Phenobarbital-induced expression of cytochrome P450 genes

• Autorzy: Czekaj P.
• Języki publikacji: EN

Abstrakty

EN

In contrast to the well-known Ah receptor-mediated regulation of the CYP1A1 gene by polycyclic aromatic hydrocarbons, the molecular mechanism by which phenobarbital (PB) and PB-like inducers affect transcription of CYP genes remains unknown; no receptor for these chemicals has been found to date. However, in the last 5 years PB-responsive sequences have been identified in the 5' flanking regions of several P450 genes. The phenobarbital-responsive enhancer unit (PBRU) of CYP2B gene family members contain two potential nuclear receptor binding sites (NR1 and NR2) that flank a nuclear factor 1 (NF-1) binding motif. The nuclear factors that regulate PBRU activity have not yet been characterized. It seems that PB may activate multiple nuclear orphan receptors to induce various CYP genes. CYP2B and CYP3A genes appear to be targets for the orphan receptors CAR and PXR, respectively. It is also possible that the pleiotropic effects of PB can, in part, be explained by the ability of the CAR-RXR heterodimer to bind to a variety of nuclear receptor binding motifs. The induction of cytochromes P450 may result in interactions between xenobiotics and in the interference of xenobiotic metabolism and endogenous signalling pathways.

Słowa kluczowe

EN

pregnane X receptor; constitutively activated receptor; gene; CYP2B gene; orphan receptor; CYP1A1 gene; reactive oxygen species; cytochrome P450; CYP3A gene; CYP gene

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2000
• Tom: 47
• Numer: 4
• Opis fizyczny: p.1093-1105,fig.,ref.

Twórcy

autor

Czekaj P.

