Ephx2

Summary

Gene Symbol: Ephx2
Description: epoxide hydrolase 2, cytoplasmic
Alias: CEH, Eph2, SEH, sEP, bifunctional epoxide hydrolase 2, cytosolic epoxide hydrolase, epoxide hydratase, epoxide hydrolase 2C, soluble epoxide hydrolase
Species: mouse
Products:     Ephx2

Top Publications

  1. Luria A, Bettaieb A, Xi Y, Shieh G, Liu H, Inoue H, et al. Soluble epoxide hydrolase deficiency alters pancreatic islet size and improves glucose homeostasis in a model of insulin resistance. Proc Natl Acad Sci U S A. 2011;108:9038-43 pubmed publisher
    ..The availability of EETs is limited primarily by the soluble epoxide hydrolase (sEH, EPHX2), which metabolizes EETs to their less active diols...
  2. Bettaieb A, Nagata N, Aboubechara D, Chahed S, Morisseau C, Hammock B, et al. Soluble epoxide hydrolase deficiency or inhibition attenuates diet-induced endoplasmic reticulum stress in liver and adipose tissue. J Biol Chem. 2013;288:14189-99 pubmed publisher
    b>Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose inhibition has beneficial effects in cardiovascular, inflammatory, and metabolic diseases in murine models...
  3. Hou H, Hammock B, Su K, Morisseau C, Kou Y, Imaoka S, et al. N-terminal domain of soluble epoxide hydrolase negatively regulates the VEGF-mediated activation of endothelial nitric oxide synthase. Cardiovasc Res. 2012;93:120-9 pubmed publisher
    The mammalian soluble epoxide hydrolase (sEH) has both an epoxide hydrolase and a phosphatase domain...
  4. Manhiani M, Quigley J, Knight S, Tasoobshirazi S, Moore T, Brands M, et al. Soluble epoxide hydrolase gene deletion attenuates renal injury and inflammation with DOCA-salt hypertension. Am J Physiol Renal Physiol. 2009;297:F740-8 pubmed publisher
    Inhibition of soluble epoxide hydrolase (sEH) has been shown to be renal protective in rat models of salt-sensitive hypertension...
  5. Morisseau C, Schebb N, Dong H, Ulu A, Aronov P, Hammock B. Role of soluble epoxide hydrolase phosphatase activity in the metabolism of lysophosphatidic acids. Biochem Biophys Res Commun. 2012;419:796-800 pubmed publisher
    The EPXH2 gene encodes for the soluble epoxide hydrolase (sEH), which has two distinct enzyme activities: epoxide hydrolase (Cterm-EH) and phosphatase (Nterm-phos)...
  6. Luria A, Morisseau C, Tsai H, Yang J, Inceoglu B, De Taeye B, et al. Alteration in plasma testosterone levels in male mice lacking soluble epoxide hydrolase. Am J Physiol Endocrinol Metab. 2009;297:E375-83 pubmed publisher
    b>Soluble epoxide hydrolase (Ephx2, sEH) is a bifunctional enzyme with COOH-terminal hydrolase and NH(2)-terminal phosphatase activities...
  7. Enayetallah A, Luria A, Luo B, Tsai H, Sura P, Hammock B, et al. Opposite regulation of cholesterol levels by the phosphatase and hydrolase domains of soluble epoxide hydrolase. J Biol Chem. 2008;283:36592-8 pubmed publisher
    b>Soluble epoxide hydrolase (sEH) is a bifunctional enzyme with two catalytic domains: a C-terminal epoxide hydrolase domain and an N-terminal phosphatase domain...
  8. Sirish P, Li N, Liu J, Lee K, Hwang S, Qiu H, et al. Unique mechanistic insights into the beneficial effects of soluble epoxide hydrolase inhibitors in the prevention of cardiac fibrosis. Proc Natl Acad Sci U S A. 2013;110:5618-23 pubmed publisher
    ..We have previously demonstrated the beneficial effects of several potent soluble epoxide hydrolase inhibitors (sEHIs) in different models of cardiac hypertrophy and failure...
  9. Zhang W, Otsuka T, Sugo N, Ardeshiri A, Alhadid Y, Iliff J, et al. Soluble epoxide hydrolase gene deletion is protective against experimental cerebral ischemia. Stroke. 2008;39:2073-8 pubmed publisher
    ..However, EETs are rapidly metabolized via soluble epoxide hydrolase (sEH) to dihydroxyeicosatrienoic acids (DHETs)...

More Information

Publications82

  1. Luria A, Weldon S, Kabcenell A, Ingraham R, Matera D, Jiang H, et al. Compensatory mechanism for homeostatic blood pressure regulation in Ephx2 gene-disrupted mice. J Biol Chem. 2007;282:2891-8 pubmed
    ..b>Soluble epoxide hydrolase converts epoxyeicosatrienoic acids to their corresponding diols, dihydroxyeicosatrienoic acids, ..
