Archives of Toxicology

, Volume 83, Issue 4, pp 297–318

Mammalian epoxide hydrolases in xenobiotic metabolism and signalling

Review Article

Abstract

Epoxide hydrolases catalyse the hydrolysis of electrophilic—and therefore potentially genotoxic—epoxides to the corresponding less reactive vicinal diols, which explains the classification of epoxide hydrolases as typical detoxifying enzymes. The best example is mammalian microsomal epoxide hydrolase (mEH)—an enzyme prone to detoxification—due to a high expression level in the liver, a broad substrate selectivity, as well as inducibility by foreign compounds. The mEH is capable of inactivating a large number of structurally different, highly reactive epoxides and hence is an important part of the enzymatic defence of our organism against adverse effects of foreign compounds. Furthermore, evidence is accumulating that mammalian epoxide hydrolases play physiological roles other than detoxification, particularly through involvement in signalling processes. This certainly holds true for soluble epoxide hydrolase (sEH) whose main function seems to be the turnover of lipid derived epoxides, which are signalling lipids with diverse functions in regulatory processes, such as control of blood pressure, inflammatory processes, cell proliferation and nociception. In recent years, the sEH has attracted attention as a promising target for pharmacological inhibition to treat hypertension and possibly other diseases. Recently, new hitherto uncharacterised epoxide hydrolases could be identified in mammals by genome analysis. The expression pattern and substrate selectivity of these new epoxide hydrolases suggests their participation in signalling processes rather than a role in detoxification. Taken together, epoxide hydrolases (1) play a central role in the detoxification of genotoxic epoxides and (2) have an important function in the regulation of physiological processes by the control of signalling molecules with an epoxide structure.

Keywords

Epoxide hydrolase Xenobiotic metabolism EPHX ABHD Lipid signalling peg1/MEST EET Cholesterol Lipid phosphatase 

References

  1. Ai D, Fu Y, Guo D, Tanaka H, Wang N, Tang C, Hammock BD, Shyy JY, Zhu Y (2007) Angiotensin II up-regulates soluble epoxide hydrolase in vascular endothelium in vitro and in vivo. Proc Natl Acad Sci USA 104:9018–9023. doi:10.1073/pnas.0703229104 PubMedGoogle Scholar
  2. Ala U, Piro RM, Grassi E, Damasco C, Silengo L, Oti M, Provero P, Di Cunto F (2008) Prediction of human disease genes by human-mouse conserved coexpression analysis. PLoS Comput Biol 4:e1000043. doi:10.1371/journal.pcbi.1000043 PubMedGoogle Scholar
  3. Allen KN, Dunaway-Mariano D (2004) Phosphoryl group transfer: evolution of a catalytic scaffold. Trends Biochem Sci 29:495–503. doi:10.1016/j.tibs.2004.07.008 PubMedGoogle Scholar
  4. Anton R, Puig L, Esgleyes T, de Moragas JM, Vila L (1998) Occurrence of hepoxilins and trioxilins in psoriatic lesions. J Invest Dermatol 110:303–310. doi:10.1046/j.1523-1747.1998.00159.x PubMedGoogle Scholar
  5. Arand M, Knehr M, Thomas H, Zeller HD, Oesch F (1991) An impaired peroxisomal targeting sequence leading to an unusual bicompartmental distribution of cytosolic epoxide hydrolase. FEBS Lett 294:19–22. doi:10.1016/0014-5793(91)81333-4 PubMedGoogle Scholar
  6. Arand M, Grant DF, Beetham JK, Friedberg T, Oesch F, Hammock BD (1994) Sequence similarity of mammalian epoxide hydrolases to the bacterial haloalkane dehalogenase and other related proteins. Implication for the potential catalytic mechanism of enzymatic epoxide hydrolysis. FEBS Lett 338:251–256. doi:10.1016/0014-5793(94)80278-5 PubMedGoogle Scholar
  7. Arand M, Wagner H, Oesch F (1996) Asp333, Asp495, and His523 form the catalytic triad of rat soluble epoxide hydrolase. J Biol Chem 271:4223–4229. doi:10.1074/jbc.271.8.4223 PubMedGoogle Scholar
  8. Arand M, Hemmer H, Durk H, Baratti J, Archelas A, Furstoss R, Oesch F (1999a) Cloning and molecular characterization of a soluble epoxide hydrolase from Aspergillus niger that is related to mammalian microsomal epoxide hydrolase. Biochem J 344(Pt 1):273–280. doi:10.1042/0264-6021:3440273 PubMedGoogle Scholar
  9. Arand M, Muller F, Mecky A, Hinz W, Urban P, Pompon D, Kellner R, Oesch F (1999b) Catalytic triad of microsomal epoxide hydrolase: replacement of Glu404 with Asp leads to a strongly increased turnover rate. Biochem J 337(Pt 1):37–43. doi:10.1042/0264-6021:3370037 PubMedGoogle Scholar
  10. Arand M, Cronin A, Oesch F, Mowbray SL, Jones TA (2003a) The telltale structures of epoxide hydrolases. Drug Metab Rev 35:365–383. doi:10.1081/DMR-120026498 PubMedGoogle Scholar
  11. Arand M, Hallberg BM, Zou J, Bergfors T, Oesch F, van der Werf MJ, de Bont JA, Jones TA, Mowbray SL (2003b) Structure of Rhodococcus erythropolis limonene-1, 2-epoxide hydrolase reveals a novel active site. EMBO J 22:2583–2592. doi:10.1093/emboj/cdg275 PubMedGoogle Scholar
  12. Arand M, Herrero Plana ME, Hengstler JG, Lohmann M, Cronin A, Oesch F (2003c) Detoxification strategy of epoxide hydrolase—the basis for a threshold in chemical carcinogenesis. EXCLI J 2:22–30Google Scholar
  13. Argiriadi MA, Morisseau C, Hammock BD, Christianson DW (1999) Detoxification of environmental mutagens and carcinogens: structure, mechanism, and evolution of liver epoxide hydrolase. Proc Natl Acad Sci USA 96:10637–10642. doi:10.1073/pnas.96.19.10637 PubMedGoogle Scholar
  14. Aringer L, Eneroth P (1974) Formation and metabolism in vitro of 5, 6-epoxides of cholesterol and beta-sitosterol. J Lipid Res 15:389–398PubMedGoogle Scholar
  15. Armstrong RN (1987) Enzyme-catalyzed detoxication reactions: mechanisms and stereochemistry. CRC Crit Rev Biochem 22:39–88. doi:10.3109/10409238709082547 PubMedGoogle Scholar
  16. Armstrong RN, Cassidy CS (2000) New structural and chemical insight into the catalytic mechanism of epoxide hydrolases. Drug Metab Rev 32:327–338. doi:10.1081/DMR-100102337 PubMedGoogle Scholar
  17. Astrom A, Eriksson M, Eriksson LC, Birberg W, Pilotti A, DePierre JW (1986) Subcellular and organ distribution of cholesterol epoxide hydrolase in the rat. Biochim Biophys Acta 882:359–366PubMedGoogle Scholar
  18. Astrom A, Maner S, DePierre JW (1987) Induction of liver microsomal epoxide hydrolase, UDP-glucuronyl transferase and cytosolic glutathione transferase in different rodent species by 2-acetylaminofluorene or 3-methylcholanthrene. Xenobiotica 17:155–163PubMedCrossRefGoogle Scholar
  19. Baker AS, Ciocci MJ, Metcalf WW, Kim J, Babbitt PC, Wanner BL, Martin BM, Dunaway-Mariano D (1998) Insights into the mechanism of catalysis by the P-C bond-cleaving enzyme phosphonoacetaldehyde hydrolase derived from gene sequence analysis and mutagenesis. Biochemistry 37:9305–9315. doi:10.1021/bi972677d PubMedGoogle Scholar
  20. Barbirato F, Verdoes JC, de Bont JA, van der Werf MJ (1998) The Rhodococcus erythropolis DCL14 limonene-1, 2-epoxide hydrolase gene encodes an enzyme belonging to a novel class of epoxide hydrolases. FEBS Lett 438:293–296. doi:10.1016/S0014-5793(98)01322-2 PubMedGoogle Scholar
  21. Beetham JK, Tian T, Hammock BD (1993) cDNA cloning and expression of a soluble epoxide hydrolase from human liver. Arch Biochem Biophys 305:197–201. doi:10.1006/abbi.1993.1411 PubMedGoogle Scholar
  22. Beetham JK, Grant D, Arand M, Garbarino J, Kiyosue T, Pinot F, Oesch F, Belknap WR, Shinozaki K, Hammock BD (1995) Gene evolution of epoxide hydrolases and recommended nomenclature. DNA Cell Biol 14:61–71PubMedGoogle Scholar
