), 5420-5427. (Pubitemid 24239541)
12. Jover, R.; Bort, R.; Gomez-Lechon, M.J.; Castell, J.V. Cytochrome P450 regulation by hepatocyte nuclear factor 4 in human hepatocytes: a study using adenovirus-mediated antisense targeting. Hepatology, 2001, 33(3), 668-675.
13. Kamiyama, Y.; Matsubara, T.; Yoshinari, K.; Nagata, K.; Kamimura, H.; Yamazoe, Y. Role of human hepatocyte nuclear factor 4alpha in the expression of drug-metabolizing enzymes and transporters in human hepatocytes assessed by use of small interfering RNA. Drug Metab. Pharmacokinet., 2007, 22(4), 287-298.
14. Naiki, T.; Nagaki, M.; Shidoji, Y.; Kojima, H.; Moriwaki, H. Functional activity of human hepatoma cells transfected with adenovirus-mediated hepatocyte nuclear factor (HNF)-4 gene. Cell Transplant., 2004, 13(4), 393-403. (Pubitemid 39163084)
15. Inoue, K.; Negishi, M. Nuclear receptor CAR requires early growth response 1 to activate the human cytochrome P450 2B6 gene. J. Biol. Chem., 2008, 283(16), 10425-10432.
16. Li, T.; Chiang, J.Y. Rifampicin induction of CYP3A4 requires pregnane X receptor cross talk with hepatocyte nuclear factor 4alpha and coactivators, and suppression of small heterodimer partner gene expression. Drug Metab. Dispos., 2006, 34(5), 756-764.
17. Chen, Y.; Kissling, G.; Negishi, M.; Goldstein, J.A. The nuclear receptors constitutive androstane receptor and pregnane X receptor cross-talk with hepatic nuclear factor 4alpha to synergistically activate the human CYP2C9 promoter. J. Pharmacol. Exp. Ther., 2005, 314(3), 1125-1133. (Pubitemid 41205977)
18. Tirona, R.G.; Lee, W.; Leake, B.F.; Lan, L.B.; Cline, C.B.; Lamba, V.; Parviz, F.; Duncan, S.A.; Inoue, Y.; Gonzalez, F.J.; Schuetz, E.G.; Kim, R.B. The orphan nuclear receptor HNF4alpha determines PXR- and CAR-mediated xenobiotic induction of CYP3A4. Nat. Med., 2003, 9(2), 220-224.
19. Wiwi, C.A.; Gupte, M.; Waxman, D.J. Sexually dimorphic P450 gene expression in liver-specific hepatocyte nuclear factor 4alpha-deficient mice. Mol. Endocrinol., 2004, 18(8), 1975-1987. (Pubitemid 39006502)
20. Ibeanu, G.C.; Goldstein, J.A. Transcriptional regulation of human CYP2C genes: functional comparison of CYP2C9 and CYP2C18 promoter regions. Biochemistry, 1995, 34(25), 8028-8036.
21. Kawashima, S.; Kobayashi, K.; Takama, K.; Higuchi, T.; Furihata, T.; Hosokawa, M.; Chiba, K. Involvement of hepatocyte nuclear factor 4alpha in the different expression level between CYP2C9 and CYP2C19 in the human liver. Drug Metab. Dispos., 2006, 34(6), 1012-1018. (Pubitemid 43763759)
22. Gerbal-Chaloin, S.; Daujat, M.; Pascussi, J.M.; Pichard-Garcia, L.; Vilarem, M.J.; Maurel, P. Transcriptional regulation of CYP2C9 gene. Role of glucocorticoid receptor and constitutive androstane receptor. J. Biol. Chem., 2002, 277(1), 209-217. (Pubitemid 34952047)
23. Pavek, P.; Cerveny, L.; Svecova, L.; Brysch, M.; Libra, A.; Vrzal, R.; Nachtigal, P.; Staud, F.; Ulrichova, J.; Fendrich, Z.; Dvorak, Z. Examination of Glucocorticoid receptor alpha-mediated transcriptional regulation of P-glycoprotein, CYP3A4, and CYP2C9 genes in placental trophoblast cell lines. Placenta, 2007, 28(10), 1004-1011. (Pubitemid 47355238)
24. Martinez-Jimenez, C.P.; Castell, J.V.; Gomez-Lechon, M.J.; Jover, R. Transcriptional activation of CYP2C9, CYP1A1, and CYP1A2 by hepatocyte nuclear factor 4alpha requires coactivators peroxisomal proliferator activated receptor-gamma coactivator 1alpha and steroid receptor coactivator 1. Mol. Pharmacol., 2006, 70(5), 1681-1692.