  2. Sinal C, Miyata M, Tohkin M, Nagata K, Bend J, Gonzalez F. Targeted disruption of soluble epoxide hydrolase reveals a role in blood pressure regulation. J Biol Chem. 2000;275:40504-10 pubmed
    ..acid generates a series of regioisomeric epoxyeicosatrienoic acids that can be further metabolized by soluble epoxide hydrolase to the corresponding dihydroxyeicosatrienoic acids...
  3. Seubert J, Sinal C, Graves J, Degraff L, Bradbury J, Lee C, et al. Role of soluble epoxide hydrolase in postischemic recovery of heart contractile function. Circ Res. 2006;99:442-50 pubmed
    ..acid to epoxyeicosatrienoic acids (EETs) which are converted to dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (Ephx2, sEH)...
  4. Frömel T, Jungblut B, Hu J, Trouvain C, Barbosa Sicard E, Popp R, et al. Soluble epoxide hydrolase regulates hematopoietic progenitor cell function via generation of fatty acid diols. Proc Natl Acad Sci U S A. 2012;109:9995-10000 pubmed publisher
    ..plasma levels of these mediators are determined by the activity of cytochrome P450 epoxygenases and the soluble epoxide hydrolase (sEH), and targeting the latter is an effective way of manipulating epoxide levels in vivo...
  5. Barbosa Sicard E, Frömel T, Keserü B, Brandes R, Morisseau C, Hammock B, et al. Inhibition of the soluble epoxide hydrolase by tyrosine nitration. J Biol Chem. 2009;284:28156-63 pubmed publisher
    Inhibition of the soluble epoxide hydrolase (sEH) has beneficial effects on vascular inflammation and hypertension indicating that the enzyme may be a promising target for drug development...
  6. Ai D, Pang W, Li N, Xu M, Jones P, Yang J, et al. Soluble epoxide hydrolase plays an essential role in angiotensin II-induced cardiac hypertrophy. Proc Natl Acad Sci U S A. 2009;106:564-9 pubmed publisher
    ..Epoxyeicosatrienoic acids, hydrolyzed and degraded by soluble epoxide hydrolase (sEH), can function as endothelium-derived hyperpolarizing factors to induce dilation of coronary ..
  7. Liu Y, Dang H, Li D, Pang W, Hammock B, Zhu Y. Inhibition of soluble epoxide hydrolase attenuates high-fat-diet-induced hepatic steatosis by reduced systemic inflammatory status in mice. PLoS ONE. 2012;7:e39165 pubmed publisher
    Non-alcoholic fatty liver disease is associated with obesity and considered an inflammatory disease. Soluble epoxide hydrolase (sEH) is a major enzyme hydrolyzing epoxyeicosatrienoic acids and attenuates their cardiovascular protective ..
  8. Zha W, Edin M, Vendrov K, Schuck R, Lih F, Jat J, et al. Functional characterization of cytochrome P450-derived epoxyeicosatrienoic acids in adipogenesis and obesity. J Lipid Res. 2014;55:2124-36 pubmed publisher
  9. Hutchens M, Nakano T, Dunlap J, Traystman R, Hurn P, Alkayed N. Soluble epoxide hydrolase gene deletion reduces survival after cardiac arrest and cardiopulmonary resuscitation. Resuscitation. 2008;76:89-94 pubmed
    ..by cytochrome P450 arachidonic acid epoxygenases and metabolized through multiple pathways, including soluble epoxide hydrolase (sEH)...
  10. Elmarakby A, Faulkner J, Al Shabrawey M, Wang M, Maddipati K, Imig J. Deletion of soluble epoxide hydrolase gene improves renal endothelial function and reduces renal inflammation and injury in streptozotocin-induced type 1 diabetes. Am J Physiol Regul Integr Comp Physiol. 2011;301:R1307-17 pubmed publisher
    Studies suggest that soluble epoxide hydrolase (sEH) inhibition reduces end-organ damage in cardiovascular diseases...
  11. Yadav V, Hong K, Zeldin D, Nayeem M. Vascular endothelial over-expression of soluble epoxide hydrolase (Tie2-sEH) enhances adenosine A1 receptor-dependent contraction in mouse mesenteric arteries: role of ATP-sensitive K+ channels. Mol Cell Biochem. 2016;422:197-206 pubmed
    b>Soluble epoxide hydrolase (sEH) converts epoxyeicosatrienoic acids that are endothelium-derived hyperpolarizing factors into less active dihydroxyeicosatrienoic acids...