  23. Bellucci G, Berti G, Chiappe C, Lippi A, Marioni F (1987) The metabolism of carbamazepine in humans: steric course of the enzymatic hydrolysis of the 10, 11-epoxide. J Med Chem 30:768–773. doi:10.1021/jm00388a004 PubMedGoogle Scholar
  24. Bentley P, Schmassmann H, Sims P, Oesch F (1976) Epoxides derived from various polycyclic hydrocarbons as substrates of homogeneous and microsome-bound epoxide hydratase. A general assay and kinetic properties. Eur J Biochem 69:97–103. doi:10.1111/j.1432-1033.1976.tb10862.x PubMedGoogle Scholar
  25. Black HS, Douglas DR (1972) A model system for the evaluation of the role of cholesterol-oxide in ultraviolet carcinogenesis. Cancer Res 32:2630–2632PubMedGoogle Scholar
  26. Brash AR, Yu Z, Boeglin WE, Schneider C (2007) The hepoxilin connection in the epidermis. FEBS J 274:3494–3502. doi:10.1111/j.1742-4658.2007.05909.x PubMedGoogle Scholar
  27. Brogger J, Steen VM, Eiken HG, Gulsvik A, Bakke P (2006) Genetic association between COPD and polymorphisms in TNF, ADRB2 and EPHX1. Eur Respir J 27:682–688. doi:10.1183/09031936.06.00057005 PubMedGoogle Scholar
  28. Burdon KP, Lehtinen AB, Langefeld CD, Carr JJ, Rich SS, Freedman BI, Herrington D, Bowden DW (2008) Genetic analysis of the soluble epoxide hydrolase gene, EPHX2, in subclinical cardiovascular disease in the Diabetes Heart Study. Diab Vasc Dis Res 5:128–134. doi:10.3132/dvdr.2008.021 PubMedGoogle Scholar
  29. Chan JT, Black HS (1976) Distribution of cholesterol-5alpha, 6alpha-epoxide formation and its metabolism in mouse skin. J Invest Dermatol 66:112–116. doi:10.1111/1523-1747.ep12481460 PubMedGoogle Scholar
  30. Chen X, Wang S, Wu N, Yang CS (2004) Leukotriene A4 hydrolase as a target for cancer prevention and therapy. Curr Cancer Drug Targets 4:267–283. doi:10.2174/1568009043333041 PubMedGoogle Scholar
  31. Coller JK, Fritz P, Zanger UM, Siegle I, Eichelbaum M, Kroemer HK, Murdter TE (2001) Distribution of microsomal epoxide hydrolase in humans: an immunohistochemical study in normal tissues, and benign and malignant tumours. Histochem J 33:329–336. doi:10.1023/A:1012414806166 PubMedGoogle Scholar
  32. Cottrell S, Jung K, Kristiansen G, Eltze E, Semjonow A, Ittmann M, Hartmann A, Stamey T, Haefliger C, Weiss G (2007) Discovery and validation of 3 novel DNA methylation markers of prostate cancer prognosis. J Urol 177:1753–1758. doi:10.1016/j.juro.2007.01.010 PubMedGoogle Scholar
  33. Cronin A, Mowbray S, Durk H, Homburg S, Fleming I, Fisslthaler B, Oesch F, Arand M (2003) The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase. Proc Natl Acad Sci USA 100:1552–1557. doi:10.1073/pnas.0437829100 PubMedGoogle Scholar
  34. Cronin A, Homburg S, Durk H, Richter I, Adamska M, Frere F, Arand M (2008) Insights into the catalytic mechanism of human sEH phosphatase by site-directed mutagenesis and LC-MS/MS analysis. J Mol Biol 383:627–640. doi:10.1016/j.jmb.2008.08.049 PubMedGoogle Scholar
  35. Csanady GA, Kessler W, Hoffmann HD, Filser JG (2003) A toxicokinetic model for styrene and its metabolite styrene-7, 8-oxide in mouse, rat and human with special emphasis on the lung. Toxicol Lett 138:75–102. doi:10.1016/S0378-4274(02)00409-5 PubMedGoogle Scholar
  36. Dash B, Afriyie-Gyawu E, Huebner HJ, Porter W, Wang JS, Jolly PE, Phillips TD (2007) Determinants of the variability of aflatoxin-albumin adduct levels in Ghanaians. J Toxicol Environ Health A 70:58–66. doi:10.1080/15287390600748880 PubMedGoogle Scholar
  37. Derewlany LO, Pace-Asciak CR, Radde IC (1984) Hepoxilin A, hydroxyepoxide metabolite of arachidonic acid, stimulates transport of 45Ca across the guinea pig visceral yolk sac. Can J Physiol Pharmacol 62:1466–1469PubMedGoogle Scholar
  38. Dietze EC, Kuwano E, Casas J, Hammock BD (1991) Inhibition of cytosolic epoxide hydrolase by trans-3-phenylglycidols. Biochem Pharmacol 42:1163–1175. doi:10.1016/0006-2952(91)90250-9 PubMedGoogle Scholar
  39. Dietze EC, Stephens J, Magdalou J, Bender DM, Moyer M, Fowler B, Hammock BD (1993) Inhibition of human and murine cytosolic epoxide hydrolase by group-selective reagents. Comp Biochem Physiol B 104:299–308. doi:10.1016/0305-0491(93)90372-C PubMedGoogle Scholar
  40. Elfstrom LT, Widersten M (2006) Implications for an ionized alkyl-enzyme intermediate during StEH1-catalyzed trans-stilbene oxide hydrolysis. Biochemistry 45:205–212. doi:10.1021/bi051893g PubMedGoogle Scholar
  41. Enayetallah AE, French RA, Thibodeau MS, Grant DF (2004) Distribution of soluble epoxide hydrolase and of cytochrome P450 2C8, 2C9, and 2J2 in human tissues. J Histochem Cytochem 52:447–454PubMedGoogle Scholar
  42. Enayetallah AE, Grant DF (2006) Effects of human soluble epoxide hydrolase polymorphisms on isoprenoid phosphate hydrolysis. Biochem Biophys Res Commun 341:254–260. doi:10.1016/j.bbrc.2005.12.180 PubMedGoogle Scholar
  43. Enayetallah AE, French RA, Barber M, Grant DF (2006a) Cell-specific subcellular localization of soluble epoxide hydrolase in human tissues. J Histochem Cytochem 54:329–335. doi:10.1369/jhc.5A6808.2005 PubMedGoogle Scholar
  44. Enayetallah AE, French RA, Grant DF (2006b) Distribution of soluble epoxide hydrolase, cytochrome P450 2C8, 2C9 and 2J2 in human malignant neoplasms. J Mol Histol 37:133–141. doi:10.1007/s10735-006-9050-9 PubMedGoogle Scholar
  45. Epp N, Furstenberger G, Muller K, de Juanes S, Leitges M, Hausser I, Thieme F, Liebisch G, Schmitz G, Krieg P (2007) 12R-lipoxygenase deficiency disrupts epidermal barrier function. J Cell Biol 177:173–182. doi:10.1083/jcb.200612116 PubMedGoogle Scholar
  46. Evans JF, Dupuis P, Ford-Hutchinson AW (1985) Purification and characterisation of leukotriene A4 hydrolase from rat neutrophils. Biochim Biophys Acta 840:43–50PubMedGoogle Scholar
  47. Falany CN, McQuiddy P, Kasper CB (1987) Structure and organization of the microsomal xenobiotic epoxide hydrolase gene. J Biol Chem 262:5924–5930PubMedGoogle Scholar
  48. Falck JR, Krishna UM, Reddy YK, Kumar PS, Reddy KM, Hittner SB, Deeter C, Sharma KK, Gauthier KM, Campbell WB (2003) Comparison of vasodilatory properties of 14, 15-EET analogs: structural requirements for dilation. Am J Physiol Heart Circ Physiol 284:H337–H349PubMedGoogle Scholar
  49. Fandrich F, Degiuli B, Vogel-Bindel U, Arand M, Oesch F (1995) Induction of rat liver microsomal epoxide hydrolase by its endogenous substrate 16 alpha, 17 alpha-epoxyestra-1, 3, 5-trien-3-ol. Xenobiotica 25:239–244PubMedGoogle Scholar
  50. Fang X (2006) Soluble epoxide hydrolase: a novel target for the treatment of hypertension. Recent Pat Cardiovasc Drug Discov 1:67–72PubMedGoogle Scholar
  51. Fang X, Kaduce TL, Weintraub NL, Harmon S, Teesch LM, Morisseau C, Thompson DA, Hammock BD, Spector AA (2001) Pathways of epoxyeicosatrienoic acid metabolism in endothelial cells. Implications for the vascular effects of soluble epoxide hydrolase inhibition. J Biol Chem 276:14867–14874. doi:10.1074/jbc.M011761200 PubMedGoogle Scholar
  52. Fillgrove KL, Pakhomova S, Newcomer ME, Armstrong RN (2003) Mechanistic diversity of fosfomycin resistance in pathogenic microorganisms. J Am Chem Soc 125:15730–15731. doi:10.1021/ja039307z PubMedGoogle Scholar
  53. Finley BL, Hammock BD (1988) Increased cholesterol epoxide hydrolase activity in clofibrate-fed animals. Biochem Pharmacol 37:3169–3175. doi:10.1016/0006-2952(88)90316-4 PubMedGoogle Scholar
  54. Fisslthaler B, Popp R, Kiss L, Potente M, Harder DR, Fleming I, Busse R (1999) Cytochrome P450 2C is an EDHF synthase in coronary arteries. Nature 401:493–497. doi:10.1038/46816 PubMedGoogle Scholar