25. Surapureddi, S.; Rana, R.; Reddy, J.K.; Goldstein, J.A. Nuclear receptor coactivator 6 mediates the synergistic activation of human cytochrome P-450 2C9 by the constitutive androstane receptor and hepatic nuclear factor-4alpha. Mol. Pharmacol., 2008, 74(3), 913-923.
26. Ferguson, S.S.; Chen, Y.; LeCluyse, E.L.; Negishi, M.; Goldstein, J.A. Human CYP2C8 is transcriptionally regulated by the nuclear receptors constitutive androstane receptor, pregnane X receptor, glucocorticoid receptor, and hepatic nuclear factor 4alpha. Mol. Pharmacol., 2005, 68(3), 747-757. (Pubitemid 41206028)
27. Legraverend, C.; Eguchi, H.; Strom, A.; Lahuna, O.; Mode, A.; Tollet, P.; Westin, S.; Gustafsson, J.A. Transactivation of the rat CYP2C13 gene promoter involves HNF-1, HNF-3, and members of the orphan receptor subfamily. Biochemistry, 1994, 33(33), 9889-9897.
28. Strom, A.; Westin, S.; Eguchi, H.; Gustafsson, J.A.; Mode, A. Characterization of orphan nuclear receptor binding elements in sex-differentiated members of the CYP2C gene family expressed in rat liver. J. Biol. Chem., 1995, 270(19), 11276-11281.
29. Roussel, F.; Marie, S.; Cresteil, T. Gene structure and promoter analysis of the rat constitutive CYP2C23 gene. DNA Cell Biol., 1995, 14(9), 777-788.
30. Lehmann, J.M.; McKee, D.D.; Watson, M.A.; Willson, T.M.; Moore, J.T.; Kliewer, S.A. The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J. Clin. Invest., 1998, 102(5), 1016-1023.
31. Goodwin, B.; Hodgson, E.; D'Costa, D.J.; Robertson, G.R.; Liddle, C. Transcriptional regulation of the human CYP3A4 gene by the constitutive androstane receptor. Mol. Pharmacol., 2002, 62(2), 359-365. (Pubitemid 34804117)
32. Goodwin, B.; Hodgson, E.; Liddle, C. The orphan human pregnane X receptor mediates the transcriptional activation of CYP3A4 by rifampicin through a distal enhancer module. Mol. Pharmacol., 1999, 56(6), 1329-1339.
33. Toriyabe, T.; Nagata, K.; Takada, T.; Aratsu, Y.; Matsubara, T.; Yoshinari, K.; Yamazoe, Y. Unveiling a New Essential Cis Element for the Transactivation of the CYP3A4 Gene by Xenobiotics. Mol. Pharmacol., 2009, 75(3), 677-684.
34. Liu, F.J.; Song, X.; Yang, D.; Deng, R.; Yan, B. The far and distal enhancers in the CYP3A4 gene co-ordinate the proximal promoter in responding similarly to the pregnane X receptor but differentially to hepatocyte nuclear factor-4alpha. Biochem. J., 2008, 409(1), 243-250.
