Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 278, Issue 17, Pages 14677-14687Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M300218200
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Funding
- NIDCR NIH HHS [P01-DE13499] Funding Source: Medline
- NIDDK NIH HHS [K01 DK060583-03, DK60583] Funding Source: Medline
- NIGMS NIH HHS [GM38765] Funding Source: Medline
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Docosahexaenoic acid (DHA, C22:6) is highly enriched in brain, synapses, and retina and is a major w-3 fatty acid. Deficiencies in this essential fatty acid are reportedly associated with neuronal function, cancer, and inflammation. Here, using new lipidomic analyses employing high performance liquid chromatography coupled with a photodiode-array detector and a tandem mass spectrometer, a novel series of endogenous mediators was identified in blood, leukocytes, brain, and glial cells as 17S-hydroxy-containing docosanoids denoted as docosatrienes (the main bioactive member of the series was 10,17S-docosatriene) and 17S series resolvins. These novel mediators were biosynthesized via epoxide-containing intermediates and proved potent (pico- to nanomolar range) regulators of both leukocytes reducing infiltration in vivo and glial cells blocking their cytokine production. These results indicate that DHA is the precursor to potent protective mediators generated via enzymatic oxygenations to novel docosatrienes and 17S series resolvins that each regulate events of interest in inflammation and resolution.
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