  55. Fornage M, Boerwinkle E, Doris PA, Jacobs D, Liu K, Wong ND (2004) Polymorphism of the soluble epoxide hydrolase is associated with coronary artery calcification in African-American subjects: The Coronary Artery Risk Development in Young Adults (CARDIA) study. Circulation 109:335–339. doi:10.1161/01.CIR.0000109487.46725.02 PubMedGoogle Scholar
  56. Franken SM, Rozeboom HJ, Kalk KH, Dijkstra BW (1991) Crystal structure of haloalkane dehalogenase: an enzyme to detoxify halogenated alkanes. EMBO J 10:1297–1302PubMedGoogle Scholar
  57. Friedberg T, Becker R, Oesch F, Glatt H (1994a) Studies on the importance of microsomal epoxide hydrolase in the detoxification of arene oxides using the heterologous expression of the enzyme in mammalian cells. Carcinogenesis 15:171–175. doi:10.1093/carcin/15.2.171 PubMedGoogle Scholar
  58. Friedberg T, Lollmann B, Becker R, Holler R, Oesch F (1994b) The microsomal epoxide hydrolase has a single membrane signal anchor sequence which is dispensable for the catalytic activity of this protein. Biochem J 303(Pt 3):967–972PubMedGoogle Scholar
  59. Funk CD, Radmark O, Fu JY, Matsumoto T, Jornvall H, Shimizu T, Samuelsson B (1987) Molecular cloning and amino acid sequence of leukotriene A4 hydrolase. Proc Natl Acad Sci USA 84:6677–6681. doi:10.1073/pnas.84.19.6677 PubMedGoogle Scholar
  60. Furuta J, Nobeyama Y, Umebayashi Y, Otsuka F, Kikuchi K, Ushijima T (2006) Silencing of Peroxiredoxin 2 and aberrant methylation of 33 CpG islands in putative promoter regions in human malignant melanomas. Cancer Res 66:6080–6086. doi:10.1158/0008-5472.CAN-06-0157 PubMedGoogle Scholar
  61. Gaedigk A, Leeder JS, Grant DM (1997) Tissue-specific expression and alternative splicing of human microsomal epoxide hydrolase. DNA Cell Biol 16:1257–1266PubMedGoogle Scholar
  62. Gao J, Lauer FT, Mitchell LA, Burchiel SW (2007) Microsomal expoxide hydrolase is required for 7, 12-dimethylbenz[a]anthracene (DMBA)-induced immunotoxicity in mice. Toxicol Sci 98:137–144. doi:10.1093/toxsci/kfm089 PubMedGoogle Scholar
  63. Gomez GA, Morisseau C, Hammock BD, Christianson DW (2004) Structure of human epoxide hydrolase reveals mechanistic inferences on bifunctional catalysis in epoxide and phosphate ester hydrolysis. Biochemistry 43:4716–4723. doi:10.1021/bi036189j PubMedGoogle Scholar
  64. Gonzalez FJ, Kasper CB (1981) Cloning of epoxide hydratase complementary DNA. J Biol Chem 256:4697–4700PubMedGoogle Scholar
  65. Grant DF, Storms DH, Hammock BD (1993) Molecular cloning and expression of murine liver soluble epoxide hydrolase. J Biol Chem 268:17628–17633PubMedGoogle Scholar
  66. Griffin KJ, Gierse J, Krivi G, Fitzpatrick FA (1992) Opioid peptides are substrates for the bifunctional enzyme LTA4 hydrolase/aminopeptidase. Prostaglandins 44:251–257. doi:10.1016/0090-6980(92)90018-O PubMedGoogle Scholar
  67. Gschwendtner A, Ripke S, Freilinger T, Lichtner P, Muller-Myhsok B, Wichmann HE, Meitinger T, Dichgans M (2008) Genetic variation in soluble epoxide hydrolase (EPHX2) is associated with an increased risk of ischemic stroke in white Europeans. Stroke 39:1593–1596. doi:10.1161/STROKEAHA.107.502179 PubMedGoogle Scholar
  68. Guengerich FP, Johnson WW, Shimada T, Ueng YF, Yamazaki H, Langouet S (1998) Activation and detoxication of aflatoxin B1. Mutat Res 402:121–128. doi:10.1016/S0027-5107(97)00289-3 PubMedGoogle Scholar
  69. Habalova V, Salagovic J, Kalina I, Stubna J (2004) Combined analysis of polymorphisms in glutathione S-transferase M1 and microsomal epoxide hydrolase in lung cancer patients. Neoplasma 51:352–357PubMedGoogle Scholar
  70. Haeggstrom JZ (2004) Leukotriene A4 hydrolase/aminopeptidase, the gatekeeper of chemotactic leukotriene B4 biosynthesis. J Biol Chem 279:50639–50642. doi:10.1074/jbc.R400027200 PubMedGoogle Scholar
  71. Haeggstrom JZ, Wetterholm A, Vallee BL, Samuelsson B (1990) Leukotriene A4 hydrolase: an epoxide hydrolase with peptidase activity. Biochem Biophys Res Commun 173:431–437. doi:10.1016/S0006-291X(05)81076-9 PubMedGoogle Scholar
  72. Haeggstrom JZ, Kull F, Rudberg PC, Tholander F, Thunnissen MM (2002) Leukotriene A4 hydrolase. Prostaglandins Other Lipid Mediat 68–69:495–510. doi:10.1016/S0090-6980(02)00051-5 PubMedGoogle Scholar
  73. Haeggstrom JZ, Tholander F, Wetterholm A (2007) Structure and catalytic mechanisms of leukotriene A4 hydrolase. Prostaglandins Other Lipid Mediat 83:198–202. doi:10.1016/j.prostaglandins.2007.01.006 PubMedGoogle Scholar
  74. Harris TR, Aronov PA, Jones PD, Tanaka H, Arand M, Hammock BD (2008) Identification of two epoxide hydrolases in Caenorhabditis elegans that metabolize mammalian lipid signaling molecules. Arch Biochem BiophysGoogle Scholar
  75. Hassett C, Turnblom SM, DeAngeles A, Omiecinski CJ (1989) Rabbit microsomal epoxide hydrolase: isolation and characterization of the xenobiotic metabolizing enzyme cDNA. Arch Biochem Biophys 271:380–389. doi:10.1016/0003-9861(89)90287-7 PubMedGoogle Scholar
  76. Hassett C, Aicher L, Sidhu JS, Omiecinski CJ (1994) Human microsomal epoxide hydrolase: genetic polymorphism and functional expression in vitro of amino acid variants. Hum Mol Genet 3:421–428. doi:10.1093/hmg/3.3.421 PubMedGoogle Scholar
  77. Hassett C, Lin J, Carty CL, Laurenzana EM, Omiecinski CJ (1997) Human hepatic microsomal epoxide hydrolase: comparative analysis of polymorphic expression. Arch Biochem Biophys 337:275–283. doi:10.1006/abbi.1996.9794 PubMedGoogle Scholar
  78. Hengstler JG, Arand M, Herrero ME, Oesch F (1998) Polymorphisms of N-acetyltransferases, glutathione S-transferases, microsomal epoxide hydrolase and sulfotransferases: influence on cancer susceptibility. Recent Results Cancer Res 154:47–85PubMedGoogle Scholar
  79. Hennebold JD, Mah K, Perez W, Vance JE, Stouffer RL, Morisseau C, Hammock BD, Adashi EY (2005) Identification and characterization of an ovary-selective isoform of epoxide hydrolase. Biol Reprod 72:968–975. doi:10.1095/biolreprod.104.035899 PubMedGoogle Scholar
  80. Herrero ME, Arand M, Hengstler JG, Oesch F (1997) Recombinant expression of human microsomal epoxide hydrolase protects V79 Chinese hamster cells from styrene oxide—but not from ethylene oxide-induced DNA strand breaks. Environ Mol Mutagen 30:429–439. doi:10.1002/(SICI)1098-2280(1997)30:4<429::AID-EM8>3.0.CO;2-D PubMedGoogle Scholar
  81. Holder G, Yagi H, Dansette P, Jerina DM, Levin W, Lu AY, Conney AH (1974) Effects of inducers and epoxide hydrase on the metabolism of benzo[a]pyrene by liver microsomes and a reconstituted system: analysis by high pressure liquid chromatography. Proc Natl Acad Sci USA 71:4356–4360. doi:10.1073/pnas.71.11.4356 PubMedGoogle Scholar
  82. Holler R, Arand M, Mecky A, Oesch F, Friedberg T (1997) The membrane anchor of microsomal epoxide hydrolase from human, rat, and rabbit displays an unexpected membrane topology. Biochem Biophys Res Commun 236:754–759. doi:10.1006/bbrc.1997.7044 PubMedGoogle Scholar
  83. Holmquist M (2000) Alpha/beta-hydrolase fold enzymes: structures, functions and mechanisms. Curr Protein Pept Sci 1:209–235. doi:10.2174/1389203003381405 PubMedGoogle Scholar
  84. Honscha W, Platte HD, Oesch F, Friedberg T (1995) Relationship between the microsomal epoxide hydrolase and the hepatocellular transport of bile acids and xenobiotics. Biochem J 311(Pt 3):975–979PubMedGoogle Scholar
  85. Hu S, Kim HS (1993) Activation of K+ channel in vascular smooth muscles by cytochrome P450 metabolites of arachidonic acid. Eur J Pharmacol 230:215–221. doi:10.1016/0014-2999(93)90805-R PubMedGoogle Scholar
  86. Imig JD (2005) Epoxide hydrolase and epoxygenase metabolites as therapeutic targets for renal diseases. Am J Physiol Renal Physiol 289:F496–F503. doi:10.1152/ajprenal.00350.2004 PubMedGoogle Scholar