35. Tegude, H.; Schnabel, A.; Zanger, U.M.; Klein, K.; Eichelbaum, M.; Burk, O. Molecular mechanism of basal CYP3A4 regulation by hepatocyte nuclear factor 4alpha: evidence for direct regulation in the intestine. Drug Metab. Dispos., 2007, 35(6), 946-954. (Pubitemid 46804658)
36. Matsumura, K.; Saito, T.; Takahashi, Y.; Ozeki, T.; Kiyotani, K.; Fujieda, M.; Yamazaki, H.; Kunitoh, H.; Kamataki, T. Identification of a novel polymorphic enhancer of the human CYP3A4 gene. Mol. Pharmacol., 2004, 65(2), 326-334. (Pubitemid 38134260)
37. Miyata, M.; Nagata, K.; Yamazoe, Y.; Kato, R. Transcriptional elements directing a liver-specific expression of P450/6 beta A (CYP3A2) gene-encoding testosterone 6 beta-hydroxylase. Arch. Biochem. Biophys., 1995, 318(1), 71-79.
38. Ogino, M.; Nagata, K.; Miyata, M.; Yamazoe, Y. Hepatocyte nuclear factor 4-mediated activation of rat CYP3A1 gene and its modes of modulation by apolipoprotein AI regulatory protein I and v-ErbA-related protein 3. Arch. Biochem. Biophys., 1999, 362(1), 32-37. (Pubitemid 29391648)
39. Huss, J.M.; Kasper, C.B. Nuclear receptor involvement in the regulation of rat cytochrome P450 3A23 expression. J. Biol. Chem., 1998, 273(26), 16155-16162. (Pubitemid 28311387)
40. Huss, J.M.; Kasper, C.B. Two-stage glucocorticoid induction of CYP3A23 through both the glucocorticoid and pregnane X receptors. Mol. Pharmacol., 2000, 58(1), 48-57.
41. Nakayama, K.; Sudo, Y.; Sasaki, Y.; Iwata, H.; Takahashi, M.; Kamataki, T. Studies on transcriptional regulation of Cyp3a16 gene in mouse livers by application of direct DNA injection method. Biochem. Biophys. Res. Commun., 2001, 287(4), 820-824. (Pubitemid 32958542)
42. Wauthier, V.; Verbeeck, R.K.; Calderon, P.B. Decreased CYP3A2 expression and activity in senescent male Wistar rats: is there a role for HNF4alpha? Exp. Gerontol., 2006, 41(9), 846-854. (Pubitemid 44574464)
43. Sueyoshi, T.; Kawamoto, T.; Zelko, I.; Honkakoski, P.; Negishi, M. The repressed nuclear receptor CAR responds to phenobarbital in activating the human CYP2B6 gene. J. Biol. Chem., 1999, 274(10), 6043-6046. (Pubitemid 29111006)
44. Wang, H.; Faucette, S.; Sueyoshi, T.; Moore, R.; Ferguson, S.; Negishi, M.; LeCluyse, E.L. A novel distal enhancer module regulated by pregnane X receptor/constitutive androstane receptor is essential for the maximal induction of CYP2B6 gene expression. J. Biol. Chem., 2003, 278(16), 14146-14152.
45. Swales, K.; Kakizaki, S.; Yamamoto, Y.; Inoue, K.; Kobayashi, K.; Negishi, M. Novel CAR-mediated mechanism for synergistic activation of two distinct elements within the human cytochrome P450 2B6 gene in HepG2 cells. J. Biol. Chem., 2005, 280(5), 3458-3466. (Pubitemid 40223810)
46. Ding, X.; Lichti, K.; Kim, I.; Gonzalez, F.J.; Staudinger, J.L. Regulation of constitutive androstane receptor and its target genes by fasting, cAMP, hepatocyte nuclear factor alpha, and the coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha. J. Biol. Chem., 2006, 281(36), 26540-26551.
47. Min, G. Effects of TK promotor and hepatocyte nuclear factor-4 in CAR-mediated transcriptional activity of phenobarbital responsive unit of CYP2B gene in monkey kidney epithelial-derived cell line COS-7. Ann. N. Y. Acad. Sci., 2006, 1091, 258-269. (Pubitemid 47092242)
48. Beaudet, M.J.; Desrochers, M.; Lachaud, A.A.; Anderson, A. The CYP2B2 phenobarbital response unit contains binding sites for hepatocyte nuclear factor 4, PBX-PREP1, the thyroid hormone receptor beta and the liver X receptor. Biochem. J., 2005, 388(Pt 2), 407-418. (Pubitemid 40839917)
49. Pitarque, M.; Rodriguez-Antona, C.; Oscarson, M.; Ingelman-Sundberg, M. Transcriptional regulation of the human CYP2A6 gene. J. Pharmacol. Exp. Ther., 2005, 313(2), 814-822. (Pubitemid 40604183)
50. Itoh, M.; Nakajima, M.; Higashi, E.; Yoshida, R.; Nagata, K.; Yamazoe, Y.; Yokoi, T. Induction of human CYP2A6 is mediated by the pregnane X receptor with peroxisome proliferator-activated receptor-gamma coactivator 1alpha. J. Pharmacol. Exp. Ther., 2006, 319(2), 693-702.
