Constitutive androstane receptor and pregnane X receptor gene expression in human liver: Interindividual variability and correlation with CYP2B6 mRNA levels

Drug Metabolism and Disposition

Volumn 31, Issue 1, 2003, Pages 7-10

  Chang, Thomas K H ^a   Bandiera, Stelvio M ^a   Chen, Jie ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROSTANE RECEPTOR; CYTOCHROME P450 2B6; HORMONE RECEPTOR; LIVER ENZYME; MESSENGER RNA; PREGNANE X RECEPTOR; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

ARTICLE; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; GENETIC VARIABILITY; HUMAN; HUMAN TISSUE; LIVER; NUCLEOTIDE SEQUENCE; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; RECEPTOR GENE;

ARYL HYDROCARBON HYDROXYLASES; GENE EXPRESSION REGULATION; HUMANS; LIVER; OXIDOREDUCTASES, N-DEMETHYLATING; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, STEROID; RNA, MESSENGER; TRANSCRIPTION FACTORS; VARIATION (GENETICS);

MAMMALIA;

EID: 0038128342     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: 10.1124/dmd.31.1.7     Document Type: Article

References (29)

1. Aranda A and Pascual A (2001) Nuclear hormone receptors and gene expression. Physiol Rev 81:129-130.
2. Baes M, Gulick T, Choi HS, Martinoli MG, Simha D, and Moore DD (1994) A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements. Mol Cell Biol 14:1544-1552.
3. Beigneux AP, Moser AH, Shigenaga JK, Grunfeld C, and Feingold KR (2002) Reduction in cytochrome P-450 enzyme expression is associated with repression of CAR (constitutive androstane receptor) and PXR (pregnane X receptor) in mouse liver during the acute phase response. Biochem Biophys Res Commun 293:145-149.
4. Bertilsson G, Heidrich J, Svensson K, Asman M, Jendeberg L, Sydow-Backman M, Ohlsson R, Postlind H, Blomquist P, and Berkenstam A (1998) Identification of a human nuclear receptor defines a new signalling pathway for CYP3A induction. Proc Natl Acad Sci USA 95:12208-12213.
5. Blumberg B, Sabbagh W Jr, Juguilon H, Bolado J Jr, van Meter CM, Ong ES, and Evans RM (1998) SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Dev 12:3195-3205.
6. Chang TKH, Chen J, Pillay V, Ho JY, and Bandiera SM (2003) Real-time polymerase chain reaction analysis of CYP1B1 gene expression in human liver. Toxicol Sci, in press.
7. Chang TKH, Weber GF, Crespi CL, and Waxman DJ (1993) Differential activation of cyclo-phosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes. Cancer Res 53:5629-5637.
8. Chang TKH, Yu L, Maurel P, and Waxman DJ (1997) Enhanced cyclophosphamide and ifosfamide activation in primary human hepatocyte cultures: response to cytochrome P-450 inducers and autoinduction by oxazaphosphorines. Cancer Res 57:1946-1954.
9. Choi HS, Chung M, Tzameli I, Simha D, Lee YK, Seol W, and Moore DD (1997) Differential transactivation by two isoforms of the orphan nuclear hormone receptor CAR. J Biol Chem 272:23565-23571.
10. Code EL, Crespi CL, Penman BW, Gonzalez FJ, Chang TKH, and Waxman DJ (1997) Human cytochrome P450 2B6. Interindividual hepatic expression, substrate specificity and role in procarcinogen activation. Drug Metab Dispos 25:985-993.
11. Dehal SS and Kupfer D (1994) Metabolism of the proestrogenic pesticide methoxychlor by hepatic P450 monooxygenases in rat and humans. Dual pathways involving novel ortho ring-hydroxylation by CYP2B. Drug Metab Dispos 22:937-946.
12. Dotzlaw H, Leygue E, Watson P, and Murphy LC (1999) The human orphan receptor PXR messenger RNA is expressed in both normal and neoplastic breast tissue. Clin Cancer Res 5:2103-2107.