  87. Imig JD, Navar LG, Roman RJ, Reddy KK, Falck JR (1996) Actions of epoxygenase metabolites on the preglomerular vasculature. J Am Soc Nephrol 7:2364–2370PubMedGoogle Scholar
  88. Imig JD, Zhao X, Capdevila JH, Morisseau C, Hammock BD (2002) Soluble epoxide hydrolase inhibition lowers arterial blood pressure in angiotensin II hypertension. Hypertension 39:690–694. doi:10.1161/hy0202.103788 PubMedGoogle Scholar
  89. Inceoglu B, Jinks SL, Schmelzer KR, Waite T, Kim IH, Hammock BD (2006) Inhibition of soluble epoxide hydrolase reduces LPS-induced thermal hyperalgesia and mechanical allodynia in a rat model of inflammatory pain. Life Sci 79:2311–2319. doi:10.1016/j.lfs.2006.07.031 PubMedGoogle Scholar
  90. Janssen DB, Pries F, van der Ploeg J, Kazemier B, Terpstra P, Witholt B (1989) Cloning of 1, 2-dichloroethane degradation genes of Xanthobacter autotrophicus GJ10 and expression and sequencing of the dhlA gene. J Bacteriol 171:6791–6799PubMedGoogle Scholar
  91. Johansson C, Stark A, Sandberg M, Ek B, Rask L, Meijer J (1995) Tissue specific basal expression of soluble murine epoxide hydrolase and effects of clofibrate on the mRNA levels in extrahepatic tissues and liver. Arch Toxicol 70:61–63. doi:10.1007/s002040050250 PubMedGoogle Scholar
  92. Johansson P, Unge T, Cronin A, Arand M, Bergfors T, Jones TA, Mowbray SL (2005) Structure of an atypical epoxide hydrolase from Mycobacterium tuberculosis gives insights into its function. J Mol Biol 351:1048–1056. doi:10.1016/j.jmb.2005.06.055 PubMedGoogle Scholar
  93. Kaneko-Ishino T, Kuroiwa Y, Miyoshi N, Kohda T, Suzuki R, Yokoyama M, Viville S, Barton SC, Ishino F, Surani MA (1995) Peg1/Mest imprinted gene on chromosome 6 identified by cDNA subtraction hybridization. Nat Genet 11:52–59. doi:10.1038/ng0995-52 PubMedGoogle Scholar
  94. Kelly EJ, Erickson KE, Sengstag C, Eaton DL (2002) Expression of human microsomal epoxide hydrolase in Saccharomyces cerevisiae reveals a functional role in aflatoxin B1 detoxification. Toxicol Sci 65:35–42. doi:10.1093/toxsci/65.1.35 PubMedGoogle Scholar
  95. Kim IH, Morisseau C, Watanabe T, Hammock BD (2004) Design, synthesis, and biological activity of 1, 3-disubstituted ureas as potent inhibitors of the soluble epoxide hydrolase of increased water solubility. J Med Chem 47:2110–2122. doi:10.1021/jm030514j PubMedGoogle Scholar
  96. Kim IH, Nishi K, Tsai HJ, Bradford T, Koda Y, Watanabe T, Morisseau C, Blanchfield J, Toth I, Hammock BD (2007) Design of bioavailable derivatives of 12-(3-adamantan-1-yl-ureido)dodecanoic acid, a potent inhibitor of the soluble epoxide hydrolase. Bioorg Med Chem 15:312–323. doi:10.1016/j.bmc.2006.09.057 PubMedGoogle Scholar
  97. Kiyohara C, Yoshimasu K, Takayama K, Nakanishi Y (2006) EPHX1 polymorphisms and the risk of lung cancer: a HuGE review. Epidemiology 17:89–99. doi:10.1097/01.ede.0000187627.70026.23 PubMedGoogle Scholar
  98. Knehr M, Thomas H, Arand M, Gebel T, Zeller HD, Oesch F (1993) Isolation and characterization of a cDNA encoding rat liver cytosolic epoxide hydrolase and its functional expression in Escherichia coli. J Biol Chem 268:17623–17627PubMedGoogle Scholar
  99. Kobayashi S, Kohda T, Miyoshi N, Kuroiwa Y, Aisaka K, Tsutsumi O, Kaneko-Ishino T, Ishino F (1997) Human PEG1/MEST, an imprinted gene on chromosome 7. Hum Mol Genet 6:781–786. doi:10.1093/hmg/6.5.781 PubMedGoogle Scholar
  100. Koerner IP, Jacks R, DeBarber AE, Koop D, Mao P, Grant DF, Alkayed NJ (2007) Polymorphisms in the human soluble epoxide hydrolase gene EPHX2 linked to neuronal survival after ischemic injury. J Neurosci 27:4642–4649. doi:10.1523/JNEUROSCI.0056-07.2007 PubMedGoogle Scholar
  101. Koonin EV, Tatusov RL (1994) Computer analysis of bacterial haloacid dehalogenases defines a large superfamily of hydrolases with diverse specificity. Application of an iterative approach to database search. J Mol Biol 244:125–132. doi:10.1006/jmbi.1994.1711 Google Scholar
  102. Krause RJ, Sharer JE, Elfarra AA (1997) Epoxide hydrolase-dependent metabolism of butadiene monoxide to 3-butene-1, 2-diol in mouse, rat, and human liver. Drug Metab Dispos 25:1013–1015PubMedGoogle Scholar
  103. Kwak MK, Itoh K, Yamamoto M, Sutter TR, Kensler TW (2001) Role of transcription factor Nrf2 in the induction of hepatic phase 2 and antioxidative enzymes in vivo by the cancer chemoprotective agent, 3H–1, 2-dimethiole-3-thione. Mol Med 7:135–145PubMedGoogle Scholar
  104. Lacourciere GM, Armstrong RN (1994) Microsomal and soluble epoxide hydrolases are members of the same family of C-X bond hydrolase enzymes. Chem Res Toxicol 7:121–124. doi:10.1021/tx00038a001 PubMedGoogle Scholar
  105. Lacourciere GM, Vakharia VN, Tan CP, Morris DI, Edwards GH, Moos M, Armstrong RN (1993) Interaction of hepatic microsomal epoxide hydrolase derived from a recombinant baculovirus expression system with an azarene oxide and an aziridine substrate analogue. Biochemistry 32:2610–2616. doi:10.1021/bi00061a019 PubMedGoogle Scholar
  106. Lahiri SD, Zhang G, Dai J, Dunaway-Mariano D, Allen KN (2004) Analysis of the substrate specificity loop of the HAD superfamily cap domain. Biochemistry 43:2812–2820. doi:10.1021/bi0356810 PubMedGoogle Scholar
  107. Lahiri SD, Zhang G, Dunaway-Mariano D, Allen KN (2006) Diversification of function in the haloacid dehalogenase enzyme superfamily: the role of the cap domain in hydrolytic phosphoruscarbon bond cleavage. Bioorg Chem 34:394–409. doi:10.1016/j.bioorg.2006.09.007 PubMedGoogle Scholar
  108. Laneuville O, Corey EJ, Couture R, Pace-Asciak CR (1991) Hepoxilin A3 (HxA3) is formed by the rat aorta and is metabolized into HxA3-C, a glutathione conjugate. Biochim Biophys Acta 1084:60–68PubMedGoogle Scholar
  109. Laughlin LT, Tzeng HF, Lin S, Armstrong RN (1998) Mechanism of microsomal epoxide hydrolase. Semifunctional site-specific mutants affecting the alkylation half-reaction. Biochemistry 37:2897–2904. doi:10.1021/bi972737f PubMedGoogle Scholar
  110. Lee WJ, Brennan P, Boffetta P, London SJ, Benhamou S, Rannug A, To-Figueras J, Ingelman-Sundberg M, Shields P, Gaspari L, Taioli E (2002) Microsomal epoxide hydrolase polymorphisms and lung cancer risk: a quantitative review. Biomarkers 7:230–241. doi:10.1080/13547500210121882 PubMedGoogle Scholar
  111. Lee CR, North KE, Bray MS, Fornage M, Seubert JM, Newman JW, Hammock BD, Couper DJ, Heiss G, Zeldin DC (2006) Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) study. Hum Mol Genet 15:1640–1649. doi:10.1093/hmg/ddl085 PubMedGoogle Scholar
  112. Lefebvre L, Viville S, Barton SC, Ishino F, Surani MA (1997) Genomic structure and parent-of-origin-specific methylation of Peg1. Hum Mol Genet 6:1907–1915. doi:10.1093/hmg/6.11.1907 PubMedGoogle Scholar
  113. Li PL, Campbell WB (1997) Epoxyeicosatrienoic acids activate K+ channels in coronary smooth muscle through a guanine nucleotide binding protein. Circ Res 80:877–884PubMedGoogle Scholar
  114. Li J, Carroll MA, Chander PN, Falck JR, Sangras B, Stier CT (2008) Soluble epoxide hydrolase inhibitor, AUDA, prevents early salt-sensitive hypertension. Front Biosci 13:3480–3487. doi:10.2741/2942 PubMedGoogle Scholar
  115. Lin TS, Huang HH, Fan YH, Chiou SH, Chow KC (2007) Genetic polymorphism and gene expression of microsomal epoxide hydrolase in non-small cell lung cancer. Oncol Rep 17:565–572PubMedGoogle Scholar
  116. Liu Y, Zhang Y, Schmelzer K, Lee TS, Fang X, Zhu Y, Spector AA, Gill S, Morisseau C, Hammock BD, Shyy JY (2005) The antiinflammatory effect of laminar flow: the role of PPARgamma, epoxyeicosatrienoic acids, and soluble epoxide hydrolase. Proc Natl Acad Sci USA 102:16747–16752. doi:10.1073/pnas.0508081102 PubMedGoogle Scholar