  12. Vardi A, Bosviel R, Rabiau N, Adjakly M, Satih S, Dechelotte P, et al. Soy phytoestrogens modify DNA methylation of GSTP1, RASSF1A, EPH2 and BRCA1 promoter in prostate cancer cells. In Vivo. 2010;24:393-400 pubmed
    ..Epigenetic modifications of DNA, such as the promoter CpG island demethylation of tumor suppressor genes, might be related to the protective effect of soy on prostate cancer. ..
  13. Wepler M, Beloiartsev A, Buswell M, Panigrahy D, Malhotra R, Buys E, et al. Soluble epoxide hydrolase deficiency or inhibition enhances murine hypoxic pulmonary vasoconstriction after lipopolysaccharide challenge. Am J Physiol Lung Cell Mol Physiol. 2016;311:L1213-L1221 pubmed publisher
    ..vasoconstrictors, which are metabolized to less vasoactive dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH)...
  14. Corenblum M, Wise V, Georgi K, Hammock B, Doris P, Fornage M. Altered soluble epoxide hydrolase gene expression and function and vascular disease risk in the stroke-prone spontaneously hypertensive rat. Hypertension. 2008;51:567-73 pubmed
    b>Soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids and represents a novel therapeutic target in cardiovascular disease treatment...
  15. Katragadda D, Batchu S, Cho W, Chaudhary K, Falck J, Seubert J. Epoxyeicosatrienoic acids limit damage to mitochondrial function following stress in cardiac cells. J Mol Cell Cardiol. 2009;46:867-75 pubmed publisher
    ..polyunsaturated fatty acids synthesized from arachidonic acid by CYP2J2 epoxygenase and inactivated by soluble epoxide hydrolase (sEH or Ephx2) to dihydroxyeicosatrienoic acids...
  16. Froogh G, Qin J, Kandhi S, Le Y, Jiang H, Luo M, et al. Female-favorable attenuation of coronary myogenic constriction via reciprocal activations of epoxyeicosatrienoic acids and nitric oxide. Am J Physiol Heart Circ Physiol. 2016;310:H1448-54 pubmed publisher
    ..acids (EETs) are metabolites of arachidonic acid via CYP/epoxygenases, which are catabolized by soluble epoxide hydrolase (sEH) and known to possess cardioprotective properties...
  17. Hennebold J, Mah K, Perez W, Vance J, Stouffer R, Morisseau C, et al. Identification and characterization of an ovary-selective isoform of epoxide hydrolase. Biol Reprod. 2005;72:968-75 pubmed
    ..cDNA revealed that the majority of it, with the exception of the first 44 amino acids, matched soluble epoxide hydrolase (Ephx2, referred to as Ephx2A)...
  18. Zhang G, Panigrahy D, Hwang S, Yang J, Mahakian L, Wettersten H, et al. Dual inhibition of cyclooxygenase-2 and soluble epoxide hydrolase synergistically suppresses primary tumor growth and metastasis. Proc Natl Acad Sci U S A. 2014;111:11127-32 pubmed publisher
    ..from the cyclooxygenase (COX) pathway and epoxyeicosatrienoic acids (EETs) from the cytochrome P450/soluble epoxide hydrolase (sEH) pathway are important eicosanoids that regulate angiogenesis and tumorigenesis...
  19. Qin J, Kandhi S, Froogh G, Jiang H, Luo M, Sun D, et al. Sexually dimorphic phenotype of arteriolar responsiveness to shear stress in soluble epoxide hydrolase-knockout mice. Am J Physiol Heart Circ Physiol. 2015;309:H1860-6 pubmed publisher
    ..the bioavailability of endothelial epoxyeicosatrienoic acids (EETs) via deletion of the gene for soluble epoxide hydrolase (sEH), or downregulation of sEH expression, enhances flow/shear stress-induced dilator responses (FID) ..
  20. Liao J, Hwang S, Li H, Liu J, Hammock B, Yang G. Inhibition of Chronic Pancreatitis and Murine Pancreatic Intraepithelial Neoplasia by a Dual Inhibitor of c-RAF and Soluble Epoxide Hydrolase in LSL-KrasG¹²D/Pdx-1-Cre Mice. Anticancer Res. 2016;36:27-37 pubmed
    ..aberrant metabolites of arachidonic acid play a crucial role in promoting carcinogenesis, in which the soluble epoxide hydrolase (sEH), as a pro-inflammatory enzyme, generally inactivates anti-inflammatory epoxyeicosatrienoic acids (..
  21. Deng Y, Edin M, Theken K, Schuck R, Flake G, Kannon M, et al. Endothelial CYP epoxygenase overexpression and soluble epoxide hydrolase disruption attenuate acute vascular inflammatory responses in mice. FASEB J. 2011;25:703-13 pubmed publisher
    ..However, the effect of increased CYP-mediated EET biosynthesis and decreased soluble epoxide hydrolase (sEH, Ephx2)-mediated EET hydrolysis on vascular inflammation in vivo has not been rigorously ..
