ArticlePloS one2017
Generation and characterization of epoxide hydrolase 3 (EPHX3)-deficient mice.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- The comparative physiological, biochemical and whole transcriptome analysis of Ross 308 broilers under different wind conditions.Poultry science · 2025Article
- Epoxide Hydrolase Inhibitors for the Treatment of Alzheimer's Disease and Other Neurological Disorders: A Comprehensive Review.Biomedicines · 2025Review
- Role of the soluble epoxide hydrolase in keratinocyte proliferation and sensitivity of skin to inflammatory stimuli.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Role of the soluble epoxide hydrolase in the hair follicle stem cell homeostasis and hair growth.Pflugers Archiv : European journal of physiology · 2022Article
- TPPU treatment of burned mice dampens inflammation and generation of bioactive DHET which impairs neutrophil function.Scientific reports · 2021Article
- α/β-Hydrolase Domain (ABHD) Inhibitors as New Potential Therapeutic Options against Lipid-Related Diseases.Journal of medicinal chemistry · 2021Review
- Relative Importance of Soluble and Microsomal Epoxide Hydrolases for the Hydrolysis of Epoxy-Fatty Acids in Human Tissues.International journal of molecular sciences · 2021Article
- The Multifaceted Role of Epoxide Hydrolases in Human Health and Disease.International journal of molecular sciences · 2020Review
- Review
- Mechanism of Chronic Kidney Disease Progression and Novel Biomarkers: A Metabolomic Analysis of Experimental Glomerulonephritis.Metabolites · 2020Article
- New Lipid Mediators in Retinal Angiogenesis and Retinopathy.Frontiers in pharmacology · 2019Review
- Catalytic activities of mammalian epoxide hydrolases withJournal of lipid research · 2018Article
- Epoxide hydrolase 1 (EPHX1) hydrolyzes epoxyeicosanoids and impairs cardiac recovery after ischemia.The Journal of biological chemistry · 2018Article
- Epoxide hydrolase 3 (Ephx3) gene disruption reduces ceramide linoleate epoxide hydrolysis and impairs skin barrier function.The Journal of biological chemistryArticle
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play an important role in blood pressure regulation, protection against ischemia-reperfusion injury, angiogenesis, and inflammation. Epoxide hydrolases metabolize EETs to their corresponding diols (dihydroxyeicosatrienoic acids; DHETs) which are biologically less active. Microsomal epoxide hydrolase (EPHX1, mEH) and soluble epoxide hydrolase (EPHX2, sEH) were identified >30 years ago and are capable of hydrolyzing EETs to DHETs. A novel epoxide hydrolase, EPHX3, was recently identified by sequence homology and also exhibits epoxide hydrolase activity in vitro with a substrate preference for 9,10-epoxyoctadecamonoenoic acid (EpOME) and 11,12-EET. EPHX3 is highly expressed in the skin, lung, stomach, esophagus, and tongue; however, its endogenous function is unknown. Therefore, we investigated the impact of genetic disruption of Ephx3 on fatty acid epoxide hydrolysis and EET-related physiology in mice. Ephx3-/- mice were generated by excising the promoter and first four exons of the Ephx3 gene using Cre-LoxP methodology. LC-MS/MS analysis of Ephx3-/- heart, lung, and skin lysates revealed no differences in endogenous epoxide:diol ratios compared to wild type (WT). Ephx3-/- mice also exhibited no change in plasma levels of fatty acid epoxides and diols relative to WT. Incubations of cytosolic and microsomal fractions prepared from Ephx3-/- and WT stomach, lung, and skin with synthetic 8,9-EET, 11,12-EET, and 9,10-EpOME revealed no significant differences in rates of fatty acid diol formation between the genotypes. Ephx3-/- hearts had similar functional recovery compared to WT hearts following ischemia/reperfusion injury. Following intranasal lipopolysaccharide (LPS) exposure, Ephx3-/- mice were not different from WT in terms of lung histology, bronchoalveolar lavage fluid cell counts, or fatty acid epoxide and diol levels. We conclude that genetic disruption of Ephx3 does not result in an overt phenotype and has no significant effects on the metabolism of EETs or EpOMEs in vivo.
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