Full characterization of PDX, a neuroprotectin/protectin D1 isomer, which inhibits blood platelet aggregation.
Our study aimed to establish the complete structure of the main dihydroxy conjugated triene issued from the lipoxygenation (soybean enzyme) of docosahexaenoic acid, named PDX, an isomer of protectin/neuroprotectin D1 (PD1/NPD1) described by Bazan and Serhan. NMR approaches and other chemical characterization (e.g. GC-MS, HPLC and LC-MS/MS) indicated that PDX is 10(S),17(S)-dihydroxy-docosahexa-4Z,7Z,11E,13Z,15E,19Z-enoic acid. The use of (18)O(2) and mass spectrometry showed that PDX is a double lipoxygenation product. Its structure differs from PD1, with E,Z,E geometry (PDX) instead of E,E,Z (PD1) and S configuration at carbon 10 instead of R. PDX inhibits human blood platelet aggregation at sub-micromolar concentrations.
Chen
P
P
Université de Lyon, Inserm UMR 870, Insa-Lyon, RMND/IMBL, Inra 1235, 69621 Villeurbanne, France.
Fenet
B
B
Michaud
S
S
Tomczyk
N
N
Véricel
E
E
Lagarde
M
M
Guichardant
M
M
D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D002244:Carbon / Q000737:chemistry; D004281:Docosahexaenoic Acids / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006878:Hydroxides / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010974:Platelet Aggregation / Q000187:drug effects*; D013025:Glycine max / Q000201:enzymology; D013237:Stereoisomerism
D006878:Hydroxides; C487679:protectin D1; D004281:Docosahexaenoic Acids; D002244:Carbon; C031356:hydroxide ion; D001093:Arachidonate 15-Lipoxygenase