• Silesian Medical Academy, Medykow 18, 40-752 Katowice, Poland

Bibliografia

• 1. Nelson, D., Koymans, L., Kamataki, T., Stegeman, J., Feyereisen, R., Waxman, D., Waterman, M., Gotoh, O., Coon, M., Esta- brook, R., Gunsalus, I. & Nebert, D. (1996) P450 superfamily: Update on new sequences, gene mapping, accession numbers and nomen­clature. Pharmacogenetics 6, 1-42.
• 2. Denison, M. & Whitlock, J. (1995) Xenobiotic- inducible transcription of cytochrome P450 genes. J. Biol. Chem. 270, 18175-18178.
• 3. Guengerich, F. (1995) Human cytochrome P450 enzymes; in Cytochrome P450: Structure, Mechanisms and Biochemistry (Ortiz de Montellano, P., ed.) pp. 473-575, Plenum Press, New York.
• 4. Bartsch, H., Castegnaro, M., Rojas, M., Camus, A.-M., Alexandrov, K. & Lang, M. (1992) Expression of pulmonary cytochrome P4501A1 and carcinogen DNA adduct forma­tion in high risk subjects for tobacco-related lung cancer. Toxicol. Lett. 64/65, 477-483.
• 5. Kato, S., Bowman, E., Harrington, A., Blomeke, B. & Shields, P. (1995) Human lung carcinogen-DNA adduct levels mediated by ge­netic polymorphisms in vivo. J. Natl. Cancer Inst. 87, 902-907.
• 6. Aust, S., Chignell, C., Bray, T., Kalyanaraman, B. & Mason, R. (1993) Contemporary issues in toxicology. Free radicals in toxicology. Toxicol. Appl. Pharmacol. 120, 168-178.
• 7. Dizdaroglu, M. (1998) Mechanisms of free rad­ical damage to DNA; in DNA and Free Radi­cals: Techniques, Mechanisms and Applications (Aruoma, O. & Halliwell, B., eds.) pp. 3-26, OICA Int. Saint Lucia, London.
• 8. Villard, P.-H., Seree, E., Re, J.-L., De Meo, M., Barra, Y., Attolini, L., Dumenil, G., Catalin, J., Durand, A. & Lacarelle, B. (1998) Effects of to­bacco smoke on the gene expression of the Cyp1a, Cyp2b, Cyp2e, and Cyp3a subfamilies in mouse liver and lung: Relation to single strand breaks of DNA. Toxicol. Appl. Phar­macol. 148, 195-204.
• 9. Czekaj, P. & Nowaczyk-Dura, G. (1996) Effects of different synthetic steroid combinations on the activity of mixed function oxidase system and on the morphology of rat liver. Exp. Toxic. Pathol. 48 (Suppl. II) 82-87.
• 10. Czekaj, P. & Nowaczyk-Dura, G. (1999) In­hibiting effect of ethinylestradiol/levonorge- strel combination on microsomal enzymatic activities in rat liver and kidney. Eur. J. Drug Metab. Pharmacokinet. 24, 243-248.
• 11. Czekaj, P., Wiaderkiewicz, A. & Wiader- kiewicz, R. (2000) Immunodetection of cyto- chrome P450 isoforms in fetus and adult fe­male Wistar rats. Acta Pol. Toxicol. 1,17-31.
• 12. Chien, J., Thummel, K. & Slattery, J. (1997) Pharmacokinetic consequences of induction of CYP2E1 by ligand stabilization. Drug Metab. Dispos. 25, 1165-1175.
• 13. Whitlock, J. & Denison, M. (1995) Human cytochrome P450 enzymes; in Cytochrome P450: Structure, Mechanisms and Biochemistry (Ortiz de Montellano, P., ed.) pp. 367-390, Ple­num Press, New York.
• 14. Brockmoller, J., Cascorbi, I., Kerb, R., Sachse, C. & Roots, I. (1998) Polymorphisms in xeno- biotic conjugation and disease predisposition. Toxicol. Lett. 102-103,173-183.
• 15. Waxman, D. & Azaroff, L. (1992) Phenobarbi­tal induction of cytochrome P-450 gene expres­sion. Biochem. J. 281, 577-592.
• 16. Frueh, F., Zanger, U. & Meyer, U. (1997) Ex­tent and character of phenobarbital-mediated changes in gene expression in the liver. Mol. Pharmacol. 51, 363-369.
• 17. Smith, G., Henderson, C., Parker, M., White, R., Bars, R. & Wolf, R. (1993) 1,4-Bis[2-(3,5-di- chloropyridyloxy)]benzene, an extremely po­tent modulator of mouse hepatic cytochrome P-450 gene expression. Biochem. J. 289, 807­813.
• 18. Honkakoski, P., Moore, R., Washburn, K. & Negishi, M. (1998) Activation by diverse xeno- chemicals of the 51-base pair phenobarbi- tal-responsive enhancer module in the Cyp2b10 gene. Mol. Pharmacol. 53, 597-601.