  22. Panigrahy D, Kalish B, Huang S, Bielenberg D, Le H, Yang J, et al. Epoxyeicosanoids promote organ and tissue regeneration. Proc Natl Acad Sci U S A. 2013;110:13528-33 pubmed publisher
    ..We also show that soluble epoxide hydrolase inhibitors, which elevate endogenous EET levels, promote liver and lung regeneration...
  23. Hu J, Popp R, Frömel T, Ehling M, Awwad K, Adams R, et al. Müller glia cells regulate Notch signaling and retinal angiogenesis via the generation of 19,20-dihydroxydocosapentaenoic acid. J Exp Med. 2014;211:281-95 pubmed publisher
    ..bioactive lipid epoxides which can be further metabolized to supposedly less active diols by the soluble epoxide hydrolase (sEH)...
  24. Grant D, Spearow J, Storms D, Edelhoff S, Adler D, Disteche C, et al. Chromosomal mapping and expression levels of a mouse soluble epoxide hydrolase gene. Pharmacogenetics. 1994;4:64-72 pubmed
    The chromosomal location of a murine soluble epoxide hydrolase gene was determined using in situ mapping, restriction fragment length polymorphism (RFLP) and simple sequence length polymorphism (SSLP) analysis...
  25. Schuck R, Zha W, Edin M, Gruzdev A, Vendrov K, Miller T, et al. The cytochrome P450 epoxygenase pathway regulates the hepatic inflammatory response in fatty liver disease. PLoS ONE. 2014;9:e110162 pubmed publisher
    ..Furthermore, mice with targeted disruption of Ephx2 (the gene encoding soluble epoxide hydrolase) exhibited restored hepatic and circulating EET levels and a significantly attenuated induction of ..
  26. Yang J, Bratt J, Franzi L, Liu J, Zhang G, Zeki A, et al. Soluble epoxide hydrolase inhibitor attenuates inflammation and airway hyperresponsiveness in mice. Am J Respir Cell Mol Biol. 2015;52:46-55 pubmed publisher
    Control of airway inflammation is critical in asthma treatment. Soluble epoxide hydrolase (sEH) has recently been demonstrated as a novel therapeutic target for treating inflammation, including lung inflammation...
  27. Fife K, Liu Y, Schmelzer K, Tsai H, Kim I, Morisseau C, et al. Inhibition of soluble epoxide hydrolase does not protect against endotoxin-mediated hepatic inflammation. J Pharmacol Exp Ther. 2008;327:707-15 pubmed publisher
    ..The major elimination pathway for EETs is through soluble epoxide hydrolase (sEH)-catalyzed metabolism to dihydroxyeicosatrienoic acids (DHETs)...
  28. Bettaieb A, Koike S, Hsu M, Ito Y, Chahed S, Bachaalany S, et al. Soluble epoxide hydrolase in podocytes is a significant contributor to renal function under hyperglycemia. Biochim Biophys Acta Gen Subj. 2017;1861:2758-2765 pubmed publisher
    ..b>Soluble epoxide hydrolase (sEH, encoded by Ephx2) is a conserved cytosolic enzyme whose inhibition has beneficial effects on renal ..
  29. Kandhi S, Qin J, Froogh G, Jiang H, Luo M, Wolin M, et al. EET-dependent potentiation of pulmonary arterial pressure: sex-different regulation of soluble epoxide hydrolase. Am J Physiol Lung Cell Mol Physiol. 2015;309:L1478-86 pubmed publisher
    ..that suppression of epoxyeicosatrienoic acid (EET) metabolism via genetic knockout of the gene for soluble epoxide hydrolase (sEH-KO), or female-specific downregulation of sEH expression, plays a role in the potentiation of ..
  30. Qin X, Wu Q, Lin L, Sun A, Liu S, Li X, et al. Soluble Epoxide Hydrolase Deficiency or Inhibition Attenuates MPTP-Induced Parkinsonism. Mol Neurobiol. 2015;52:187-95 pubmed publisher
    b>Soluble epoxide hydrolase (sEH) inhibition has been demonstrated to have beneficial effects on various diseases, such as hypertension, diabetes, and brain ischemia...
  31. Li L, Li N, Pang W, Zhang X, Hammock B, Ai D, et al. Opposite effects of gene deficiency and pharmacological inhibition of soluble epoxide hydrolase on cardiac fibrosis. PLoS ONE. 2014;9:e94092 pubmed publisher
    ..EETs are hydrolyzed by soluble epoxide hydrolase (sEH) to form the corresponding diols, thus altering and reducing the activity of these oxylipins...
