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Decoding Functional Metabolomics With Docosahexaenoyl Ethanolamide (DHEA) Identifies Novel Bioactive Signals

Rong Yang, Gabrielle Fredman, Sriram Krishnamoorthy, Nitin Agrawal, Daniel Irimia, Daniele Piomelli, Charles N Serhan

J Biol Chem. 2011 Sep 9;286(36):31532-41.

PMID: 21757729

Abstract:

Neuroinflammation and traumatic brain injury involve activation of inflammatory cells and production of local pro-inflammatory mediators that can amplify tissue damage. Using LC-UV-MS-MS-based lipidomics in tandem with functional screening at the single-cell level in microfluidic chambers, we identified a series of novel bioactive oxygenated docosahexaenoyl ethanolamide- (DHEA) derived products that regulated leukocyte motility. These included 10,17-dihydroxydocosahexaenoyl ethanolamide (10,17-diHDHEA) and 15-hydroxy-16(17)-epoxy-docosapentaenoyl ethanolamide (15-HEDPEA), each of which was an agonist of recombinant CB2 receptors with EC(50) 3.9 × 10(-10) and 1.0 × 10(-10) M. In human whole blood, 10,17-diHDHEA and 15-HEDPEA at concentrations as low as 10 pM each prevented formation of platelet-leukocyte aggregates involving either platelet-monocyte or platelet-polymorphonuclear leukocyte. In vivo, 15-HEDPEA was organ-protective in mouse reperfusion second organ injury. Together these results indicate that DHEA oxidative metabolism produces potent novel molecules with anti-inflammatory and organ-protective properties.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP162758943 Docosahexaenoyl ethanolamide Docosahexaenoyl ethanolamide 162758-94-3 Price
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