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Gene Review

Cyp3a23/3a1  -  cytochrome P450, family 3, subfamily a,...

Rattus norvegicus

Synonyms: CYP, CYP3A23, CYPIIIA1, Cyp3a-1, Cyp3a1, ...
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Disease relevance of Cyp3a3


Psychiatry related information on Cyp3a3

  • Food deprivation and RU486 treatment also caused increases in CYP3A1, CYP3A18, and CYP3A23 mRNA, and the combined effects of these treatments on each of these mRNA forms were synergistic [6].

High impact information on Cyp3a3

  • We tested additional CYP inhibitors and found that cimetidine and sulfaphenazole, two CYP inhibitors that have no effect on mitochondrial protein synthesis, were also able to reduce creatine kinase release and infarct size in the Langendorff model [7].
  • Elements responsible for dexamethasone responsiveness of CYP3A23, a major glucocorticoid-inducible member of the CYP3A gene family, have been identified [8].
  • Gel-shift analysis demonstrated that glucocorticoid receptor did not associate with either DexRE-1 or -2; hence, glucocorticoid receptor does not directly mediate glucocorticoid induction of CYP3A23 [8].
  • We conclude that a primary mechanism for induction of CYP3A1 is stimulated transcription through a pathway activated by steroid hormones [9].
  • One CYP3A1 fragment (positions -220 to -56; 164 base pairs), which does not contain a traditional glucocorticoid responsive element, conferred dose-dependent DEX responsiveness independent of its orientation but not its position in pBLCAT2 [9].

Chemical compound and disease context of Cyp3a3


Biological context of Cyp3a3


Anatomical context of Cyp3a3


Associations of Cyp3a3 with chemical compounds

  • Selective induction of intestinal CYP3A23 by 1alpha,25-dihydroxyvitamin D3 in rats [23].
  • Phenobarbital (PB) and many structurally unrelated chemicals induce the protein and mRNA of P450 cytochromes CYP2B1, CYP2B2, CYP3A1, and specific phase II enzymes to a greater extent in Fischer 344 (F344) than in Wistar Furth (WF) female rats [24].
  • The maximum fold induction of mRNA varied: 2500-fold for CYP1A1 with BNF, 680-fold for CYP2B1 with PB, 59-fold for CYP3A23 with DEX, and 16-fold for CYP4A1 with CLO [25].
  • There was a modest (2- to 3-fold) increase in CYP3A1/2 activity and immunoreactive protein, as determined by 6 beta-hydroxylation of testosterone and Western blot analysis [26].
  • Here we show that addition of heme did not prevent the arsenite-mediated decreases in CYP3A23 protein, and arsenite did not decrease intracellular glutathione levels, indicating that heme and glutathione were not limiting for formation of holoCYP3A23 [18].

Other interactions of Cyp3a3


Analytical, diagnostic and therapeutic context of Cyp3a3

  • The induction of P450s in response to PB was affected by the nutritional status of the rats; mRNA levels of CYP2B1 and CYP3A1 after PB treatment, as assessed by quantitative real-time polymerase chain reaction analysis were reduced in the inulin-supplemented HF (HF+I) group, compared with those in the HF group [30].
  • RT-PCR analysis showed induction of cDNA of CYP1A1 and CYP3A1 by RFFE treatment [31].
  • Known substrates, inducers and inhibitors of CYP and inhibitor of P-gp were employed and metabolites were determined with HPLC [21].
  • These studies establish that drug-activating CYP genes may be useful for the development of novel combined chemotherapy/gene therapy strategies for cancer treatment utilizing established cancer chemotherapeutic agents [32].
  • Nevertheless, the gene expression of c/EBPalpha, GATA-2, and most of the CYP genes was dramatically reduced (up to 90%) in cell cultures lacking PECAM-1 expression; in strong contrast, expression of the silencer Oct-1 was massively increased (approximately 14-fold) [33].


