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Gene Review

Ephx1  -  epoxide hydrolase 1, microsomal (xenobiotic)

Rattus norvegicus

Synonyms: Eph-1, Epoxide hydratase, Epoxide hydrolase 1, Microsomal epoxide hydrolase
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Disease relevance of Ephx1


High impact information on Ephx1


Chemical compound and disease context of Ephx1


Biological context of Ephx1


Anatomical context of Ephx1

  • This level of induction correlates well with the 5-fold induction in catalytic activity of epoxide hydrolase (using styrene 7,8-oxide as substrate) in microsomes isolated from phenobarbital-treated rats [18].
  • Therefore, we suggest that chronic phenobarbital administration increases the amount of functional epoxide hydrolase in rat liver microsomes by way of an increase in the translatable mRNA level encoding for the enzyme [18].
  • Liver poly(A)+RNA isolated from untreated and phenobarbital-treated rats has been translated in the rabbit reticulocyte cell-fre system in order to determine the level of translationally active epoxide hydrolase (EC mRNA [18].
  • These data further support the observation that hypomethylation of specific gene sequences occurs during chemical carcinogenesis and is correlated with an elevation in the steady state level of epoxide hydrolase mRNA in persistent hepatocyte nodules [19].
  • Hyperplastic nodule and hepatoma cytosol fractions had significant amounts of epoxide hydrolase, but normal liver cytosol fraction had no immunologically detectable hydrolase [2].

Associations of Ephx1 with chemical compounds


Physical interactions of Ephx1


Regulatory relationships of Ephx1

  • In contrast to the P-450s, microsomal epoxide hydrolase mRNAs were expressed at relative homogeneous amounts throughout the brain. beta-Naphthoflavone markedly increased the CYP1A1 and CYP1A2 mRNA contents of each brain region investigated, although this agent did not affect levels of epoxide hydrolase [24].
  • Three of four regimens increased epoxide hydrolase activity (150-600% of control) and DT-diaphorase activity (150-200% of control) [25].
  • Evidence was provided through kinetic studies that the epsilon-Gua adducts are formed primarily from 2-haloxiranes; consistent with this view, epoxide hydrolase inhibited the formation of N2,3-epsilon-Gua from vinyl chloride but alcohol dehydrogenase did not [26].

