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Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation
Author(s) -
Chen Ping,
Vãricel Evelyne,
Lagarde Michel,
Guichardant Michel
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-161836
Subject(s) - polyunsaturated fatty acid , chemistry , lipoxygenase , antithrombotic , docosahexaenoic acid , biochemistry , platelet , conjugated system , arachidonic acid , thromboxane a2 , cyclooxygenase , fatty acid , stereochemistry , receptor , enzyme , medicine , organic chemistry , polymer
Docosahexaenoic acid (DHA), an important component of marine lipids, exhibits antiinflammatory 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,19Zhexaenoic 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, arachi‐donic acid, or thromboxane. The inhibition occurred at the level of both the cyclooxygenase activity and throm‐boxane 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‐írαn* ( 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, P., Vãricel, E., Lagarde, M., Guichardant, M. Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation. FASEB J. 25, 382–388 (2011). www.fasebj.org