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  2. Downregulation of Hepatic Cytochrome P-450 Isoforms and PPAR-gamma: Their Role in Hepatic Injury and Proinflammatory Responses in a Double-Hit Model of Hemorrhage and Sepsis. Higuchi, S., Wu, R., Zhou, M., Ravikumar, T.S., Wang, P. J. Surg. Res. (2007) [Pubmed]
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  4. Identification of a 16-nucleotide sequence that mediates post-transcriptional regulation of rat CYP2E1 by insulin. Moncion, A., Truong, N.T., Garrone, A., Beaune, P., Barouki, R., De Waziers, I. J. Biol. Chem. (2002) [Pubmed]
  5. Effect of chronic hypoxia on detoxication enzymes in rat liver. Shan, X., Aw, T.Y., Smith, E.R., Ingelman-Sundberg, M., Mannervik, B., Iyanagi, T., Jones, D.P. Biochem. Pharmacol. (1992) [Pubmed]
  6. Differential inducibility of specific mRNA corresponding to five CYP3A isoforms in female rat liver by RU486 and food deprivation: comparison with protein abundance and enzymic activities. Cheesman, M.J., Reilly, P.E. Biochem. Pharmacol. (1998) [Pubmed]
  7. Reduction of ischemia and reperfusion-induced myocardial damage by cytochrome P450 inhibitors. Granville, D.J., Tashakkor, B., Takeuchi, C., Gustafsson, A.B., Huang, C., Sayen, M.R., Wentworth, P., Yeager, M., Gottlieb, R.A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  8. Dexamethasone responsiveness of a major glucocorticoid-inducible CYP3A gene is mediated by elements unrelated to a glucocorticoid receptor binding motif. Huss, J.M., Wang, S.I., Astrom, A., McQuiddy, P., Kasper, C.B. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  9. Paradoxical transcriptional activation of rat liver cytochrome P-450 3A1 by dexamethasone and the antiglucocorticoid pregnenolone 16 alpha-carbonitrile: analysis by transient transfection into primary monolayer cultures of adult rat hepatocytes. Burger, H.J., Schuetz, J.D., Schuetz, E.G., Guzelian, P.S. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  10. Lack of cataleptogenic potentiation with non-imidazole H3 receptor antagonists reveals potential drug-drug interactions between imidazole-based H3 receptor antagonists and antipsychotic drugs. Zhang, M., Ballard, M.E., Pan, L., Roberts, S., Faghih, R., Cowart, M., Esbenshade, T.A., Fox, G.B., Decker, M.W., Hancock, A.A., Rueter, L.E. Brain Res. (2005) [Pubmed]
  11. Enhanced regional expression of glutathione S-transferase P1-1 with colocalized AP-1 and CYP 1A2 induction in chlorobenzene-induced porphyria. Thomas, R.S., Gustafson, D.L., Ramsdell, H.S., el-Masri, H.A., Benjamin, S.A., Yang, R.S. Toxicol. Appl. Pharmacol. (1998) [Pubmed]
  12. Lack of evidence for induction of CYP2B1, CYP3A23, and CYP1A2 gene expression by Panax ginseng and Panax quinquefolius extracts in adult rats and primary cultures of rat hepatocytes. Yu, C.T., Chen, J., Teng, X.W., Tong, V., Chang, T.K. Drug Metab. Dispos. (2005) [Pubmed]
  13. In vitro rat hepatic and intestinal metabolism of the organophosphate pesticides chlorpyrifos and diazinon. Poet, T.S., Wu, H., Kousba, A.A., Timchalk, C. Toxicol. Sci. (2003) [Pubmed]
  14. Effects of glucose on blood pressure and production of vascular aldosterone and corticosterone. Zhang, Y., Chu, L., Yu, W., Pang, J. Horm. Res. (2004) [Pubmed]
  15. Differences in transactivation between rat CYP3A1 and human CYP3A4 genes by human pregnane X receptor. Takada, T., Ogino, M., Miyata, M., Shimada, M., Nagata, K., Yamazoe, Y. Drug Metab. Pharmacokinet. (2004) [Pubmed]
  16. cDNA cloning and characterization of a novel member of steroid-induced cytochrome P450 3A in rats. Kirita, S., Matsubara, T. Arch. Biochem. Biophys. (1993) [Pubmed]
  17. Toxicity of the heterocyclic amine batracylin: investigation of rodent N-acetyltransferase activity and potential contribution of cytochrome P450 3A. Stevens, G.J., Burkey, J.L., McQueen, C.A. Cell Biol. Toxicol. (2000) [Pubmed]