Other interactions of Ephx1


Analytical, diagnostic and therapeutic context of Ephx1


  1. Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Fahey, J.W., Zhang, Y., Talalay, P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  2. Quantiation of epoxide hydrolase released from hyperplastic nodule and hepatoma microsomes. Griffin, M.J., Noda, K. Cancer Res. (1980) [Pubmed]
  3. Transcriptional regulation of rat microsomal epoxide hydrolase gene by imidazole antimycotic agents. Kim, S.G. Mol. Pharmacol. (1992) [Pubmed]
  4. Induction of microsomal epoxide hydrolase by sulfur amino acid deprivation via the pathway of C-Jun N-terminal kinase and its extracellular exposure during cell death. Kang, K.W., Novak, R.F., Lee, C.H., Kim, S.G. Free Radic. Biol. Med. (2002) [Pubmed]
  5. Induction of alkoxyresorufin O-dealkylases, epoxide hydrolase, and liver weight gain: correlation with liver tumor-promoting potential in a series of barbiturates. Nims, R.W., Devor, D.E., Henneman, J.R., Lubet, R.A. Carcinogenesis (1987) [Pubmed]
  6. Antibodies against homogeneous epoxide hydratase provide evidence for a single enzyme hydrating styrene oxide and benz(a)pyrene 4,5-oxide. Oesch, F., Bentley, P. Nature (1976) [Pubmed]
  7. Cytosolic and microsomal epoxide hydrolases: differential properties in mammalian liver. Ota, K., Hammock, B.D. Science (1980) [Pubmed]
  8. Aryl hydrocarbon hydroxylase and epoxide hydratase activities: age effects in mammary epithelial cells of Sprague-Dawley rats. Greiner, J.W., Bryan, A.H., Malan-Shibley, L.B., Janss, D.H. J. Natl. Cancer Inst. (1980) [Pubmed]
  9. Epoxide hydrolase is a marker for the smooth endoplasmic reticulum in rat liver. Galteau, M.M., Antoine, B., Reggio, H. EMBO J. (1985) [Pubmed]
  10. Epoxidation reactions catalyzed by rat liver cytochromes P-450 and P-448 occur at different faces of the 8,9-double bond of 8-methylbenz[a]anthracene. Yang, S.K., Chou, M.W., Fu, P.P., Wislocki, P.G., Lu, A.H. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  11. Induction of rat liver microsomal epoxide hydrolase by thiazole and pyrazine: hydrolysis of 2-cyanoethylene oxide. Kim, S.G., Kedderis, G.L., Batra, R., Novak, R.F. Carcinogenesis (1993) [Pubmed]
  12. Induction of epoxide hydrolase in cultured rat hepatocytes and hepatoma cell lines. Razzouk, C., McManus, M.E., Hayashi, S., Schwartz, D., Thorgeirsson, S.S. Biochem. Pharmacol. (1985) [Pubmed]
  13. Toxicogenomics of bromobenzene hepatotoxicity: a combined transcriptomics and proteomics approach. Heijne, W.H., Stierum, R.H., Slijper, M., van Bladeren, P.J., van Ommen, B. Biochem. Pharmacol. (2003) [Pubmed]
  14. Prevention of c-Jun/activator protein-1 activation and microsomal epoxide hydrolase induction in the rat liver by cysteine during protein-calorie malnutrition. Cho, M.K., Kim, Y.G., Lee, M.G., Kim, S.G. Biochem. Pharmacol. (2001) [Pubmed]
  15. Effects of model traumatic injury on hepatic drug metabolism in the rat. VI. Major detoxification/toxification pathways. Griffeth, L.K., Rosen, G.M., Rauchman, E.J. Drug Metab. Dispos. (1987) [Pubmed]
  16. Structure and organization of the microsomal xenobiotic epoxide hydrolase gene. Falany, C.N., McQuiddy, P., Kasper, C.B. J. Biol. Chem. (1987) [Pubmed]
  17. Complementary DNA and amino acid sequence of rat liver microsomal, xenobiotic epoxide hydrolase. Porter, T.D., Beck, T.W., Kasper, C.B. Arch. Biochem. Biophys. (1986) [Pubmed]
  18. Effect of phenobarbital on the level of translatable rat liver epoxide hydrolase mRNA. Pickett, C.B., Lu, A.Y. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  19. Regulation of microsomal, xenobiotic epoxide hydrolase messenger RNA in persistent hepatocyte nodules and hepatomas induced by chemical carcinogens. Ding, V.D., Cameron, R., Pickett, C.B. Cancer Res. (1990) [Pubmed]
  20. 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]
  21. Metabolic pathways of 7,12-dimethylbenz[a]anthracene in hepatic microsomes. Yang, S.K., Dower, W.V. Proc. Natl. Acad. Sci. U.S.A. (1975) [Pubmed]
  22. Enzymatic conversion of benzo(a)pyrene leading predominantly to the diol-epoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene through a single enantiomer of r-7, t-8-dihydroxy-7,8-dihydrobenzo(a)pyrene. Yang, S.K., McCourt, D.W., Roller, P.P., Gelboin, H.V. Proc. Natl. Acad. Sci. U.S.A. (1976) [Pubmed]
  23. Alcohol dehydrogenase-coupled spectrophotometric assay of epoxide hydratase activity. Guengerich, F.P., Mason, P.S. Anal. Biochem. (1980) [Pubmed]
  24. Regional distribution and expression modulation of cytochrome P-450 and epoxide hydrolase mRNAs in the rat brain. Schilter, B., Omiecinski, C.J. Mol. Pharmacol. (1993) [Pubmed]
  25. Comparison of hepatic carcinogen initiation-promotion systems. Leonard, T.B., Dent, J.G., Graichen, M.E., Lyght, O., Popp, J.A. Carcinogenesis (1982) [Pubmed]
  26. Formation of 1,N2- and N2,3-ethenoguanine from 2-halooxiranes: isotopic labeling studies and isolation of a hemiaminal derivative of N2-(2-oxoethyl)guanine. Guengerich, F.P., Persmark, M., Humphreys, W.G. Chem. Res. Toxicol. (1993) [Pubmed]
  27. Tumor necrosis factor alpha blockade increases renal Cyp2c23 expression and slows the progression of renal damage in salt-sensitive hypertension. Elmarakby, A.A., Quigley, J.E., Pollock, D.M., Imig, J.D. Hypertension (2006) [Pubmed]
  28. Multiplicity of induction patterns of rat liver microsomal mono-oxygenases and other polypeptides produced by administration of various xenobiotics. Sharma, R.N., Cameron, R.G., Farber, E., Griffin, M.J., Joly, J.G., Murray, R.K. Biochem. J. (1979) [Pubmed]
  29. Denaturation of cytochrome P-450 by indomethacin and other non-steroidal anti-inflammatory drugs: evidence for a surfactant mechanism and a selective effect of a p-chlorophenyl moiety. Falzon, M., Nielsch, A., Burke, M.D. Biochem. Pharmacol. (1986) [Pubmed]
  30. 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]
  31. Metabolism of benzo(a)pyrene by subcellular fractions of rat liver: evidence for similar patterns of cytochrome P-450 in rough and smooth endoplasmic reticulum but not in nuclei and plasma membrane. Oesch, F., Bentley, P., Golan, M., Stasiecki, P. Cancer Res. (1985) [Pubmed]
  32. Regulation of three forms of cytochrome P-450 and epoxide hydrolase in rat liver microsomes. Effects of age, sex, and induction. Thomas, P.E., Reik, L.M., Ryan, D.E., Levin, W. J. Biol. Chem. (1981) [Pubmed]
  33. Studies on the proliferation and fate of oval cells in the liver of rats treated with 2-acetylaminofluorene and partial hepatectomy. Tatematsu, M., Ho, R.H., Kaku, T., Ekem, J.K., Farber, E. Am. J. Pathol. (1984) [Pubmed]
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