title: Identification of two epoxide hydrolases in Caenorhabditis elegans that metabolize mammalian lipid signaling molecules.
abstract: We have identified two genes in the genomic database for Caenorhabditis elegans that code for proteins with significant sequence similarity to the mammalian soluble epoxide hydrolase (sEH). The respective transcripts were cloned from a mixed stage cDNA library from C. elegans. The corresponding proteins obtained after recombinant expression in insect cells hydrolyzed standard epoxide hydrolase substrates, including epoxyeicosatrienoic acids (EETs) and leukotoxins (EpOMEs). The enzyme activity was inhibited by urea-based compounds originally designed to inhibit the mammalian sEH. In vivo inhibition of the enzymes using the most potent of these compounds resulted in elevated levels of the EpOMEs in the nematode. These results suggest that the hydrolases are involved in the metabolism of possible lipid signaling molecules in C. elegans.
authors.affiliation: Department of Entomology and Cancer Research Center, University of California, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Todd R
authors.initials: TR
authors.lastname: Harris
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Aronov
authors.forename: Paul D
authors.initials: PD
authors.lastname: Jones
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Tanaka
authors.forename: Michael
authors.initials: M
authors.lastname: Arand
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D005098:Exotoxins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D015723:Gene Library; D008041:Linoleic Acids / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009829:Oleic Acids / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D013379:Substrate Specificity
chemical_list: C119104:12,13-epoxy-9-octadecenoic acid; D029742:Caenorhabditis elegans Proteins; D005098:Exotoxins; D005456:Fluorescent Dyes; D008041:Linoleic Acids; D009829:Oleic Acids; D011994:Recombinant Proteins; C018579:leukotoxin; C051208:9,10-epoxy-12-octadecenoic acid; D004851:Epoxide Hydrolases