Resolvin D1, protectin D1, and related docosahexaenoic acid-derived products: Analysis via electrospray/low energy tandem mass spectrometry based on spectra and fragmentation mechanisms.
Resolvin D1 (RvD1) and protectin D1 (Neuroprotectin D1, PD1/NPD1) are newly identified anti-inflammatory lipid mediators biosynthesized from docosahexaenoic acid (DHA). In this report, the spectra-structure correlations and fragmentation mechanisms were studied using electrospray low-energy collision-induced dissociation tandem mass spectrometry (MS/MS) for biogenic RvD1 and PD1, as well as mono-hydroxy-DHA and related hydroperoxy-DHA. The loss of H2O and CO2 in the spectra indicates the number of functional group(s). Chain-cut ions are the signature of the positions and numbers of functional groups and double bonds. The observed chain-cut ion is equivalent to a hypothetical homolytic-segment (cc, cm, mc, or mm) with addition or extraction of up to 2 protons (H). The alpha-cleavage ions are equivalent to: [cc + H], with H from the hydroxyl through a beta-ene or gamma-ene rearrangement; [cm - 2H], with 2H from hydroxyls of PD1 through a gamma-ene rearrangement, or 1H from the hydroxyl and the other H from the alpha-carbon of mono-HDHA through an alpha-H-beta-ene rearrangement; [mc - H], with H from hydroxyl through a beta-ene or gamma-ene rearrangement, or from the alpha-carbon through an alpha-H-beta-ene rearrangement; or [mm] through charge-direct fragmentations. The beta-ene or gamma-ene facilitates the H shift to gamma position and alpha-cleavage. Deuterium labeling confirmed the assignment of MS/MS ions and the fragmentation mechanisms. Based on the MS/MS spectra and fragmentation mechanisms, we identified RvD1, PD1, and mono-hydroxy-DHA products in human neutrophils and blood, trout head-kidney, and stroke-injury murine brain-tissue.
Hong
Song
S
Analytical Core, Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Lu
Yan
Y
Yang
Rong
R
Gotlinger
Katherine H
KH
Petasis
Nicos A
NA
Serhan
Charles N
CN
D002851:Chromatography, High Pressure Liquid; D004281:Docosahexaenoic Acids / Q000032:analysis / Q000737:chemistry*; D018836:Inflammation Mediators / Q000032:analysis* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation / Q000379:methods*
D018836:Inflammation Mediators; C487679:protectin D1; C518399:resolvin D1; D004281:Docosahexaenoic Acids