Identification of two epoxide hydrolases in Caenorhabditis elegans that metabolize mammalian lipid signaling molecules.
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.
Harris
Todd R
TR
Department of Entomology and Cancer Research Center, University of California, One Shields Avenue, Davis, CA 95616, USA.
Aronov
Pavel A
PA
Jones
Paul D
PD
Tanaka
Hiromasa
H
Arand
Michael
M
Hammock
Bruce D
BD
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
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