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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-54382

Cronin, A; Decker, M; Arand, M (2011). Mammalian soluble epoxide hydrolase is identical to liver hepoxilin hydrolase. Journal of Lipid Research, 52(4):712-719.

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Abstract

Hepoxilins are lipid signaling molecules derived from arachidonic acid through the 12-lipoxygenase pathway. These trans-epoxy hydroxy eicosanoids play a role in a variety of physiological processes, including inflammation, neurotransmission, and formation of skin barrier function. Mammalian hepoxilin hydrolase, partly purified from rat liver, has earlier been reported to degrade hepoxilins to trioxilins. Here, we report that hepoxilin hydrolysis in liver is mainly catalyzed by soluble epoxide hydrolase (sEH): i) purified mammalian sEH hydrolyses hepoxilin A₃ and B₃ with a V(max) of 0.4-2.5 μmol/mg/min; ii) the highly selective sEH inhibitors N-adamantyl-N'-cyclohexyl urea and 12-(3-adamantan-1-yl-ureido) dodecanoic acid greatly reduced hepoxilin hydrolysis in mouse liver preparations; iii) hepoxilin hydrolase activity was abolished in liver preparations from sEH(-/-) mice; and iv) liver homogenates of sEH(-/-) mice show elevated basal levels of hepoxilins but lowered levels of trioxilins compared with wild-type animals. We conclude that sEH is identical to previously reported hepoxilin hydrolase. This is of particular physiological relevance because sEH is emerging as a novel drug target due to its major role in the hydrolysis of important lipid signaling molecules such as epoxyeicosatrienoic acids. sEH inhibitors might have undesired side effects on hepoxilin signaling.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:25 Jan 2012 21:44
Last Modified:17 Jul 2014 21:04
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0022-2275
Additional Information:This research was originally published in: Cronin, A; Decker, M; Arand, M (2011). Mammalian soluble epoxide hydrolase is identical to liver hepoxilin hydrolase. Journal of Lipid Research, 52(4):712-71 © the American Society for Biochemistry and Molecular Biology.
Publisher DOI:10.1194/jlr.M009639
PubMed ID:21217101
Citations:Web of Science®. Times Cited: 8
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Scopus®. Citation Count: 8

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