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CYP2H1  -  cytochrome P450 2H1

Gallus gallus

 
 
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Disease relevance of CYP2H1

 

High impact information on CYP2H1

  • Furthermore, CXR binds to a previously identified phenobarbital-responsive enhancer unit (PBRU) in the 5'-flanking region of the chicken CYP2H1 gene [1].
  • A conserved nuclear receptor consensus sequence (DR-4) mediates transcriptional activation of the chicken CYP2H1 gene by phenobarbital in a hepatoma cell line [3].
  • When constructs containing more than 1.1 kb of CYP2H1 gene 5'-flanking sequence were examined, phenobarbital induction of CAT expression was observed, and a drug-responsive domain between positions -5.9 and -1.1 kb was identified [4].
  • Transient transfection assays were carried out in primary cultures using constructs containing different lengths of CYP2H1 gene 5'-flanking sequence fused to the reporter chloramphenicol acetyl-transferase (CAT) gene [4].
  • To assess the reported role of protein phosphorylation in drug-mediated induction, we treated LMH cells with okadaic acid and observed increased mRNA of delta-aminolevulinate synthase and CYP2H1 whereas expression of CYP3A37 was decreased [5].
 

Chemical compound and disease context of CYP2H1

  • Squalestatin1 (SQ1), a potent inhibitor of squalene synthase produced a dose-dependent induction of cytochromes P450 CYP2H1 and CYP3A37 mRNAs in chicken hepatoma cells [6].
 

Biological context of CYP2H1

  • In previous studies, a 264-base-pair (bp) phenobarbital-responsive enhancer unit (PBRU) located at -1671 to -1408 upstream of the chicken CYP2H1 transcriptional start-site increased gene expression when activated by the chicken xenobiotic-sensing orphan nuclear receptor CXR [7].
  • 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 [8].
  • Another construct pCAT, with the first 547 bp of 5' flanking region of the CYP2H1 gene, is not responsive to drug and basal expression of this construct was not altered by the addition of 2-aminopurine [9].
 

Anatomical context of CYP2H1

  • The antiglucocorticoid RU486 inhibits phenobarbital induction of the chicken CYP2H1 gene in primary hepatocytes [10].
  • In keeping with the tissue-restricted expression of the CYP2H1 gene, gel shift experiments established that the proteins binding to these enhancer sites are enriched in chicken liver, kidney, and small intestine [8].
  • To examine the mechanism of this induction further, we determined the effects of various structurally related and unrelated inhibitors of protein synthesis on CYP2H1 expression in cultured chick embryo hepatocytes [11].
 

Associations of CYP2H1 with chemical compounds

  • Chicken xenobiotic receptor, pregnane X receptor, and constitutive androstane receptor all bound to the CYP2H1 phenobarbital-inducible enhancer units in gel-shift experiments [5].
  • In marked contrast, CYP2H1 mRNA induced by the phenobarbital-type inducers glutethimide and 2-allylisopropylacetamide is not affected by RU486 [10].
  • This proposal was supported by experiments with the histone deacetylase inhibitor, trichostatin A, which resulted in the superinduction of the drug response but had little effect on basal expression of the CYP2H1 gene [12].
  • Cycloheximide acetate required deesterification to cycloheximide for both inhibition of protein synthesis and induction of CYP2H1 mRNA [11].
  • The effects of MMC on both basal and drug-inducible ALA synthase and CYP2H1 mRNA expression were principally a result of changes in the transcription rates of these genes [13].
 

Regulatory relationships of CYP2H1

 

Other interactions of CYP2H1

  • Transient expression analysis established that the promoter activity of the CYP2H2 gene was about ninefold lower than the CYP2H1 gene [14].
  • In the present study, we report that the protein kinase inhibitor 2-aminopurine markedly inhibits the phenobarbital-induced activation of CYP2H1 and ALAS-1 genes as measured by Northern blot analysis, but does not alter the basal expression of these genes in the absence of drug [9].
  • The PCR efficiency ranged from 1.30 to 1.70, 0.86 to 1.70 and 0.91 to 1.58 for CYP3A, CYP2H1 and beta-actin, respectively in Bantam, Bantamized White Leghorn and White Leghorn chicks [15].
 

