Role of CYP eicosanoids in the regulation of pharyngeal pumping and food uptake in Caenorhabditis elegans[S]

Journal of Lipid Research

John R. Falck¹  Yiwen Zhou²  Michael Rothe³  Wolf-Hagen Schunck⁴  Ralph Menzel⁵ 

[1] Department of Biochemistry, University of Texas Southwestern, Dallas, TX 75390;Department of Biology, Ecology, Humboldt University of Berlin, 10115 Berlin, Germany;Lipidomix GmbH, 13125 Berlin, Germany;Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany;To whom correspondence should be addressed;

关键词: cytochrome P450;    fatty acid;    omega-3 fatty acids;    lipidomics;    pharynx;    17,18-epoxyeicosatetraenoic acid;   

DOI  :  

来源: DOAJ

【 摘 要 】

Cytochrome P450 (CYP)-dependent eicosanoids comprise epoxy- and hydroxy-metabolites of long-chain PUFAs (LC-PUFAs). In mammals, CYP eicosanoids contribute to the regulation of cardiovascular and renal function. Caenorhabditis elegans produces a large set of CYP eicosanoids; however, their role in worm's physiology is widely unknown. Mutant strains deficient in LC-PUFA/eicosanoid biosynthesis displayed reduced pharyngeal pumping frequencies. This impairment was rescued by long-term eicosapentaenoic and/or arachidonic acid supplementation, but not with a nonmetabolizable LC-PUFA analog. Short-term treatment with 17,18-epoxyeicosatetraenoic acid (17,18-EEQ), the most abundant CYP eicosanoid in C. elegans, was as effective as long-term LC-PUFA supplementation in the mutant strains. In contrast, 20-HETE caused decreased pumping frequencies. The opposite effects of 17,18-EEQ and 20-HETE were mirrored by the actions of neurohormones. 17,18-EEQ mimicked the stimulating effect of serotonin when added to starved worms, whereas 20-HETE shared the inhibitory effect of octopamine in the presence of abundant food. In wild-type worms, serotonin increased free 17,18-EEQ levels, whereas octopamine selectively induced the synthesis of hydroxy-metabolites. These results suggest that CYP eicosanoids may serve as second messengers in the regulation of pharyngeal pumping and food uptake in C. elegans.

【 授权许可】

Unknown