51. Onica, T.; Nichols, K.; Larin, M.; Ng, L.; Maslen, A.; Dvorak, Z.; Pascussi, J.M.; Vilarem, M.J.; Maurel, P.; Kirby, G.M. Dexamethasone- mediated up-regulation of human CYP2A6 involves the glucocorticoid receptor and increased binding of hepatic nuclear factor 4 alpha to the proximal promoter. Mol. Pharmacol., 2008, 73(2), 451-460.
52. Yokomori, N.; Nishio, K.; Aida, K.; Negishi, M. Transcriptional regulation by HNF-4 of the steroid 15alpha-hydroxylase P450 (Cyp2a-4) gene in mouse liver. J. Steroid Biochem. Mol. Biol., 1997, 62(4), 307-314. (Pubitemid 27504761)
53. Ulvila, J.; Arpiainen, S.; Pelkonen, O.; Aida, K.; Sueyoshi, T.; Negishi, M.; Hakkola, J. Regulation of Cyp2a5 transcription in mouse primary hepatocytes: roles of hepatocyte nuclear factor 4 and nuclear factor I. Biochem. J., 2004, 381(Pt 3), 887-894. (Pubitemid 39120500)
54. Arpiainen, S.; Jarvenpaa, S.M.; Manninen, A.; Viitala, P.; Lang, M.A.; Pelkonen, O.; Hakkola, J. Coactivator PGC-1alpha regulates the fasting inducible xenobiotic-metabolizing enzyme CYP2A5 in mouse primary hepatocytes. Toxicol. Appl. Pharmacol., 2008, 232(1), 135-141.
55. Cairns, W.; Smith, C.A.; McLaren, A.W.; Wolf, C.R. Characterization of the human cytochrome P4502D6 promoter. A potential role for antagonistic interactions between members of the nuclear receptor family. J. Biol. Chem., 1996, 271(41), 25269-25276.
56. Hara, H.; Adachi, T. Contribution of hepatocyte nuclear factor-4 to down-regulation of CYP2D6 gene expression by nitric oxide. Mol. Pharmacol., 2002, 61(1), 194-200. (Pubitemid 34049527)
57. Corchero, J.; Granvil, C.P.; Akiyama, T.E.; Hayhurst, G.P.; Pimprale, S.; Feigenbaum, L.; Idle, J.R.; Gonzalez, F.J. The CYP2D6 humanized mouse: effect of the human CYP2D6 transgene and HNF4alpha on the disposition of debrisoquine in the mouse. Mol. Pharmacol., 2001, 60(6), 1260-1267.
58. Lee, S.S.; Cha, E.Y.; Jung, H.J.; Shon, J.H.; Kim, E.Y.; Yeo, C.W.; Shin, J.G. Genetic polymorphism of hepatocyte nuclear factor- 4alpha influences human cytochrome P450 2D6 activity. Hepatology, 2008, 48(2), 635-645.
