Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation.
Docosahexaenoic acid (DHA), an important component of marine lipids, exhibits anti-inflammatory activity related to some of its oxygenated metabolites, such as neuroprotectin/protectin D1 [NPD1/PD1; 10(R),17(S)-dihydroxy-docosa-4Z,7Z, 11E,13E,15Z,19Z-hexaenoic acid] produced through the 15-lipoxygenase pathway. However, other metabolites from DHA can be produced through this pathway, and other polyunsaturated fatty acids (PUFAs) of nutritional value may be oxygenated as well. Their biological activities remain unknown. Isomers of protectin D1 were synthesized using soybean lipoxygenase and tested for their ability to inhibit human blood platelet aggregation. A geometric isomer called PDX, previously described with the 11E,13Z,15E geometry, instead of 11E,13E,15Z in PD1, inhibited platelet aggregation at submicromolar concentrations when induced by either collagen, arachidonic acid, or thromboxane. The inhibition occurred at the level of both the cyclooxygenase activity and thromboxane receptor site. Interestingly, all the metabolites tested exhibiting the E,Z,E-conjugated triene were active, whereas E,E,Z trienes (as in PD1) or all-trans (E,E,E) trienes were inactive. We conclude that PDX and other oxygenated products from PUFAs of nutritional interest, having the E,Z,E-conjugated triene motif and collectively named poxytrins (PUFA oxygenated trienes), might have antithrombotic potential.
Chen
Ping
P
Université de Lyon, Unité Mixte de Recherche (UMR) 870, Institut National de la Santé et de la Recherche Médicale (INSERM)/Institut National des Sciences Appliquées–Lyon, and UMR 1235, Institut National de Recherche Agronomique, Villeurbanne, France.
Véricel
Evelyne
E
Lagarde
Michel
M
Guichardant
Michel
M
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D007536:Isomerism; D010100:Oxygen / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000378:metabolism; D013931:Thromboxanes / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D003998:Dicarboxylic Acids; D005231:Fatty Acids, Unsaturated; D010975:Platelet Aggregation Inhibitors; D017482:Receptors, Thromboxane; D013931:Thromboxanes; C487679:protectin D1; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen; D000242:Cyclic AMP; D011451:Prostaglandin-Endoperoxide Synthases; D010100:Oxygen