  117. Liu M, Sun A, Shin EJ, Liu X, Kim SG, Runyons CR, Markesbery W, Kim HC, Bing G (2006) Expression of microsomal epoxide hydrolase is elevated in Alzheimer’s hippocampus and induced by exogenous beta-amyloid and trimethyl-tin. Eur J Neurosci 23:2027–2034. doi:10.1111/j.1460-9568.2006.04724.x PubMedGoogle Scholar
  118. Liu M, Hunter R, Nguyen XV, Kim HC, Bing G (2008) Microsomal epoxide hydrolase deletion enhances tyrosine hydroxylase phosphorylation in mice after MPTP treatment. J Neurosci Res 86:2792–2801Google Scholar
  119. Lundgren B, Meijer J, DePierre JW (1987) Induction of cytosolic and microsomal epoxide hydrolases and proliferation of peroxisomes and mitochondria in mouse liver after dietary exposure to p-chlorophenoxyacetic acid, 2, 4-dichlorophenoxyacetic acid and 2, 4, 5-trichlorophenoxyacetic acid. Biochem Pharmacol 36:815–821. doi:10.1016/0006-2952(87)90169-9 PubMedGoogle Scholar
  120. Luo B, Norris C, Bolstad ES, Knecht DA, Grant DF (2008) Protein quaternary structure and expression levels contribute to peroxisomal-targeting-sequence-1-mediated peroxisomal import of human soluble epoxide hydrolase. J Mol Biol 380:31–41. doi:10.1016/j.jmb.2008.04.064 PubMedGoogle Scholar
  121. Luria A, Weldon SM, Kabcenell AK, Ingraham RH, Matera D, Jiang H, Gill R, Morisseau C, Newman JW, Hammock BD (2007) Compensatory mechanism for homeostatic blood pressure regulation in Ephx2 gene-disrupted mice. J Biol Chem 282:2891–2898. doi:10.1074/jbc.M608057200 PubMedGoogle Scholar
  122. McGee J, Fitzpatrick F (1985) Enzymatic hydration of leukotriene A4. Purification and characterization of a novel epoxide hydrolase from human erythrocytes. J Biol Chem 260:12832–12837Google Scholar
  123. McGlynn KA, Rosvold EA, Lustbader ED, Hu Y, Clapper ML, Zhou T, Wild CP, Xia XL, Baffoe-Bonnie A, Ofori-Adjei D et al (1995) Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin B1. Proc Natl Acad Sci USA 92:2384–2387. doi:10.1073/pnas.92.6.2384 PubMedGoogle Scholar
  124. McGlynn KA, Hunter K, LeVoyer T, Roush J, Wise P, Michielli RA, Shen FM, Evans AA, London WT, Buetow KH (2003) Susceptibility to aflatoxin B1-related primary hepatocellular carcinoma in mice and humans. Cancer Res 63:4594–4601PubMedGoogle Scholar
  125. Merrell MD, Augustine LM, Slitt AL, Cherrington NJ (2008) Induction of drug metabolism enzymes and transporters by oltipraz in rats. J Biochem Mol Toxicol 22:128–135. doi:10.1002/jbt.20225 PubMedGoogle Scholar
  126. Michaelis UR, Fisslthaler B, Barbosa-Sicard E, Falck JR, Fleming I, Busse R (2005) Cytochrome P450 epoxygenases 2C8 and 2C9 are implicated in hypoxia-induced endothelial cell migration and angiogenesis. J Cell Sci 118:5489–5498. doi:10.1242/jcs.02674 PubMedGoogle Scholar
  127. Minami M, Ohishi N, Mutoh H, Izumi T, Bito H, Wada H, Seyama Y, Toh H, Shimizu T (1990) Leukotriene A4 hydrolase is a zinc-containing aminopeptidase. Biochem Biophys Res Commun 173:620–626. doi:10.1016/S0006-291X(05)80080-4 PubMedGoogle Scholar
  128. Mittal RD, Srivastava DL (2007) Cytochrome P4501A1 and microsomal epoxide hydrolase gene polymorphisms: gene–environment interaction and risk of prostate cancer. DNA Cell Biol 26:791–798. doi:10.1089/dna.2007.0630 PubMedGoogle Scholar
  129. Miyata M, Kudo G, Lee YH, Yang TJ, Gelboin HV, Fernandez-Salguero P, Kimura S, Gonzalez FJ (1999) Targeted disruption of the microsomal epoxide hydrolase gene. Microsomal epoxide hydrolase is required for the carcinogenic activity of 7, 12-dimethylbenz[a]anthracene. J Biol Chem 274:23963–23968. doi:10.1074/jbc.274.34.23963 PubMedGoogle Scholar
  130. Moghaddam M, Motoba K, Borhan B, Pinot F, Hammock BD (1996) Novel metabolic pathways for linoleic and arachidonic acid metabolism. Biochim Biophys Acta 1290:327–339PubMedGoogle Scholar
  131. Monti J, Fischer J, Paskas S, Heinig M, Schulz H, Gosele C, Heuser A, Fischer R, Schmidt C, Schirdewan A, Gross V, Hummel O, Maatz H, Patone G, Saar K, Vingron M, Weldon SM, Lindpaintner K, Hammock BD, Rohde K, Dietz R, Cook SA, Schunck WH, Luft FC, Hubner N (2008) Soluble epoxide hydrolase is a susceptibility factor for heart failure in a rat model of human disease. Nat Genet 40:529–537. doi:10.1038/ng.129 PubMedGoogle Scholar
  132. Morais MC, Zhang W, Baker AS, Zhang G, Dunaway-Mariano D, Allen KN (2000) The crystal structure of bacillus cereus phosphonoacetaldehyde hydrolase: insight into catalysis of phosphorus bond cleavage and catalytic diversification within the HAD enzyme superfamily. Biochemistry 39:10385–10396. doi:10.1021/bi001171j PubMedGoogle Scholar
  133. Morisseau C, Hammock BD (2005) Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles. Annu Rev Pharmacol Toxicol 45:311–333. doi:10.1146/annurev.pharmtox.45.120403.095920 PubMedGoogle Scholar
  134. Morisseau C, Du G, Newman JW, Hammock BD (1998) Mechanism of mammalian soluble epoxide hydrolase inhibition by chalcone oxide derivatives. Arch Biochem Biophys 356:214–228. doi:10.1006/abbi.1998.0756 PubMedGoogle Scholar
  135. Morisseau C, Newman JW, Dowdy DL, Goodrow MH, Hammock BD (2001) Inhibition of microsomal epoxide hydrolases by ureas, amides, and amines. Chem Res Toxicol 14:409–415. doi:10.1021/tx0001732 PubMedGoogle Scholar
  136. Morisseau C, Goodrow MH, Newman JW, Wheelock CE, Dowdy DL, Hammock BD (2002) Structural refinement of inhibitors of urea-based soluble epoxide hydrolases. Biochem Pharmacol 63:1599–1608. doi:10.1016/S0006-2952(02)00952-8 PubMedGoogle Scholar
  137. Morisseau C, Newman JW, Tsai HJ, Baecker PA, Hammock BD (2006) Peptidyl-urea based inhibitors of soluble epoxide hydrolases. Bioorg Med Chem Lett 16:5439–5444. doi:10.1016/j.bmcl.2006.07.073 PubMedGoogle Scholar
  138. Morisseau C, Newman JW, Wheelock CE, Hill Iii T, Morin D, Buckpitt AR, Hammock BD (2008) Development of metabolically stable inhibitors of Mammalian microsomal epoxide hydrolase. Chem Res Toxicol 21:951–957. doi:10.1021/tx700446u PubMedGoogle Scholar
  139. Mowbray SL, Elfstrom LT, Ahlgren KM, Andersson CE, Widersten M (2006) X-ray structure of potato epoxide hydrolase sheds light on substrate specificity in plant enzymes. Protein Sci 15:1628–1637. doi:10.1110/ps.051792106 PubMedGoogle Scholar
  140. Mrsny RJ, Gewirtz AT, Siccardi D, Savidge T, Hurley BP, Madara JL, McCormick BA (2004) Identification of hepoxilin A3 in inflammatory events: a required role in neutrophil migration across intestinal epithelia. Proc Natl Acad Sci USA 101:7421–7426. doi:10.1073/pnas.0400832101 PubMedGoogle Scholar
  141. Mullen RT, Trelease RN, Duerk H, Arand M, Hammock BD, Oesch F, Grant DF (1999) Differential subcellular localization of endogenous and transfected soluble epoxide hydrolase in mammalian cells: evidence for isozyme variants. FEBS Lett 445:301–305. doi:10.1016/S0014-5793(99)00142-8 PubMedGoogle Scholar
  142. Muller F, Arand M, Frank H, Seidel A, Hinz W, Winkler L, Hanel K, Blee E, Beetham JK, Hammock BD, Oesch F (1997) Visualization of a covalent intermediate between microsomal epoxide hydrolase, but not cholesterol epoxide hydrolase, and their substrates. Eur J Biochem 245:490–496. doi:10.1111/j.1432-1033.1997.00490.x PubMedGoogle Scholar
  143. Nakanishi H, Suda T, Katoh M, Watanabe A, Igishi T, Kodani M, Matsumoto S, Nakamoto M, Shigeoka Y, Okabe T, Oshimura M, Shimizu E (2004) Loss of imprinting of PEG1/MEST in lung cancer cell lines. Oncol Rep 12:1273–1278PubMedGoogle Scholar
  144. Nardini M, Ridder IS, Rozeboom HJ, Kalk KH, Rink R, Janssen DB, Dijkstra BW (1999) The x-ray structure of epoxide hydrolase from Agrobacterium radiobacter AD1. An enzyme to detoxify harmful epoxides. J Biol Chem 274:14579–14586. doi:10.1074/jbc.274.21.14579 PubMedGoogle Scholar