  32. Keserü B, Barbosa Sicard E, Popp R, Fisslthaler B, Dietrich A, Gudermann T, et al. Epoxyeicosatrienoic acids and the soluble epoxide hydrolase are determinants of pulmonary artery pressure and the acute hypoxic pulmonary vasoconstrictor response. FASEB J. 2008;22:4306-15 pubmed publisher
    ..Given that the intracellular concentration of EETs is determined by the soluble epoxide hydrolase (sEH), we assessed the influence of the sEH and 11,12-EET on pulmonary artery pressure and HPV in the ..
  33. Merkel M, Liu L, Cao Z, Packwood W, Young J, Alkayed N, et al. Inhibition of soluble epoxide hydrolase preserves cardiomyocytes: role of STAT3 signaling. Am J Physiol Heart Circ Physiol. 2010;298:H679-87 pubmed publisher
    b>Soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids (EETs), primarily 14,15-EET. EETs are derived from arachidonic acid via P-450 epoxygenases and are cardioprotective...
  34. Johansson C, Stark A, Sandberg M, Ek B, Rask L, Meijer J. Tissue specific basal expression of soluble murine epoxide hydrolase and effects of clofibrate on the mRNA levels in extrahepatic tissues and liver. Arch Toxicol. 1995;70:61-3 pubmed
    The soluble epoxide hydrolase mRNA level in liver was increased eight-fold upon administration of the hypolipidemic drug and peroxisome proliferator clofibrate for 7 days to mice...
  35. Argiriadi M, Morisseau C, Hammock B, Christianson D. Detoxification of environmental mutagens and carcinogens: structure, mechanism, and evolution of liver epoxide hydrolase. Proc Natl Acad Sci U S A. 1999;96:10637-42 pubmed
    The crystal structure of recombinant murine liver cytosolic epoxide hydrolase (EC 3.3.2.3) has been determined at 2.8-A resolution...
  36. Hanif A, Edin M, Zeldin D, Morisseau C, Falck J, Nayeem M. Vascular Endothelial Over-Expression of Human Soluble Epoxide Hydrolase (Tie2-sEH Tr) Attenuates Coronary Reactive Hyperemia in Mice: Role of Oxylipins and ?-Hydroxylases. PLoS ONE. 2017;12:e0169584 pubmed publisher
    ..effects of EETs are reduced after their hydrolysis to dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). ?-terminal HETEs are formed by ?-hydroxylase family members...
  37. Grant D, Storms D, Hammock B. Molecular cloning and expression of murine liver soluble epoxide hydrolase. J Biol Chem. 1993;268:17628-33 pubmed
    A clofibrate-induced mouse liver cDNA library was prepared and used to isolate the coding sequence for soluble epoxide hydrolase. A 1668-base pair (bp) clone was isolated and found to contain a 1269-bp open reading frame coding for 423 ..
  38. Hanif A, Edin M, Zeldin D, Morisseau C, Nayeem M. Deletion of soluble epoxide hydrolase enhances coronary reactive hyperemia in isolated mouse heart: role of oxylipins and PPARγ. Am J Physiol Regul Integr Comp Physiol. 2016;311:R676-R688 pubmed publisher
    The relationship between soluble epoxide hydrolase (sEH) and coronary reactive hyperemia (CRH) response to a brief ischemic insult is not known...
  39. Wang Q, Huo L, He J, Ding W, Su H, Tian D, et al. Soluble epoxide hydrolase is involved in the development of atherosclerosis and arterial neointima formation by regulating smooth muscle cell migration. Am J Physiol Heart Circ Physiol. 2015;309:H1894-903 pubmed publisher
    Epoxyeicosatrienoic acids (EETs) have beneficial effects on cardiovascular disease. Soluble epoxide hydrolase (sEH) metabolizes EETs to less active diols, thus diminishing their biological activity...
  40. Hercule H, Schunck W, Gross V, Seringer J, Leung F, Weldon S, et al. Interaction between P450 eicosanoids and nitric oxide in the control of arterial tone in mice. Arterioscler Thromb Vasc Biol. 2009;29:54-60 pubmed publisher
    ..We identified a novel interaction between EETs and endothelial NO release using soluble epoxide hydrolase (sEH) -/- and +/+ mice...
  41. Brenneis C, Sisignano M, Coste O, Altenrath K, Fischer M, Angioni C, et al. Soluble epoxide hydrolase limits mechanical hyperalgesia during inflammation. Mol Pain. 2011;7:78 pubmed publisher
    ..Three of the EETs (i.e., 8,9-, 11,12- and 14,15-EET) are rapidly hydrolysed by the enzyme soluble epoxide hydrolase (sEH). Here, we investigated the role of sEH in nociceptive processing during peripheral inflammation...