13. Ekins S, VandenBranden M, Ring BJ, Gillespie JS, Yang TJ, Gelboin HV, and Wrighton SA (1998) Further characterization of the expression in liver and catalytic activity of CYP2B6. J Phamacol Exp Ther 286:1253-1259.
14. Ekins S, VandenBranden M, Ring BJ, and Wrighton SA (1997) Examination of purported probes of human CYP2B6. Pharmacogenetics 7:165-179.
15. Ekins S and Wrighton SA (1999) The role of CYP2B6 in human xenobiotic metabolism. Drug Metab Rev 31:719-754.
16. Goodwin B, Moore LB, Stoltz CM, McKee DD, and Kliewer SA (2001) Regulation of the human CYP2B6 gene by the nuclear pregnane X receptor. Mol Pharmacol 60:427-431.
17. Goodwin B, Redinbo MR, and Kliewer SA (2002) Regulation of CYP3A gene transcription by the pregnane X receptor. Annu Rev Pharmacol Toxicol 42:1-23.
18. Kliewer SA, Moore JT, Wade L, Staudinger JL, Watson MA, Jones SA, McKee DD, Oliver BB, Willson TM, Zetterstrom RH, et al. (1998) An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 92:73-82.
19. Lang T, Klein K, Fischer J, Nussler AK, Neuhaus P, Hofmann U, Eichelbaum M, Schwab M, and Zanger UM (2001) Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics 11:399-415.
20. Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, and Kliewer SA (1998) The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest 102:1016-1023.
21. Pascussi JM, Drocourt L, Fabre JM, Maurel P, and Vilarem MJ (2000a) Dexamethasone induces pregnane X receptor and retinoid X receptor-α expression in human hepatocytes: Synergistic increase of CYP3A4 induction by pregnane X receptor activators. Mol Pharmacol 58:361-372.
22. Pascussi JM, Drocourt L, Gerbal-Chaloin S, Fabre JM, Maurel P, and Vilarem MJ (2001) Dual effect of dexamethasone on CYP3A4 gene expression in human hepatocytes. Sequential role of glucocorticoid receptor and pregnane X receptor. Eur J Biochem 268:6346-6357.
23. Pascussi JM, Gerbal-Chaloin S, Fabre JM, Maurel P, and Vilarem MJ (2000b) Dexamethasone enhances constitutive androstane receptor expression in human hepatocytes: consequences on cytochrome P450 gene regulation. Mol Pharmacol 58:1441-1450.
24. Pascussi JM, Gerbal-Chaloin S, Pichard-Garcia L, Daujat M, Fabre JM, Maurel P, and Vilarem MJ (2000c) Interleukin-6 negatively regulates the expression of pregnane X receptor and constitutively activated receptor in primary human hepatocytes. Biochem Biophys Res Commun 274:707-713.
25. Rodriguez-Antona C, Donato MT, Pareja E, Gomez-Lechon MJ, and Castell JV (2001) Cytochrome P-450 mRNA expression in human liver and its relationship with enzyme activity. Arch Biochem Biophys 393:308-315.
26. Sueyoshi T and Negishi M (2001) Phenobarbital response elements of cytochrome P450 genes and nuclear receptors. Annu Rev Pharmacol Toxicol 41:123-143.
27. Yamano S, Nhamburo PT, Aoyama T, Meyer UA, Inaba T, Kalow W, Gelboin HV, McBride WO, and Gonzalez FJ (1989) cDNA cloning and sequence and cDNA-directed expression of human P450 IIB1: identification of a normal and two variant cDNAs derived from the CYP2B locus on chromosome 19 and differential expression of the IIB mRNAs in human liver. Biochemistry 28:7340-7348.
28. Yang TJ, Krausz KW, Shou M, Yang SK, Buters JTM, Gonzalez FJ, and Gelboin HV (1998) Inhibitory monoclonal antibody to human cytochrome P450 2B6. Biochem Pharmacol 55:1633-1640.
29. Zhang J, Kuehl P, Green ED, Touchman JW, Watkins PB, Daly A, Hall SD, Maurel P, Relling M, Brimer C, et al. (2001) The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants. Pharmacogenetics 11:555-572.