  145. Newman JW, Morisseau C, Harris TR, Hammock BD (2003) The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity. Proc Natl Acad Sci USA 100:1558–1563. doi:10.1073/pnas.0437724100 PubMedGoogle Scholar
  146. Newman JW, Morisseau C, Hammock BD (2005) Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog Lipid Res 44:1–51. doi:10.1016/j.plipres.2004.10.001 PubMedGoogle Scholar
  147. Nigam S, Zafiriou MP, Deva R, Ciccoli R, Roux-Van der Merwe R (2007) Structure, biochemistry and biology of hepoxilins: an update. FEBS J 274:3503–3512. doi:10.1111/j.1742-4658.2007.05910.x PubMedGoogle Scholar
  148. Nikonova L, Koza RA, Mendoza T, Chao PM, Curley JP, Kozak LP (2008) Mesoderm-specific transcript is associated with fat mass expansion in response to a positive energy balance. FASEB J 22:3925–3937. doi:10.1096/fj.08-108266 PubMedGoogle Scholar
  149. Oesch F (1973) Mammalian epoxide hydrolases: inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds. Xenobiotica 3:305–340PubMedCrossRefGoogle Scholar
  150. Oesch F (1974) Purification and specificity of a human microsomal epoxide hydratase. Biochem J 139:77–88PubMedGoogle Scholar
  151. Oesch F, Timms CW, Walker CH, Guenthner TM, Sparrow A, Watabe T, Wolf CR (1984) Existence of multiple forms of microsomal epoxide hydrolases with radically different substrate specificities. Carcinogenesis 5:7–9. doi:10.1093/carcin/5.1.7 PubMedGoogle Scholar
  152. Oesch F, Schladt L, Hartmann R, Timms C, Worner W (1986) Rat cytosolic epoxide hydrolase. Adv Exp Med Biol 197:195–201PubMedGoogle Scholar
  153. Oesch F, Herrero ME, Hengstler JG, Lohmann M, Arand M (2000) Metabolic detoxification: implications for thresholds. Toxicol Pathol 28:382–387. doi:10.1177/019262330002800305 PubMedGoogle Scholar
  154. Ohtoshi K, Kaneto H, Node K, Nakamura Y, Shiraiwa T, Matsuhisa M, Yamasaki Y (2005) Association of soluble epoxide hydrolase gene polymorphism with insulin resistance in type 2 diabetic patients. Biochem Biophys Res Commun 331:347–350. doi:10.1016/j.bbrc.2005.03.171 PubMedGoogle Scholar
  155. Oliw EH, Guengerich FP, Oates JA (1982) Oxygenation of arachidonic acid by hepatic monooxygenases. Isolation and metabolism of four epoxide intermediates. J Biol Chem 257:3771–3781PubMedGoogle Scholar
  156. Omiecinski CJ, Hassett C, Hosagrahara V (2000) Epoxide hydrolase—polymorphism and role in toxicology. Toxicol Lett 112–113:365–370. doi:10.1016/S0378-4274(99)00235-0 PubMedGoogle Scholar
  157. Pace-Asciak CR, Lee WS (1989) Purification of hepoxilin epoxide hydrolase from rat liver. J Biol Chem 264:9310–9313PubMedGoogle Scholar
  158. Pace-Asciak CR, Martin JM (1984) Hepoxilin, a new family of insulin secretagogues formed by intact rat pancreatic islets. Prostaglandins Leukot Med 16:173–180. doi:10.1016/0262-1746(84)90069-6 PubMedGoogle Scholar
  159. Pace-Asciak CR, Laneuville O, Su WG, Corey EJ, Gurevich N, Wu P, Carlen PL (1990) A glutathione conjugate of hepoxilin A3: formation and action in the rat central nervous system. Proc Natl Acad Sci USA 87:3037–3041. doi:10.1073/pnas.87.8.3037 PubMedGoogle Scholar
  160. Pace-Asciak CR, Reynaud D, Demin PM (1995) Hepoxilins: a review on their enzymatic formation, metabolism and chemical synthesis. Lipids 30:107–114. doi:10.1007/BF02538262 PubMedGoogle Scholar
  161. Papadopoulos D, Seidegard J, Georgellis A, Rydstrom J (1985) Subcellular distribution, catalytic properties and partial purification of epoxide hydrolase in the human adrenal gland. Chem Biol Interact 55:249–260. doi:10.1016/S0009-2797(85)80133-2 PubMedGoogle Scholar
  162. Pedersen IS, Dervan PA, Broderick D, Harrison M, Miller N, Delany E, O’Shea D, Costello P, McGoldrick A, Keating G, Tobin B, Gorey T, McCann A (1999) Frequent loss of imprinting of PEG1/MEST in invasive breast cancer. Cancer Res 59:5449–5451PubMedGoogle Scholar
  163. Pinot F, Grant DF, Beetham JK, Parker AG, Borhan B, Landt S, Jones AD, Hammock BD (1995) Molecular and biochemical evidence for the involvement of the Asp-333-His-523 pair in the catalytic mechanism of soluble epoxide hydrolase. J Biol Chem 270:7968–7974. doi:10.1074/jbc.270.14.7968 PubMedGoogle Scholar
  164. Pomposiello SI, Quilley J, Carroll MA, Falck JR, McGiff JC (2003) 5, 6-Epoxyeicosatrienoic acid mediates the enhanced renal vasodilation to arachidonic acid in the SHR. Hypertension 42:548–554. doi:10.1161/01.HYP.0000090095.87899.36 PubMedGoogle Scholar
  165. Potente M, Fisslthaler B, Busse R, Fleming I (2003) 11, 12-Epoxyeicosatrienoic acid-induced inhibition of FOXO factors promotes endothelial proliferation by down-regulating p27Kip1. J Biol Chem 278:29619–29625. doi:10.1074/jbc.M305385200 PubMedGoogle Scholar
  166. Prestwich GD, Lucarelli I, Park SK, Loury DN, Moody DE, Hammock BD (1985) Cyclopropyl oxiranes: reversible inhibitors of cytosolic and microsomal epoxide hydrolases. Arch Biochem Biophys 237:361–372. doi:10.1016/0003-9861(85)90288-7 PubMedGoogle Scholar
  167. Przybyla-Zawislak BD, Srivastava PK, Vazquez-Matias J, Mohrenweiser HW, Maxwell JE, Hammock BD, Bradbury JA, Enayetallah AE, Zeldin DC, Grant DF (2003) Polymorphisms in human soluble epoxide hydrolase. Mol Pharmacol 64:482–490. doi:10.1124/mol.64.2.482 PubMedGoogle Scholar
  168. Raaka S, Hassett C, Omiencinski CJ (1998) Human microsomal epoxide hydrolase: 5′-flanking region genetic polymorphisms. Carcinogenesis 19:387–393. doi:10.1093/carcin/19.3.387 PubMedGoogle Scholar
  169. Radmark O, Shimizu T, Jornvall H, Samuelsson B (1984) Leukotriene A4 hydrolase in human leukocytes. Purification and properties. J Biol Chem 259:12339–12345PubMedGoogle Scholar
  170. Rappaport SM, Yeowell-O’Connell K, Bodell W, Yager JW, Symanski E (1996) An investigation of multiple biomarkers among workers exposed to styrene and styrene-7, 8-oxide. Cancer Res 56:5410–5416PubMedGoogle Scholar
  171. Recio L, Bauer A, Faiola B (2005) Use of genetically modified mouse models to assess pathways of benzene-induced bone marrow cytotoxicity and genotoxicity. Chem Biol Interact 153–154:159–164. doi:10.1016/j.cbi.2005.03.020 PubMedGoogle Scholar
  172. Reddy BS, Wynder EL (1977) Metabolic epidemiology of colon cancer. Fecal bile acids and neutral sterols in colon cancer patients and patients with adenomatous polyps. Cancer 39:2533–2539. doi:10.1002/1097-0142(197706)39:6<2533::AID-CNCR2820390634>3.0.CO;2-X PubMedGoogle Scholar
  173. Reynaud D, Demin PM, Sutherland M, Nigam S, Pace-Asciak CR (1999) Hepoxilin signaling in intact human neutrophils: biphasic elevation of intracellular calcium by unesterified hepoxilin A3. FEBS Lett 446:236–238. doi:10.1016/S0014-5793(99)00225-2 PubMedGoogle Scholar
  174. Rigsby RE, Fillgrove KL, Beihoffer LA, Armstrong RN (2005) Fosfomycin resistance proteins: a nexus of glutathione transferases and epoxide hydrolases in a metalloenzyme superfamily. Methods Enzymol 401:367–379. doi:10.1016/S0076-6879(05)01023-2 PubMedGoogle Scholar
  175. Rimner A, Al Makdessi S, Sweidan H, Wischhusen J, Rabenstein B, Shatat K, Mayer P, Spyridopoulos I (2005) Relevance and mechanism of oxysterol stereospecificity in coronary artery disease. Free Radic Biol Med 38:535–544. doi:10.1016/j.freeradbiomed.2004.11.016 PubMedGoogle Scholar
  176. Ryan L, O’Callaghan YC, O’Brien NM (2004) Comparison of the apoptotic processes induced by the oxysterols 7beta-hydroxycholesterol and cholesterol-5beta, 6beta-epoxide. Cell Biol Toxicol 20:313–323. doi:10.1007/s10565-004-5066-7 PubMedGoogle Scholar