  42. Liao J, Hwang S, Li H, Yang Y, Yang J, Wecksler A, et al. Inhibition of mutant KrasG12D-initiated murine pancreatic carcinoma growth by a dual c-Raf and soluble epoxide hydrolase inhibitor t-CUPM. Cancer Lett. 2016;371:187-93 pubmed publisher
    ..The soluble epoxide hydrolase (sEH), a pro-inflammatory enzyme, generally inactivates anti-inflammatory and anti-pain ..
  43. Charles R, Rudyk O, Prysyazhna O, Kamynina A, Yang J, Morisseau C, et al. Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase. Proc Natl Acad Sci U S A. 2014;111:8167-72 pubmed publisher
    b>Soluble epoxide hydrolase (sEH) is inhibited by electrophilic lipids by their adduction to Cys521 proximal to its catalytic center...
  44. Sandberg M, Hassett C, Adman E, Meijer J, Omiecinski C. Identification and functional characterization of human soluble epoxide hydrolase genetic polymorphisms. J Biol Chem. 2000;275:28873-81 pubmed
    Human soluble epoxide hydrolase (sEH), an enzyme directing the functional disposition of a variety of endogenous and xenobiotic-derived chemical epoxides, was characterized at the genomic level for interindividual variation capable of ..
  45. Gilroy D, Edin M, De Maeyer R, Bystrom J, Newson J, Lih F, et al. CYP450-derived oxylipins mediate inflammatory resolution. Proc Natl Acad Sci U S A. 2016;113:E3240-9 pubmed publisher
    ..sEH (Ephx2)(-/-) mice, which have elevated epoxy-oxylipins, demonstrated opposing effects to epoxI-treated mice: reduced Ly6c(..
  46. Pradhan I, Ledent C, Mustafa S, Morisseau C, Nayeem M. High salt diet modulates vascular response in A2AAR (+/+) and A 2AAR (-/-) mice: role of sEH, PPARγ, and K ATP channels. Mol Cell Biochem. 2015;404:87-96 pubmed publisher
    ..KATP channels) in A2AAR(+/+) mice, while HS-induced vascular contraction to adenosine is dependent on soluble epoxide hydrolase (sEH) that degrades EETs in A2AAR(-/-) mice...
  47. Zhu Y, Blum M, Hoff U, Wesser T, Fechner M, Westphal C, et al. Renal Ischemia/Reperfusion Injury in Soluble Epoxide Hydrolase-Deficient Mice. PLoS ONE. 2016;11:e0145645 pubmed publisher
    ..EETs are rapidly metabolized to dihydroxyeicosatrienoic acids (DHETs) by the soluble epoxide hydrolase (sEH)...
  48. Nayeem M, Zeldin D, Boegehold M, Morisseau C, Marowsky A, Ponnoth D, et al. Modulation by salt intake of the vascular response mediated through adenosine A(2A) receptor: role of CYP epoxygenase and soluble epoxide hydrolase. Am J Physiol Regul Integr Comp Physiol. 2010;299:R325-33 pubmed publisher
    ..epoxygenase blocker, 10(-5) M including CYP2J2], 12-(3-adamantan-1-yl-ureido)dodecanoic acid [AUDA; soluble epoxide hydrolase (sEH) blocker, 10(-5) M], dibromo-dodecenyl-methylsulfimide [DDMS; CYP omega-hydroxylase (CYP4A blocker),..
  49. Zhong L, Zhou J, Wang D, Zou X, Lou Y, Liu D, et al. Proteomics and bioinformatics analysis of mouse hypothalamic neurogenesis with or without EPHX2 gene deletion. Int J Clin Exp Pathol. 2015;8:12634-45 pubmed
    The aim of this study was to identify differently expressed proteins in the presence and absence of EPHX2 gene in mouse hypothalamus using proteomics profiling and bioinformatics analysis...
  50. Motoki A, Merkel M, Packwood W, Cao Z, Liu L, Iliff J, et al. Soluble epoxide hydrolase inhibition and gene deletion are protective against myocardial ischemia-reperfusion injury in vivo. Am J Physiol Heart Circ Physiol. 2008;295:H2128-34 pubmed publisher
    b>Soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids. EETs are formed from arachidonic acid during myocardial ischemia and play a protective role against ischemic cell death...
  51. Sander A, Sommer K, Neumayer T, Fleming I, Marzi I, Barker J, et al. Soluble epoxide hydrolase disruption as therapeutic target for wound healing. J Surg Res. 2013;182:362-7 pubmed publisher
    ..However, the effect of CYP-derived EETs and soluble epoxide hydrolase (sEH) deletion on wound healing in vivo has not been rigorously investigated...