59. Kuehl, P.; Zhang, J.; Lin, Y.; Lamba, J.; Assem, M.; Schuetz, J.; Watkins, P.B.; Daly, A.; Wrighton, S.A.; Hall, S.D.; Maurel, P.; Relling, M.; Brimer, C.; Yasuda, K.; Venkataramanan, R.; Strom, S.; Thummel, K.; Boguski, M.S.; Schuetz, E. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat. Genet., 2001, 27(4), 383-391. (Pubitemid 32268418)
60. Burk, O.; Tegude, H.; Koch, I.; Hustert, E.; Wolbold, R.; Glaeser, H.; Klein, K.; Fromm, M.F.; Nuessler, A.K.; Neuhaus, P.; Zanger, U.M.; Eichelbaum, M.; Wojnowski, L. Molecular mechanisms of polymorphic CYP3A7 expression in adult human liver and intestine. J. Biol. Chem., 2002, 277(27), 24280-24288. (Pubitemid 34951946)
61. Wortham, M.; Czerwinski, M.; He, L.; Parkinson, A.; Wan, Y.J. Expression of constitutive androstane receptor, hepatic nuclear factor 4 alpha, and P450 oxidoreductase genes determines interindividual variability in basal expression and activity of a broad scope of xenobiotic metabolism genes in the human liver. Drug Metab. Dispos., 2007, 35(9), 1700-1710.
62. Vyhlidal, C.A.; Gaedigk, R.; Leeder, J.S. Nuclear receptor expression in fetal and pediatric liver: correlation with CYP3A expression. Drug Metab. Dispos., 2006, 34(1), 131-137.
63. Bertolotti, M.; Gabbi, C.; Anzivino, C.; Crestani, M.; Mitro, N.; Del Puppo, M.; Godio, C.; De Fabiani, E.; Macchioni, D.; Carulli, L.; Rossi, A.; Ricchi, M.; Loria, P.; Carulli, N. Age-related changes in bile acid synthesis and hepatic nuclear receptor expression. Eur. J. Clin. Invest., 2007, 37(6), 501-508. (Pubitemid 46817345)
64. Wiwi, C.A.; Waxman, D.J. Role of hepatocyte nuclear factors in growth hormone-regulated, sexually dimorphic expression of liver cytochromes P450. Growth Factors, 2004, 22(2), 79-88.
65. Davey, H.W.; Wilkins, R.J.; Waxman, D.J. STAT5 signaling in sexually dimorphic gene expression and growth patterns. Am. J. Hum. Genet., 1999, 65(4), 959-965.
66. Sasaki, Y.; Takahashi, Y.; Nakayama, K.; Kamataki, T. Cooperative regulation of CYP2C12 gene expression by STAT5 and liver-specific factors in female rats. J. Biol. Chem., 1999, 274(52), 37117-37124. (Pubitemid 30016786)
67. Holloway, M.G.; Laz, E.V.; Waxman, D.J. Codependence of growth hormone-responsive, sexually dimorphic hepatic gene expression on signal transducer and activator of transcription 5b and hepatic nuclear factor 4alpha. Mol. Endocrinol., 2006, 20(3), 647-660.
68. Thangavel, C.; Shapiro, B.H. Inherent sexually dimorphic expression of hepatic CYP2C12 correlated with repressed activation of growth hormone-regulated signal transduction in male rats. Drug Metab. Dispos., 2008, 36(9), 1884-1895.
69. Wiwi, C.A.; Waxman, D.J. Role of hepatocyte nuclear factors in transcriptional regulation of male-specific CYP2A2. J. Biol. Chem., 2005, 280(5), 3259-3268.
70. Laz, E.V.; Holloway, M.G.; Chen, C.S.; Waxman, D.J. Characterization of three growth hormone-responsive transcription factors preferentially expressed in adult female liver. Endocrinology, 2007, 148(7), 3327-3337.
71. Jover, R.; Bort, R.; Gomez-Lechon, M.J.; Castell, J.V. Downregulation of human CYP3A4 by the inflammatory signal interleukin-6: molecular mechanism and transcription factors involved. FASEB J., 2002, 16(13), 1799-1801.
72. Park, J.I.; Tsai, S.Y.; Tsai, M.J. Molecular mechanism of chicken ovalbumin upstream promoter-transcription factor (COUP-TF) actions. Keio J. Med., 2003, 52(3), 174-181.
73. Kamiya, A.; Inoue, Y.; Gonzalez, F.J. Role of the hepatocyte nuclear factor 4alpha in control of the pregnane X receptor during fetal liver development. Hepatology, 2003, 37(6), 1375-1384.