  177. Saito S, Iida A, Sekine A, Eguchi C, Miura Y, Nakamura Y (2001) Seventy genetic variations in human microsomal and soluble epoxide hydrolase genes (EPHX1 and EPHX2) in the Japanese population. J Hum Genet 46:325–329. doi:10.1007/s100380170067 PubMedGoogle Scholar
  178. Sandberg M, Meijer J (1996) Structural characterization of the human soluble epoxide hydrolase gene (EPHX2). Biochem Biophys Res Commun 221:333–339. doi:10.1006/bbrc.1996.0596 PubMedGoogle Scholar
  179. Sandberg M, Hassett C, Adman ET, Meijer J, Omiecinski CJ (2000) Identification and functional characterization of human soluble epoxide hydrolase genetic polymorphisms. J Biol Chem 275:28873–28881. doi:10.1074/jbc.M001153200 PubMedGoogle Scholar
  180. Sato K, Emi M, Ezura Y, Fujita Y, Takada D, Ishigami T, Umemura S, Xin Y, Wu LL, Larrinaga-Shum S, Stephenson SH, Hunt SC, Hopkins PN (2004) Soluble epoxide hydrolase variant (Glu287Arg) modifies plasma total cholesterol and triglyceride phenotype in familial hypercholesterolemia: intrafamilial association study in an eight-generation hyperlipidemic kindred. J Hum Genet 49:29–34. doi:10.1007/s10038-003-0103-6 PubMedGoogle Scholar
  181. Schmelzer KR, Kubala L, Newman JW, Kim IH, Eiserich JP, Hammock BD (2005) Soluble epoxide hydrolase is a therapeutic target for acute inflammation. Proc Natl Acad Sci USA 102:9772–9777. doi:10.1073/pnas.0503279102 PubMedGoogle Scholar
  182. Schmelzer KR, Inceoglu B, Kubala L, Kim IH, Jinks SL, Eiserich JP, Hammock BD (2006) Enhancement of antinociception by coadministration of nonsteroidal anti-inflammatory drugs and soluble epoxide hydrolase inhibitors. Proc Natl Acad Sci USA 103:13646–13651. doi:10.1073/pnas.0605908103 PubMedGoogle Scholar
  183. Selengut JD (2001) MDP-1 is a new and distinct member of the haloacid dehalogenase family of aspartate-dependent phosphohydrolases. Biochemistry 40:12704–12711. doi:10.1021/bi011405e PubMedGoogle Scholar
  184. Sevanian A, Peterson AR (1984) Cholesterol epoxide is a direct-acting mutagen. Proc Natl Acad Sci USA 81:4198–4202. doi:10.1073/pnas.81.13.4198 PubMedGoogle Scholar
  185. Sevanian A, Peterson AR (1986) The cytotoxic and mutagenic properties of cholesterol oxidation products. Food Chem Toxicol 24:1103–1110. doi:10.1016/0278-6915(86)90295-4 PubMedGoogle Scholar
  186. Shimada T (2006) Xenobiotic-metabolizing enzymes involved in activation and detoxification of carcinogenic polycyclic aromatic hydrocarbons. Drug Metab Pharmacokinet 21:257–276. doi:10.2133/dmpk.21.257 PubMedGoogle Scholar
  187. Shkolnik K, Ben-Dor S, Galiani D, Hourvitz A, Dekel N (2007) A novel ovary-specific and ovulation-associated variant of epoxide hydrolase 2. FEBS Lett 581:4891–4898. doi:10.1016/j.febslet.2007.09.016 PubMedGoogle Scholar
  188. Shou M, Gonzalez FJ, Gelboin HV (1996) Stereoselective epoxidation and hydration at the K-region of polycyclic aromatic hydrocarbons by cDNA-expressed cytochromes P450 1A1, 1A2, and epoxide hydrolase. Biochemistry 35:15807–15813. doi:10.1021/bi962042z PubMedGoogle Scholar
  189. Sinal CJ, Miyata M, Tohkin M, Nagata K, Bend JR, Gonzalez FJ (2000) Targeted disruption of soluble epoxide hydrolase reveals a role in blood pressure regulation. J Biol Chem 275:40504–40510. doi:10.1074/jbc.M008106200 PubMedGoogle Scholar
  190. Smit MS (2004) Fungal epoxide hydrolases: new landmarks in sequence-activity space. Trends Biotechnol 22:123–129. doi:10.1016/j.tibtech.2004.01.012 PubMedGoogle Scholar
  191. Smith CA, Harrison DJ (1997) Association between polymorphism in gene for microsomal epoxide hydrolase and susceptibility to emphysema. Lancet 350:630–633. doi:10.1016/S0140-6736(96)08061-0 PubMedGoogle Scholar
  192. Smith KR, Pinkerton KE, Watanabe T, Pedersen TL, Ma SJ, Hammock BD (2005) Attenuation of tobacco smoke-induced lung inflammation by treatment with a soluble epoxide hydrolase inhibitor. Proc Natl Acad Sci USA 102:2186–2191. doi:10.1073/pnas.0409591102 PubMedGoogle Scholar
  193. Snider NT, Kornilov AM, Kent UM, Hollenberg PF (2007) Anandamide metabolism by human liver and kidney microsomal cytochrome p450 enzymes to form hydroxyeicosatetraenoic and epoxyeicosatrienoic acid ethanolamides. J Pharmacol Exp Ther 321:590–597. doi:10.1124/jpet.107.119321 PubMedGoogle Scholar
  194. Snyder R, Chepiga T, Yang CS, Thomas H, Platt K, Oesch F (1993) Benzene metabolism by reconstituted cytochromes P450 2B1 and 2E1 and its modulation by cytochrome b5, microsomal epoxide hydrolase, and glutathione transferases: evidence for an important role of microsomal epoxide hydrolase in the formation of hydroquinone. Toxicol Appl Pharmacol 122:172–181. doi:10.1006/taap.1993.1185 PubMedGoogle Scholar
  195. Spector AA, Norris AW (2007) Action of epoxyeicosatrienoic acids on cellular function. Am J Physiol Cell Physiol 292:C996–C1012. doi:10.1152/ajpcell.00402.2006 PubMedGoogle Scholar
  196. Srivastava PK, Sharma VK, Kalonia DS, Grant DF (2004) Polymorphisms in human soluble epoxide hydrolase: effects on enzyme activity, enzyme stability, and quaternary structure. Arch Biochem Biophys 427:164–169. doi:10.1016/j.abb.2004.05.003 PubMedGoogle Scholar
  197. Stansberg C, Vik-Mo AO, Holdhus R, Breilid H, Srebro B, Petersen K, Jorgensen HA, Jonassen I, Steen VM (2007) Gene expression profiles in rat brain disclose CNS signature genes and regional patterns of functional specialisation. BMC Genomics 8:94. doi:10.1186/1471-2164-8-94 PubMedGoogle Scholar
  198. Summerer S, Hanano A, Utsumi S, Arand M, Schuber F, Blee E (2002) Stereochemical features of the hydrolysis of 9, 10-epoxystearic acid catalysed by plant and mammalian epoxide hydrolases. Biochem J 366:471–480. doi:10.1042/BJ20011778 PubMedGoogle Scholar
  199. Sumner SJ, Fennell TR (1994) Review of the metabolic fate of styrene. Crit Rev Toxicol 24(1):S11–S33. doi:10.3109/10408449409020138 PubMedGoogle Scholar
  200. Sun J, Sui X, Bradbury JA, Zeldin DC, Conte MS, Liao JK (2002) Inhibition of vascular smooth muscle cell migration by cytochrome p450 epoxygenase-derived eicosanoids. Circ Res 90:1020–1027. doi:10.1161/01.RES.0000017727.35930.33 PubMedGoogle Scholar
  201. Sun Z, Sood S, Li N, Ramji D, Yang P, Newman RA, Yang CS, Chen X (2006) Involvement of the 5-lipoxygenase/leukotriene A4 hydrolase pathway in 7, 12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch, and inhibition of carcinogenesis by its inhibitors. Carcinogenesis 27:1902–1908. doi:10.1093/carcin/bgl039 PubMedGoogle Scholar
  202. Sura P, Sura R, Enayetallah AE, Grant DF (2008) Distribution and expression of soluble epoxide hydrolase in human brain. J Histochem Cytochem 56:551–559. doi:10.1369/jhc.2008.950659 PubMedGoogle Scholar
  203. Terashvili M, Tseng LF, Wu HE, Narayanan J, Hart LM, Falck JR, Pratt PF, Harder DR (2008) Antinociception produced by 14,15-epoxyeicosatrienoic acid is mediated by the activation of {beta}-endorphin and Met-enkephalin in the rat ventrolateral periaqueductal gray. J Pharmacol Exp Ther 326:614–622Google Scholar
  204. Thunnissen MM, Nordlund P, Haeggstrom JZ (2001) Crystal structure of human leukotriene A(4) hydrolase, a bifunctional enzyme in inflammation. Nat Struct Biol 8:131–135. doi:10.1038/84117 PubMedGoogle Scholar
  205. Toulza E, Mattiuzzo NR, Galliano MF, Jonca N, Dossat C, Jacob D, de Daruvar A, Wincker P, Serre G, Guerrin M (2007) Large-scale identification of human genes implicated in epidermal barrier function. Genome Biol 8:R107. doi:10.1186/gb-2007-8-6-r107 PubMedGoogle Scholar
  206. Tran KL, Aronov PA, Tanaka H, Newman JW, Hammock BD, Morisseau C (2005) Lipid sulfates and sulfonates are allosteric competitive inhibitors of the N-terminal phosphatase activity of the mammalian soluble epoxide hydrolase. Biochemistry 44:12179–12187. doi:10.1021/bi050842g PubMedGoogle Scholar