  52. Strauss K, Gruzdev A, Zeldin D. Altered behavioral phenotypes in soluble epoxide hydrolase knockout mice: effects of traumatic brain injury. Prostaglandins Other Lipid Mediat. 2013;104-105:18-24 pubmed publisher
    ..b>Soluble epoxide hydrolase (Ephx2, sEH) appears to be the predominant pathway for EET metabolism to less active ..
  53. Zhang W, Davis C, Edin M, Lee C, Zeldin D, Alkayed N. Role of endothelial soluble epoxide hydrolase in cerebrovascular function and ischemic injury. PLoS ONE. 2013;8:e61244 pubmed publisher
    b>Soluble Epoxide Hydrolase (sEH) is a key enzyme in the metabolism and termination of action of epoxyeicosatrienoic acids, derivatives of arachidonic acid, which are protective against ischemic stroke...
  54. Harris T, Bettaieb A, Kodani S, Dong H, Myers R, Chiamvimonvat N, et al. Inhibition of soluble epoxide hydrolase attenuates hepatic fibrosis and endoplasmic reticulum stress induced by carbon tetrachloride in mice. Toxicol Appl Pharmacol. 2015;286:102-11 pubmed publisher
    ..Inhibitors of the enzyme soluble epoxide hydrolase (sEH) reduce fibrosis in the heart, pancreas and kidney in several disease models...
  55. Simmons D, Lalley P, Kasper C. Chromosomal assignments of genes coding for components of the mixed-function oxidase system in mice. Genetic localization of the cytochrome P-450PCN and P-450PB gene families and the nadph-cytochrome P-450 oxidoreductase and epoxide hydratase genes. J Biol Chem. 1985;260:515-21 pubmed
    ..Corroboratory data are presented to show that the Eph-1 locus on chromosome 1 is the site of at least one microsomal epoxide hydratase gene.
  56. Gauthier K, Goldman D, Aggarwal N, Chawengsub Y, Falck J, Campbell W. Role of arachidonic acid lipoxygenase metabolites in acetylcholine-induced relaxations of mouse arteries. Am J Physiol Heart Circ Physiol. 2011;300:H725-35 pubmed publisher
    ..Thus, in mouse resistance arteries, 12/15-LO AA metabolites mediate endothelium-dependent relaxations to ACh and AA. ..
  57. Bettaieb A, Chahed S, Tabet G, Yang J, Morisseau C, Griffey S, et al. Effects of soluble epoxide hydrolase deficiency on acute pancreatitis in mice. PLoS ONE. 2014;9:e113019 pubmed publisher
    ..b>Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose inhibition in murine models has beneficial effects in inflammatory ..
  58. Kopkan L, Husková Z, Sporkova A, Varcabová S, Honetschlägerová Z, Hwang S, et al. Soluble epoxide hydrolase inhibition exhibits antihypertensive actions independently of nitric oxide in mice with renovascular hypertension. Kidney Blood Press Res. 2012;35:595-607 pubmed publisher
    The present study was performed to examine whether the blood pressure (BP)-lowering effects of soluble epoxide hydrolase (sEH) inhibition in two-kidney, one-clip (2K1C) Goldblatt hypertension are nitric oxide (NO) dependent...
  59. Roos J, Oancea C, Heinssmann M, Khan D, Held H, Kahnt A, et al. 5-Lipoxygenase is a candidate target for therapeutic management of stem cell-like cells in acute myeloid leukemia. Cancer Res. 2014;74:5244-55 pubmed publisher
    ..Cancer Res; 74(18); 5244-55. ©2014 AACR. ..
  60. Cronin A, Decker M, Arand M. Mammalian soluble epoxide hydrolase is identical to liver hepoxilin hydrolase. J Lipid Res. 2011;52:712-9 pubmed publisher
    ..Here, we report that hepoxilin hydrolysis in liver is mainly catalyzed by soluble epoxide hydrolase (sEH): i) purified mammalian sEH hydrolyses hepoxilin A? and B? with a V(max) of 0.4-2...
  61. Kandhi S, Zhang B, Froogh G, Qin J, Alruwaili N, Le Y, et al. EETs promote hypoxic pulmonary vasoconstriction via constrictor prostanoids. Am J Physiol Lung Cell Mol Physiol. 2017;313:L350-L359 pubmed publisher
    ..acids (EETs) facilitate pulmonary responses to hypoxia, male wild-type (WT) and soluble-epoxide hydrolase knockout (sEH-KO) mice, and WT mice chronically fed a sEH inhibitor (t-TUCB; 1 mg·kg-1·day-1) were ..
  62. Argiriadi M, Morisseau C, Goodrow M, Dowdy D, Hammock B, Christianson D. Binding of alkylurea inhibitors to epoxide hydrolase implicates active site tyrosines in substrate activation. J Biol Chem. 2000;275:15265-70 pubmed
    The structures of two alkylurea inhibitors complexed with murine soluble epoxide hydrolase have been determined by x-ray crystallographic methods...