74. Bhalla, S.; Ozalp, C.; Fang, S.; Xiang, L.; Kemper, J.K. Ligand-activated pregnane X receptor interferes with HNF-4 signaling by targeting a common coactivator PGC-1alpha. Functional implications in hepatic cholesterol and glucose metabolism. J. Biol. Chem., 2004, 279(43), 45139-45147.
75. Pascual, M.; Gomez-Lechon, M.J.; Castell, J.V.; Jover, R. ATF5 is a highly abundant liver-enriched transcription factor that cooperates with constitutive androstane receptor in the transactivation of CYP2B6: implications in hepatic stress responses. Drug Metab. Dispos., 2008, 36(6), 1063-1072. (Pubitemid 351717463)
76. Staudinger, J.L.; Goodwin, B.; Jones, S.A.; Hawkins-Brown, D.; MacKenzie, K.I.; LaTour, A.; Liu, Y.; Klaassen, C.D.; Brown, K.K.; Reinhard, J.; Willson, T.M.; Koller, B.H.; Kliewer, S.A. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc. Natl. Acad. Sci. USA, 2001, 98(6), 3369-3374.
77. Ourlin, J.C.; Lasserre, F.; Pineau, T.; Fabre, J.M.; Sa-Cunha, A.; Maurel, P.; Vilarem, M.J.; Pascussi, J.M. The small heterodimer partner interacts with the pregnane X receptor and represses its transcriptional activity. Mol. Endocrinol., 2003, 17(9), 1693-1703.
78. Miao, J.; Fang, S.; Bae, Y.; Kemper, J.K. Functional inhibitory cross-talk between constitutive androstane receptor and hepatic nuclear factor-4 in hepatic lipid/glucose metabolism is mediated by competition for binding to the DR1 motif and to the common coactivators, GRIP-1 and PGC-1alpha. J. Biol. Chem., 2006, 281(21), 14537-14546.
79. Ueda, A.; Hamadeh, H.K.; Webb, H.K.; Yamamoto, Y.; Sueyoshi, T.; Afshari, C.A.; Lehmann, J.M.; Negishi, M. Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital. Mol. Pharmacol., 2002, 61(1), 1-6. (Pubitemid 34049505)
80. Yoon, J.C.; Puigserver, P.; Chen, G.; Donovan, J.; Wu, Z.; Rhee, J.; Adelmant, G.; Stafford, J.; Kahn, C.R.; Granner, D.K.; Newgard, C.B.; Spiegelman, B.M. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature, 2001, 413(6852), 131-138. (Pubitemid 32867868)
81. Sidhu, J.S.; Omiecinski, C.J. Insulin-mediated modulation of cytochrome P450 gene induction profiles in primary rat hepatocyte cultures. J. Biochem. Mol. Toxicol., 1999, 13(1), 1-9.
82. Tamaki, H.; Sakuma, T.; Uchida, Y.; Jaruchotikamol, A.; Nemoto, N. Activation of CYP1A1 gene expression during primary culture of mouse hepatocytes. Toxicology, 2005, 216(2-3), 224-231. (Pubitemid 41712011)
83. Donato, M.T.; Lahoz, A.; Jimenez, N.; Perez, G.; Serralta, A.; Mir, J.; Castell, J.V.; Gomez-Lechon, M.J. Potential impact of steatosis on cytochrome P450 enzymes of human hepatocytes isolated from fatty liver grafts. Drug Metab. Dispos., 2006, 34(9), 1556-1562.
84. Sugatani, J.; Wada, T.; Osabe, M.; Yamakawa, K.; Yoshinari, K.; Miwa, M. Dietary inulin alleviates hepatic steatosis and xenobiotics-induced liver injury in rats fed a high-fat and high-sucrose diet: association with the suppression of hepatic cytochrome P450 and hepatocyte nuclear factor 4alpha expression. Drug Metab. Dispos., 2006, 34(10), 1677-1687. (Pubitemid 44427470)
85. Vossen, C.; Erard, M. Down-regulation of nuclear receptor DNAbinding activity by nitric oxide-HNF4 as a model system. Med. Sci. Monit., 2002, 8(10), RA217-220. (Pubitemid 35257342)