  18. Mechanism of arsenite-mediated decreases in CYP3A23 in rat hepatocytes. Noreault, T.L., Jacobs, J.M., Nichols, R.C., Trask, H.W., Wrighton, S.A., Sinclair, P.R., Sinclair, J.F. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  19. Structure and expression of the rat CYP3A1 gene: isolation of the gene (P450/6betaB) and characterization of the recombinant protein. Nagata, K., Ogino, M., Shimada, M., Miyata, M., Gonzalez, F.J., Yamazoe, Y. Arch. Biochem. Biophys. (1999) [Pubmed]
  20. Preclinical pharmacokinetics and metabolism of 6-(4-(2,5-difluorophenyl)oxazol-5-yl)-3-isopropyl-[1,2,4]-triazolo[4,3-a]pyridine, a novel and selective p38alpha inhibitor: identification of an active metabolite in preclinical species and human liver microsomes. Kalgutkar, A.S., Hatch, H.L., Kosea, F., Nguyen, H.T., Choo, E.F., McClure, K.F., Taylor, T.J., Henne, K.R., Kuperman, A.V., Dombroski, M.A., Letavic, M.A. Biopharmaceutics & drug disposition. (2006) [Pubmed]
  21. An evaluation of para toluene-sulfonamide metabolism and effect with regard to CYP isoforms, P-glycoprotein, and drug interactions. Zhou, J.Q., Tang, Z.Q., Zhang, J.N. Die Pharmazie. (2006) [Pubmed]
  22. 7-ketocholesterol is an endogenous modulator for the arylhydrocarbon receptor. Savouret, J.F., Antenos, M., Quesne, M., Xu, J., Milgrom, E., Casper, R.F. J. Biol. Chem. (2001) [Pubmed]
  23. Selective induction of intestinal CYP3A23 by 1alpha,25-dihydroxyvitamin D3 in rats. Xu, Y., Iwanaga, K., Zhou, C., Cheesman, M.J., Farin, F., Thummel, K.E. Biochem. Pharmacol. (2006) [Pubmed]
  24. Phenobarbital induction of CYP2B1/2 in primary hepatocytes: endocrine regulation and evidence for a single pathway for multiple inducers. Ganem, L.G., Trottier, E., Anderson, A., Jefcoate, C.R. Toxicol. Appl. Pharmacol. (1999) [Pubmed]
  25. Cytochrome P450 gene induction in rats ex vivo assessed by quantitative real-time reverse transcriptase-polymerase chain reaction (TaqMan). Baldwin, S.J., Bramhall, J.L., Ashby, C.A., Yue, L., Murdock, P.R., Hood, S.R., Ayrton, A.D., Clarke, S.E. Drug Metab. Dispos. (2006) [Pubmed]
  26. Evaluation of octamethylcyclotetrasiloxane (D4) as an inducer of rat hepatic microsomal cytochrome P450, UDP-glucuronosyltransferase, and epoxide hydrolase: a 28-day inhalation study. McKim, J.M., Wilga, P.C., Kolesar, G.B., Choudhuri, S., Madan, A., Dochterman, L.W., Breen, J.G., Parkinson, A., Mast, R.W., Meeks, R.G. Toxicol. Sci. (1998) [Pubmed]
  27. Endocrine factors modulate the phenobarbital-mediated induction of cytochromes P450 and phase II enzymes in a similar strain-dependent manner. Ganem, L.G., Jefcoate, C.R. Toxicol. Appl. Pharmacol. (1998) [Pubmed]
  28. Expression and inducibility of cytochrome P450 3A9 (CYP3A9) and other members of the CYP3A subfamily in rat liver. Mahnke, A., Strotkamp, D., Roos, P.H., Hanstein, W.G., Chabot, G.G., Nef, P. Arch. Biochem. Biophys. (1997) [Pubmed]
  29. cAMP-associated inhibition of phenobarbital-inducible cytochrome P450 gene expression in primary rat hepatocyte cultures. Sidhu, J.S., Omiecinski, C.J. J. Biol. Chem. (1995) [Pubmed]
  30. 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 4{alpha} Expression. Sugatani, J., Wada, T., Osabe, M., Yamakawa, K., Yoshinari, K., Miwa, M. Drug Metab. Dispos. (2006) [Pubmed]
  31. Induction of hepatic cytochrome P450 isozymes, benzo(a)pyrene metabolism and DNA binding following exposure to polycyclic aromatic hydrocarbon residues generated during repeated fish fried oil in rats. Pandey, M.K., Yadav, S., Parmar, D., Das, M. Toxicol. Appl. Pharmacol. (2006) [Pubmed]
  32. Intratumoral activation and enhanced chemotherapeutic effect of oxazaphosphorines following cytochrome P-450 gene transfer: development of a combined chemotherapy/cancer gene therapy strategy. Chen, L., Waxman, D.J. Cancer Res. (1995) [Pubmed]
  33. Cellular dedifferentiation of endothelium is linked to activation and silencing of certain nuclear transcription factors: implications for endothelial dysfunction and vascular biology. Thum, T., Haverich, A., Borlak, J. FASEB J. (2000) [Pubmed]
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