| http://purl.uniprot.org/citations/29298899 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29298899 | http://www.w3.org/2000/01/rdf-schema#comment | "Stimuli such as inflammation or hypoxia induce cytochrome P450 epoxygenase-mediated production of arachidonic acid-derived epoxyeicosatrienoic acids (EETs). EETs have cardioprotective, vasodilatory, angiogenic, anti-inflammatory, and analgesic effects, which are diminished by EET hydrolysis yielding biologically less active dihydroxyeicosatrienoic acids (DHETs). Previous in vitro assays have suggested that epoxide hydrolase 2 (EPHX2) is responsible for nearly all EET hydrolysis. EPHX1, which exhibits slow EET hydrolysis in vitro, is thought to contribute only marginally to EET hydrolysis. Using Ephx1-/-, Ephx2-/-, and Ephx1-/-Ephx2-/- mice, we show here that EPHX1 significantly contributes to EET hydrolysis in vivo Disruption of Ephx1 and/or Ephx2 genes did not induce compensatory changes in expression of other Ephx genes or CYP2 family epoxygenases. Plasma levels of 8,9-, 11,12-, and 14,15-DHET were reduced by 38, 44, and 67% in Ephx2-/- mice compared with wildtype (WT) mice, respectively; however, plasma from Ephx1-/-Ephx2-/- mice exhibited significantly greater reduction (100, 99, and 96%) of those respective DHETs. Kinetic assays and FRET experiments indicated that EPHX1 is a slow EET scavenger, but hydrolyzes EETs in a coupled reaction with cytochrome P450 to limit basal EET levels. Moreover, we also found that EPHX1 activities are biologically relevant, as Ephx1-/-Ephx2-/- hearts had significantly better postischemic functional recovery (71%) than both WT (31%) and Ephx2-/- (51%) hearts. These findings indicate that Ephx1-/-Ephx2-/- mice are a valuable model for assessing EET-mediated effects, uncover a new paradigm for EET metabolism, and suggest that dual EPHX1 and EPHX2 inhibition may represent a therapeutic approach to manage human pathologies such as myocardial infarction."xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.ra117.000298"xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/author | "Singh R."xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/author | "Edin M.L."xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/author | "Lih F.B."xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/author | "Zeldin D.C."xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/author | "Arand M."xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/author | "Bradbury J.A."xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/author | "Graves J.P."xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/author | "DeGraff L.M."xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/author | "Gruzdev A."xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/author | "Hoopes S.L."xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/author | "Orjuela Leon A.C."xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/author | "Arbes S.J."xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/author | "Hamedani B.G."xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/pages | "3281-3292"xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/title | "Epoxide hydrolase 1 (EPHX1) hydrolyzes epoxyeicosanoids and impairs cardiac recovery after ischemia."xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://purl.uniprot.org/core/volume | "293"xsd:string |
| http://purl.uniprot.org/citations/29298899 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/29298899 |
| http://purl.uniprot.org/citations/29298899 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/29298899 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z3T1-mappedCitation-29298899 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29298899 |
| http://purl.uniprot.org/uniprot/#_A8JYK8-mappedCitation-29298899 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29298899 |