• 19. Chang, T., Yu, L., Maurel, P. & Waxman, D. (1997) Enhanced cyclophosphamide and ifosfamide activation in primary human hepa- tocyte cultures: Response to cytochrome P-450 inducers and autoinduction by oxazaphos- phorines. Cancer Res. 57, 1946-1954.
• 20. Anderson, G. (1998) A mechanistic approach to antiepileptic drug interactions. Ann. Pharmacother. 32, 554-563.
• 21. Dogra, S., Whitelaw, M. & May, B. (1997) Transcriptional activation of cytochrome P450 genes by different classes of chemical in- ducers. Clin. Exp. Pharmacol. Physiol. 25,1-9.
• 22. Shaw, P., Adesnik, M., Weiss, M. & Corcos, L. (1993) The phenobarbital-induced transcrip­tional activation of cytochrome P-450 genes is blocked by the glucocorticoid-progesterone an­tagonist RU486. Mol. Pharmacol. 44, 775­783.
• 23. Pinkus, R., Bergelson, S. & Daniel, V. (1993) Phenobarbital induction of AP-1 binding activ­ity mediates activation of glutathione S-trans- ferase and quinone reductase gene expres­sion. Biochem. J. 290, 637-640.
• 24. Fulco, A. (1991) P450BM-3 and other inducible bacterial P450 cytochromes: Biochemistry and regulation. Annu. Rev. Pharmacol. Toxi­col. 31, 177-203.
• 25. Shaw, G. & Fulco, A. (1992) Barbiturate-medi­ated regulation of expression of the cyto­chrome P-450BM-3 gene of Bacillus mega- terium by Bm3R1 protein. J. Biol. Chem. 267, 5515-5526.
• 26. Shaw, G. & Fulco, A. (1993) Inhibition by bar­biturates of the binding of Bm3R1 repressor to its operator site on the barbiturate-in- ducible cytochrome P450bm-3 gene of Bacillus megaterium. J. Biol. Chem. 268, 2997-3004.
• 27. Kemper, B. (1998) Regulation of cytochrome P450 gene transcription by phenobarbital. Prog. Nucleic Acid Res. 61, 25-64.
• 28. He, J. & Fulco, A. (1991) A barbiturate-re­gulated protein binding to a common sequence in the cytochrome P450 genes of rodents and bacteria. J. Biol. Chem. 226, 7864-7869.
• 29. Rangarajan, P. & Padmanaban, G. (1989) Reg­ulation of cytochrome P-450b/e gene expres­sion by a heme- and phenobarbitone-modulat- ed transcription factor. Proc. Natl. Acad. Sci. U.S.A. 86, 3963-3967.
• 30. Ramsden, R., Sommer, K.M. & Omiecinski, C.J. (1993) Phenobarbital induction and tis­sue-specific expression of the rat CYP2B2 gene in transgenic mice. J. Biol. Chem. 268, 21722-21726.
• 31. Park, Y., Li, H. & Kemper, B. (1996) Phenobar­bital induction mediated by a distal CYP2B2 sequence in rat liver transiently transfected in situ. J. Biol. Chem. 271, 23725-23728.
• 32. Shaw, G., Sung, C., Liu, C. & Lin, C. (1998) Ev­idence against the Bm1P1 protein as a positive transcription factor for barbiturate-mediated induction of cytochrome P450bm1 in Bacillus megaterium. J. Biol. Chem. 273, 7996-8002.
• 33. Dogra, S. & May, B. (1997) Liver enriched transcription factors, HNF-1, HNF-3 and C/EBP are major contributors to the strong activity of the chicken CYP2H1 promoter in chick embryo hepatocytes. DNA Cell Biol. 16, 1407-1418.
• 34. Prabhu, L., Upadhya, P., Ram, N., Nirodi, C., Sultana, S., Vatsala, P., Mani, S., Rangarajan, P., Surolia, A. & Padmanaban, G. (1995) A model for the transcriptional regulation of the CYP2B1/B2 gene in rat liver. Proc. Natl. Acad. Sci. U.S.A. 92, 9628-9632.
• 35. Meyer, U. & Hoffmann, K. (1999) Phenobarbi- tal-mediated changes in gene expression in the liver. DrugMetab. Rev. 31, 365-373.
• 36. Park, Y. & Kemper, B. (1996) The CYP2B1 proximal promoter contains a functional C/EBP regulatory element. DNA Cell Biol. 15, 693-701.
• 37. Trottier, E., Belzil, A., Stoltz, C. & Anderson, A. (1995) Localization of a phenobarbital-res- ponsive element (PBRE) in the 5'-flanking re­gion of the rat CYP2B2 gene. Gene 158, 263-268.