  63. Roche C, Besnier M, Cassel R, Harouki N, Coquerel D, Guerrot D, et al. Soluble epoxide hydrolase inhibition improves coronary endothelial function and prevents the development of cardiac alterations in obese insulin-resistant mice. Am J Physiol Heart Circ Physiol. 2015;308:H1020-9 pubmed publisher
    This study addressed the hypothesis that inhibiting the soluble epoxide hydrolase (sEH)-mediated degradation of epoxy-fatty acids, notably epoxyeicosatrienoic acids, has an additional impact against cardiovascular damage in insulin ..
  64. Marcus R, Gale N, Morrison M, Mason C, Yancopoulos G. Eph family receptors and their ligands distribute in opposing gradients in the developing mouse retina. Dev Biol. 1996;180:786-9 pubmed
    ..The distinct distributions of Eph family members suggest that each subclass specifies positional information along independent retinal axes. ..
  65. Ren Q, Ma M, Ishima T, Morisseau C, Yang J, Wagner K, et al. Gene deficiency and pharmacological inhibition of soluble epoxide hydrolase confers resilience to repeated social defeat stress. Proc Natl Acad Sci U S A. 2016;113:E1944-52 pubmed publisher
    ..The soluble epoxide hydrolase (sEH) plays a key role in the inflammation that is involved in depression...
  66. Chen G, Xu R, Wang Y, Wang P, Zhao G, Xu X, et al. Genetic disruption of soluble epoxide hydrolase is protective against streptozotocin-induced diabetic nephropathy. Am J Physiol Endocrinol Metab. 2012;303:E563-75 pubmed publisher
    ..Genetic disruption of soluble epoxide hydrolase (sEH/EPHX2) results in increased EET levels through decreased hydrolysis...
  67. Bianco R, Agassandian K, Cassell M, Spector A, Sigmund C. Characterization of transgenic mice with neuron-specific expression of soluble epoxide hydrolase. Brain Res. 2009;1291:60-72 pubmed publisher
    b>Soluble epoxide hydrolase (sEH) is the major enzyme responsible for the metabolism and inactivation of epoxyeicosatrienoic acids (EETs)...
  68. Fairbanks S, Young J, Nelson J, Davis C, Koerner I, Alkayed N. Mechanism of the sex difference in neuronal ischemic cell death. Neuroscience. 2012;219:183-91 pubmed publisher
    ..to in-vitro ischemia than cells from females, and if this is related to increased expression of soluble epoxide hydrolase (sEH)...
  69. Simpkins A, Rudic R, Roy S, Tsai H, Hammock B, Imig J. Soluble epoxide hydrolase inhibition modulates vascular remodeling. Am J Physiol Heart Circ Physiol. 2010;298:H795-806 pubmed publisher
    The soluble epoxide hydrolase enzyme (SEH) and vascular remodeling are associated with cardiovascular disease...
  70. Li Y, Yu G, Yuan S, Tan C, Lian P, Fu L, et al. Cigarette Smoke-Induced Pulmonary Inflammation and Autophagy Are Attenuated in Ephx2-Deficient Mice. Inflammation. 2017;40:497-510 pubmed publisher
    ..For this reason, the effect of decreased soluble epoxide hydrolase (sEH, Ephx2)-mediated EET hydrolysis on inflammation, emphysema, lung function, and autophagy was here ..
  71. Charles R, Burgoyne J, Mayr M, Weldon S, Hubner N, Dong H, et al. Redox regulation of soluble epoxide hydrolase by 15-deoxy-delta-prostaglandin J2 controls coronary hypoxic vasodilation. Circ Res. 2011;108:324-34 pubmed publisher
    ..with biotinylated 15d-PGJ(2) identified novel vascular targets to which it adducts, most notably soluble epoxide hydrolase (sEH)...
  72. Sun D, Cuevas A, Gotlinger K, Hwang S, Hammock B, Schwartzman M, et al. Soluble epoxide hydrolase-dependent regulation of myogenic response and blood pressure. Am J Physiol Heart Circ Physiol. 2014;306:H1146-53 pubmed publisher
    ..EETs possess cardioprotective properties and are catalyzed by soluble epoxide hydrolase (sEH) to dihydroxyeicosatrienoic acids (DHETs) that lack vasoactive property...
  73. Shen L, Peng H, Peng R, Fan Q, Zhao S, Xu D, et al. Inhibition of soluble epoxide hydrolase in mice promotes reverse cholesterol transport and regression of atherosclerosis. Atherosclerosis. 2015;239:557-65 pubmed publisher
    ..HDLs have a protective role in atherosclerosis by mediating reverse cholesterol transport (RCT). Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose inhibition has various beneficial effects on cardiovascular disease...