Evidence map›Paper›PMID 28384353›Full record

ArticlePloS one2017

Generation and characterization of epoxide hydrolase 3 (EPHX3)-deficient mice.

Samantha L Hoopes, Artiom Gruzdev, Matthew L Edin, Joan P Graves, J Alyce Bradbury, Gordon P Flake, Fred B Lih, Laura M DeGraff, Darryl C Zeldin

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.1field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. The Multifaceted Role of Epoxide Hydrolases in Human Health and Disease.International journal of molecular sciences · 2020
    Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Samantha L HoopesDivision of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, United States of America.
Artiom GruzdevDivision of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, United States of America.
Matthew L EdinDivision of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, United States of America.ORCID http://orcid.org/0000-0002-7042-500X
Joan P GravesDivision of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, United States of America.
J Alyce BradburyDivision of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, United States of America.
Gordon P FlakeDivision of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, United States of America.
Fred B LihDivision of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, United States of America.
Laura M DeGraffDivision of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, United States of America.
Darryl C ZeldinDivision of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, United States of America.
National Institute of Environmental Health Sciences · US

Funding

Molecular Genetics Support to Identify Gene/Environment Interactions in DiseaseZICES102546 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI GERRISH, KEVIN · 2009 to 2025
$30.5M
Characterization And Functional Significance Of P450 Arachidonate EpoxygenasesZIAES025034 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI ZELDIN, DARRYL C · 2009 to 2025
$18.6M
Mass Spectrometry QuantitationZICES103005 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WILLIAMS, JASON · 2018 to 2025
$9.2M
Quantitative ProteomicsZIAES103005 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI DETERDING, LEESA · 2011 to 2017
$5.6M
P450 Arachidonate EpoxygenasesZ01ES025034 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI ZELDIN, DARRYL C · 1995 to 2008
$2.2M
Intramural NIH HHS Z01 ES025034
6 · The paper itself

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.

Indexed as

AnimalsBody WeightEpoxide HydrolasesFemaleInflammationLipopolysaccharidesMaleMiceMice, KnockoutOrgan SizeReverse Transcriptase Polymerase Chain ReactionEpoxide HydrolasesLipopolysaccharides

Identifiers

PMID28384353
PMCPMC5383309
OpenAlexW2604153693

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.