Analytical, diagnostic and therapeutic context of CYP2H1

References

  1. CXR, a chicken xenobiotic-sensing orphan nuclear receptor, is related to both mammalian pregnane X receptor (PXR) and constitutive androstane receptor (CAR). Handschin, C., Podvinec, M., Meyer, U.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  2. 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. Dogra, S.C., May, B.K. DNA Cell Biol. (1997) [Pubmed]
  3. A conserved nuclear receptor consensus sequence (DR-4) mediates transcriptional activation of the chicken CYP2H1 gene by phenobarbital in a hepatoma cell line. Handschin, C., Meyer, U.A. J. Biol. Chem. (2000) [Pubmed]
  4. Transcriptional regulation of the chicken CYP2H1 gene. Localization of a phenobarbital-responsive enhancer domain. Hahn, C.N., Hansen, A.J., May, B.K. J. Biol. Chem. (1991) [Pubmed]
  5. Conservation of signaling pathways of xenobiotic-sensing orphan nuclear receptors, chicken xenobiotic receptor, constitutive androstane receptor, and pregnane X receptor, from birds to humans. Handschin, C., Podvinec, M., Stöckli, J., Hoffmann, K., Meyer, U.A. Mol. Endocrinol. (2001) [Pubmed]
  6. A Link between cholesterol levels and phenobarbital induction of cytochromes P450. Ourlin, J.C., Handschin, C., Kaufmann, M., Meyer, U.A. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  7. Multiple enhancer units mediate drug induction of CYP2H1 by xenobiotic-sensing orphan nuclear receptor chicken xenobiotic receptor. Handschin, C., Podvinec, M., Looser, R., Amherd, R., Meyer, U.A. Mol. Pharmacol. (2001) [Pubmed]
  8. 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. Dogra, S.C., Davidson, B.P., May, B.K. Mol. Pharmacol. (1999) [Pubmed]
  9. Phenobarbital-induced activation of CYP2H1 and 5-aminolevulinate synthase genes in chick embryo hepatocytes is blocked by an inhibitor of protein phosphorylation. Dogra, S.C., May, B.K. Arch. Biochem. Biophys. (1996) [Pubmed]
  10. The antiglucocorticoid RU486 inhibits phenobarbital induction of the chicken CYP2H1 gene in primary hepatocytes. Davidson, B.P., Dogra, S.C., May, B.K. Mol. Pharmacol. (2001) [Pubmed]
  11. Inhibition of protein synthesis increases the transcription of the phenobarbital-inducible CYP2H1 and CYP2H2 genes in chick embryo hepatocytes. Hamilton, J.W., Bement, W.J., Sinclair, P.R., Sinclair, J.F., Alcedo, J.A., Wetterhahn, K.E. Arch. Biochem. Biophys. (1992) [Pubmed]
  12. Evidence that the coactivator CBP/p300 is important for phenobarbital-induced but not basal expression of the CYP2H1 gene. Dogra, S.C., Tremethick, D., May, B.K. Mol. Pharmacol. (2003) [Pubmed]
  13. Preferential effects of the chemotherapeutic DNA crosslinking agent mitomycin C on inducible gene expression in vivo. Caron, R.M., Hamilton, J.W. Environ. Mol. Mutagen. (1995) [Pubmed]
  14. A duplicated HNF-3 binding site in the CYP2H2 promoter underlies the weak phenobarbital induction response. Davidson, B.P., Dogra, S.C., May, B.K. Int. J. Biochem. Cell Biol. (2001) [Pubmed]
  15. Comparative evaluation of phenobarbital-induced CYP3A and CYP2H1 gene expression by quantitative RT-PCR in Bantam, Bantamized White Leghorn and White Leghorn chicks. Goriya, H.V., Kalia, A., Bhavsar, S.K., Joshi, C.G., Rank, D.N., Thaker, A.M. J. Vet. Sci. (2005) [Pubmed]
  16. Mechanism of the synergistic induction of CYP2H by isopentanol plus ethanol: comparison to glutethimide and relation to induction of 5-aminolevulinate synthase. Louis, C.A., Wood, S.G., Walton, H.S., Sinclair, P.R., Sinclair, J.F. Arch. Biochem. Biophys. (1998) [Pubmed]
 
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