Decoding functional metabolomics with docosahexaenoyl ethanolamide (DHEA) identifies novel bioactive signals
- Author(s): Yang, R
- Fredman, G
- Krishnamoorthy, S
- Agrawal, N
- Irimia, D
- Piomelli, D
- Serhan, CN
- et al.
Published Web Locationhttps://doi.org/10.1074/jbc.M111.237990
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-MSMS- 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 EC503.9 × 10-10and 1.0 × 10-10M. 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. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
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