  207. Tranah GJ, Chan AT, Giovannucci E, Ma J, Fuchs C, Hunter DJ (2005) Epoxide hydrolase and CYP2C9 polymorphisms, cigarette smoking, and risk of colorectal carcinoma in the Nurses’ Health Study and the Physicians’ Health Study. Mol Carcinog 44:21–30. doi:10.1002/mc.20112 PubMedGoogle Scholar
  208. Tsuge H, Ago H, Aoki M, Furuno M, Noma M, Miyano M, Minami M, Izumi T, Shimizu T (1994) Crystallization and preliminary X-ray crystallographic studies of recombinant human leukotriene A4 hydrolase complexed with bestatin. J Mol Biol 238:854–856. doi:10.1006/jmbi.1994.1341 PubMedGoogle Scholar
  209. Tzeng HF, Laughlin LT, Armstrong RN (1998) Semifunctional site-specific mutants affecting the hydrolytic half-reaction of microsomal epoxide hydrolase. Biochemistry 37:2905–2911. doi:10.1021/bi9727388 PubMedGoogle Scholar
  210. van Bladeren PJ, Sayer JM, Ryan DE, Thomas PE, Levin W, Jerina DM (1985) Differential stereoselectivity of cytochromes P-450b and P-450c in the formation of naphthalene and anthracene 1, 2-oxides. The role of epoxide hydrolase in determining the enantiomer composition of the 1, 2-dihydrodiols formed. J Biol Chem 260:10226–10235PubMedGoogle Scholar
  211. van der Werf MJ, Overkamp KM, de Bont JA (1998) Limonene-1, 2-epoxide hydrolase from Rhodococcus erythropolis DCL14 belongs to a novel class of epoxide hydrolases. J Bacteriol 180:5052–5057PubMedGoogle Scholar
  212. van Loo B, Kingma J, Arand M, Wubbolts MG, Janssen DB (2006) Diversity and biocatalytic potential of epoxide hydrolases identified by genome analysis. Appl Environ Microbiol 72:2905–2917. doi:10.1128/AEM.72.4.2905-2917.2006 PubMedGoogle Scholar
  213. Vejux A, Kahn E, Menetrier F, Montange T, Lherminier J, Riedinger JM, Lizard G (2007) Cytotoxic oxysterols induce caspase-independent myelin figure formation and caspase-dependent polar lipid accumulation. Histochem Cell Biol 127:609–624. doi:10.1007/s00418-006-0268-0 PubMedGoogle Scholar
  214. von Dippe P, Zhu QS, Levy D (2003) Cell surface expression and bile acid transport function of one topological form of m-epoxide hydrolase. Biochem Biophys Res Commun 309:804–809. doi:10.1016/j.bbrc.2003.08.074 Google Scholar
  215. Wang W, Kim R, Jancarik J, Yokota H, Kim SH (2001) Crystal structure of phosphoserine phosphatase from Methanococcus jannaschii, a hyperthermophile, at 1.8 A resolution. Structure 9:65–71. doi:10.1016/S0969-2126(00)00558-X PubMedGoogle Scholar
  216. Wang W, Cho HS, Kim R, Jancarik J, Yokota H, Nguyen HH, Grigoriev IV, Wemmer DE, Kim SH (2002) Structural characterization of the reaction pathway in phosphoserine phosphatase: crystallographic “snapshots” of intermediate states. J Mol Biol 319:421–431. doi:10.1016/S0022-2836(02)00324-8 PubMedGoogle Scholar
  217. Watabe T, Kanai M, Isobe M, Ozawa N (1981) The hepatic microsomal biotransformation of delta 5-steroids to 5 alpha, 6 beta-glycols via alpha- and beta-epoxides. J Biol Chem 256:2900–2907PubMedGoogle Scholar
  218. Watabe T, Ozawa N, Ishii H, Chiba K, Hiratsuka A (1986) Hepatic microsomal cholesterol epoxide hydrolase: selective inhibition by detergents and separation from xenobiotic epoxide hydrolase. Biochem Biophys Res Commun 140:632–637. doi:10.1016/0006-291X(86)90778-3 PubMedGoogle Scholar
  219. Wickliffe JK, Herring SM, Hallberg LM, Galbert LA, Masters OEIII, Ammenheuser MM, Xie J, Friedberg EC, Lloyd RS, Abdel-Rahman SZ, Ward JB Jr (2007) Detoxification of olefinic epoxides and nucleotide excision repair of epoxide-mediated DNA damage: Insights from animal models examining human sensitivity to 1, 3-butadiene. Chem Biol Interact 166:226–231. doi:10.1016/j.cbi.2006.04.017 PubMedGoogle Scholar
  220. Wild CP, Yin F, Turner PC, Chemin I, Chapot B, Mendy M, Whittle H, Kirk GD, Hall AJ (2000) Environmental and genetic determinants of aflatoxin-albumin adducts in the Gambia. Int J Cancer 86:1–7. doi:10.1002/(SICI)1097-0215(20000401)86:1<1::AID-IJC1>3.0.CO;2-I PubMedGoogle Scholar
  221. Wilson AM, Sisk RM, O’Brien NM (1997) Modulation of cholestane-3 beta, 5 alpha, 6 beta-triol toxicity by butylated hydroxytoluene, alpha-tocopherol and beta-carotene in newborn rat kidney cells in vitro. Br J Nutr 78:479–492. doi:10.1079/BJN19970165 PubMedGoogle Scholar
  222. Yamashita S, Tsujino Y, Moriguchi K, Tatematsu M, Ushijima T (2006) Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2′-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci 97:64–71. doi:10.1111/j.1349-7006.2006.00136.x PubMedGoogle Scholar
  223. Yu Z, Schneider C, Boeglin WE, Brash AR (2007) Epidermal lipoxygenase products of the hepoxilin pathway selectively activate the nuclear receptor PPARalpha. Lipids 42:491–497. doi:10.1007/s11745-007-3054-4 PubMedGoogle Scholar
  224. Zeldin DC, Kobayashi J, Falck JR, Winder BS, Hammock BD, Snapper JR, Capdevila JH (1993) Regio- and enantiofacial selectivity of epoxyeicosatrienoic acid hydration by cytosolic epoxide hydrolase. J Biol Chem 268:6402–6407PubMedGoogle Scholar
  225. Zeldin DC, Moomaw CR, Jesse N, Tomer KB, Beetham J, Hammock BD, Wu S (1996) Biochemical characterization of the human liver cytochrome P450 arachidonic acid epoxygenase pathway. Arch Biochem Biophys 330:87–96. doi:10.1006/abbi.1996.0229 PubMedGoogle Scholar
  226. Zhang W, Koerner IP, Noppens R, Grafe M, Tsai HJ, Morisseau C, Luria A, Hammock BD, Falck JR, Alkayed NJ (2007) Soluble epoxide hydrolase: a novel therapeutic target in stroke. J Cereb Blood Flow Metab 27:1931–1940. doi:10.1038/sj.jcbfm.9600494 PubMedGoogle Scholar
  227. Zhang L, Ding H, Yan J, Hui R, Wang W, Kissling GE, Zeldin DC, Wang DW (2008a) Genetic variation in cytochrome P450 2J2 and soluble epoxide hydrolase and risk of ischemic stroke in a Chinese population. Pharmacogenet Genomics 18:45–51. doi:10.1097/FPC.0b013e3282f313e8 PubMedGoogle Scholar
  228. Zhang W, Otsuka T, Sugo N, Ardeshiri A, Alhadid YK, Iliff JJ, DeBarber AE, Koop DR, Alkayed NJ (2008b) Soluble epoxide hydrolase gene deletion is protective against experimental cerebral ischemia. Stroke 39:2073–2078. doi:10.1161/STROKEAHA.107.508325 PubMedGoogle Scholar
  229. Zhao X, Yamamoto T, Newman JW, Kim IH, Watanabe T, Hammock BD, Stewart J, Pollock JS, Pollock DM, Imig JD (2004) Soluble epoxide hydrolase inhibition protects the kidney from hypertension-induced damage. J Am Soc Nephrol 15:1244–1253PubMedGoogle Scholar
  230. Zhou GX, Ding XL, Huang JF, Zhang H, Wu SB (2007) Suppression of 5-lipoxygenase gene is involved in triptolide-induced apoptosis in pancreatic tumor cell lines. Biochim Biophys Acta 1770:1021–1027PubMedGoogle Scholar
  231. Zhu QS, Qian B, Levy D (2004) Regulation of human microsomal epoxide hydrolase gene (EPHX1) expression by the transcription factor GATA-4. Biochim Biophys Acta 1676:251–260PubMedGoogle Scholar
  232. Zou J, Hallberg BM, Bergfors T, Oesch F, Arand M, Mowbray SL, Jones TA (2000) Structure of Aspergillus niger epoxide hydrolase at 1.8 A resolution: implications for the structure and function of the mammalian microsomal class of epoxide hydrolases. Structure 8:111–122. doi:10.1016/S0969-2126(00)00087-3 PubMedGoogle Scholar
  233. Zusterzeel PL, Peters WH, Visser W, Hermsen KJ, Roelofs HM, Steegers EA (2001) A polymorphism in the gene for microsomal epoxide hydrolase is associated with pre-eclampsia. J Med Genet 38:234–237. doi:10.1136/jmg.38.4.234 PubMedGoogle Scholar

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© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Institute of Pharmacology and ToxicologyUniversity of ZürichZurichSwitzerland

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