• 38. Stoltz, C., Vachon, M.-H., Trottier, E., Dubois, S., Paquet, Y. & Anderson, A. (1998) The CYP2B2 phenobarbital response unit contains an accessory factor element and a putative glucocorticoid response element essential for conferring maximal phenobarbital responsive­ness. J. Biol. Chem. 273, 8528-8536.
• 39. Honkakoski, P., Zelko, I., Sueyoshi, T. & Negishi, M. (1998) The nuclear orphan recep­tor CAR-retinoid X receptor heterodimer acti­vates the phenobarbital-responsive enhancer module of the CYP2B gene. Mol. Cell. Biol. 18, 5652-5658.
• 40. Sueyoshi, T., Kawamoto, T., Zelko, I., Honka­koski, P. & Negishi, M. (1999) The repressed nuclear receptor CAR responds to phenobarbi­tal in activating the human CYP2B6 gene. J. Biol. Chem. 274, 6043-6046.
• 41. Stoltz, C. & Anderson, A. (1999) Positive regu­lation of the rat CYP2B2 phenobarbital re­sponse unit by the nuclear receptor hexamer half-site nuclear factor 1 complex. Biochem. Pharmacol. 57, 1073-1076.
• 42. Honkakoski, P. & Negishi, M. (1997) Charac­terization of a phenobarbital-responsive en­hancer module in mouse P450 Cyp2b10 gene. J. Biol. Chem. 272, 14943-14949.
• 43. Czekaj, P. (1996) Interakcje receptorów hor­monu tarczycy i pochodnych witamin A i D z DNA. Post. Biol. Kom. 23, 261-278 (in Pol­ish).
• 44. Hahn, C., Hansen, A. & May, B. (1991) Transcriptional regulation of the chicken CYP2H1 gene. J. Biol. Chem. 266, 17031­17039.
• 45. Dogra, S., Davidson, B. & May, B. (1999) Anal­ysis of a phenobarbital-responsive enhancer sequence located in the 5' flanking region of the chicken CYP2H1 gene: Identification and characterization of functional protein-binding sites. Mol. Pharmacol. 55, 14-22.
• 46. Enmrak, E. & Gustafsson, J. (1996) Orphan nuclear receptors — the first eight years. Mol. Endocrinol. 10, 1293-1307.
• 47. Baes, M., Gulick, T., Choi, H., Martinoli, M., Simha, D. & Moore, D. (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.
• 48. Forman, B., Tzameli, I., Choi, H.-S., Chen, J., Simha, D., Seol, W., Evans, R. & Moore, D. (1998) Androstane metabolites bind to and de­activate the nuclear receptor CAR-/3. Nature 395, 612-615.
• 49. Zhou, Z., Wong, C., Sar, M. & Wilson, E. (1994) The androgen receptor: An overview. Rec. Prog. Horm. Res. 49, 249-274.
• 50. Kliewer, S., Lehmann, J. & Willson, T. (1999) Orphan nuclear receptors: Shifting endocri­nology into reverse. Science 284, 757-760.
• 51. Lehmann, J., McKee, D., Watson, M., Willson, T., Moore, J. & Kliewer, S. (1998) The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene ex­pression and cause drug interactions. J. Clin. Invest. 102, 1016-102.
• 52. Hashimoto, H., Toide, K., Kitamura, R., Fujita, M., Tagawa, S., Itoh, S. & Kamataki, T. (1993) Gene structure of CYP3A4, an adult- specific form of cytochrome P450 in human livers, and its transcriptional control. Eur. J. Biochem. 218, 585-595.
• 53. Kliewer, S., Moore, J., Wade, L., Staudinger, J., Watson, M., Jones, S., McKee, D., Oliver, B., Wilson, T., Zetterström, R., Perlmann, T. & Lehmann, J. (1998) An orphan nuclear re­ceptor activated by pregnanes defines a novel steroid signaling pathway. Cell 92, 73-82.
• 54. Beato, M. (1989) Gene regulation by steroid hormones. Cell 56, 335-344.
• 55. Nebert, D. (1994) Drug-metabolizing enzymes in ligand-modulated transcription. Biochem. Pharmacol. 147, 25-27.
• 56. Kornberg, R. & Lorch, Y. (1992) Chromatin structure and transcription. Annu. Rev. Cell Biol. 8, 563-587.
• 57. Sidhu, J. & Omiecinski, C. (1995) cAMP-as­sociated inhibition of phenobarbital-inducible cytochrome P450 gene expression in primary hepatocyte cultures. J. Biol. Chem. 270, 12762-12773.