Caenorhabditis elegans harbours several CYP (cytochrome P450) genes that are homologous with mammalian CYP isoforms important to the production of physiologically active AA (arachidonic acid) metabolites. We tested the hypothesis that mammals and C. elegans may share similar basic mechanisms of CYP-dependent eicosanoid formation and action. We focused on CYP33E2, an isoform related to the human AA-epoxygenases CYP2C8 and CYP2J2. Co-expression of CYP33E2 with the human NADPH–CYP reductase in insect cells resulted in the reconstitution of an active microsomal mono-oxygenase system that metabolized EPA (eicosapentaenoic acid) and, with lower activity, also AA to specific sets of regioisomeric epoxy- and hydroxy-derivatives. The main products included 17,18-epoxyeicosatetraenoic acid from EPA and 19-hydroxyeicosatetraenoic acid from AA. Using nematode worms carrying a pCYP33E2::GFP reporter construct, we found that CYP33E2 is exclusively expressed in the pharynx, where it is predominantly localized in the marginal cells. RNAi (RNA interference)-mediated CYP33E2 expression silencing as well as treatments with inhibitors of mammalian AA-metabolizing CYP enzymes, significantly reduced the pharyngeal pumping frequency of adult C. elegans. These results demonstrate that EPA and AA are efficient CYP33E2 substrates and suggest that CYP–eicosanoids, influencing in mammals the contractility of cardiomyocytes and vascular smooth muscle cells, may function in C. elegans as regulators of the pharyngeal pumping activity.
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Research Article|
April 13 2011
Eicosanoid formation by a cytochrome P450 isoform expressed in the pharynx of Caenorhabditis elegans
Mandy Kosel;
Mandy Kosel
1
*Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany
†Humboldt-Universität zu Berlin, Department of Biology, Freshwater and Stress Ecology, Spaethstrasse 80/81, 12437 Berlin, Germany
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Waltraud Wild;
Waltraud Wild
1
†Humboldt-Universität zu Berlin, Department of Biology, Freshwater and Stress Ecology, Spaethstrasse 80/81, 12437 Berlin, Germany
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Alexandra Bell;
Alexandra Bell
†Humboldt-Universität zu Berlin, Department of Biology, Freshwater and Stress Ecology, Spaethstrasse 80/81, 12437 Berlin, Germany
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Michael Rothe;
Michael Rothe
‡Lipidomix GmbH, Robert-Rössle-Strasse 10, B55, 13125 Berlin, Germany
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Carsten Lindschau;
Carsten Lindschau
§Hannover Medical School and Medical Faculty of the Charité, Experimental and Clinical Research Center, Robert-Rössle-Strasse 10, 13125 Berlin, Germany
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Christian E. W. Steinberg;
Christian E. W. Steinberg
†Humboldt-Universität zu Berlin, Department of Biology, Freshwater and Stress Ecology, Spaethstrasse 80/81, 12437 Berlin, Germany
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Wolf-Hagen Schunck;
Wolf-Hagen Schunck
*Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany
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Ralph Menzel
Ralph Menzel
2
†Humboldt-Universität zu Berlin, Department of Biology, Freshwater and Stress Ecology, Spaethstrasse 80/81, 12437 Berlin, Germany
2To whom correspondence should be addressed (email ralph.menzel@biologie.hu-berlin.de).
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Publisher: Portland Press Ltd
Received:
November 23 2010
Revision Received:
February 10 2011
Accepted:
February 11 2011
Accepted Manuscript online:
February 11 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 435 (3): 689–700.
Article history
Received:
November 23 2010
Revision Received:
February 10 2011
Accepted:
February 11 2011
Accepted Manuscript online:
February 11 2011
Citation
Mandy Kosel, Waltraud Wild, Alexandra Bell, Michael Rothe, Carsten Lindschau, Christian E. W. Steinberg, Wolf-Hagen Schunck, Ralph Menzel; Eicosanoid formation by a cytochrome P450 isoform expressed in the pharynx of Caenorhabditis elegans. Biochem J 1 May 2011; 435 (3): 689–700. doi: https://doi.org/10.1042/BJ20101942
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