Journal
JOURNAL OF LIPID RESEARCH
Volume 51, Issue 12, Pages 3481-3490Publisher
ELSEVIER
DOI: 10.1194/jlr.M006007
Keywords
soluble epoxide hydrolase; central nervous system; pain
Categories
Funding
- National Institute of Environmental Health Sciences [ES02710, ES013933]
- NIEHS [P42 ES04699]
- NIGMS [GM078167]
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Beneficial physiological effects of long-chain n-3 polyunsaturated fatty acids are widely accepted but the mechanism(s) by which these fatty acids act remains unclear. Herein, we report the presence, distribution, and regulation of the levels of n-3 epoxy-fatty acids by soluble epoxide hydrolase (sEH) and a direct antinociceptive role of n-3 epoxy-fatty acids, specifically those originating from docosahexaenoic acid (DHA). The monoepoxides of the C18:1 to C22:6 fatty acids in both the n-6 and n-3 series were prepared and the individual regioisomers purified. The kinetic constants of the hydrolysis of the pure regioisomers by sEH were measured. Surprisingly, the best substrates are the mid-chain DHA epoxides. We also demonstrate that the DHA epoxides are present in considerable amounts in the rat central nervous system. Furthermore, using an animal model of pain associated with inflammation, we show that DHA epoxides, but neither the parent fatty acid nor the corresponding diols, selectively modulate nociceptive pathophysiology.jlr Our findings support an important function of epoxy-fatty acids in the n-3 series in modulating nociceptive signaling. Consequently, the DHA and eicosapentaenoic acid epoxides may be responsible for some of the beneficial effects associated with dietary n-3 fatty acid intake.-Morisseau, C., B. Inceoglu, K. Schmelzer, H-J. Tsai, S. L. Jinks, C. M. Hegedus, and B. D. Hammock. Naturally occurring monoepoxides of eicosapentaenoic acid and docosahexaenoic acid are bioactive antihyperalgesic lipids. J. Lipid Res. 2010. 51: 3481-3490.
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