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.
FASEB J. 2011 Jan;25(1):382-8. doi: 10.1096/fj.10-161836. Epub 2010 Sep 10.
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.
二十二碳六烯酸（DHA）是海洋脂质的重要成分，具有抗炎活性，与其一些氧化代谢物有关，如通过 15-脂氧合酶途径产生的神经保护素/保护素 D1[NPD1/PD1；10（R），17（S）-二羟基二十二碳四烯酸]。然而，DHA 还可以通过这条途径产生其他代谢物，其他有营养价值的多不饱和脂肪酸（PUFAs）也可能被氧化。它们的生物活性尚不清楚。使用大豆脂氧合酶合成了保护素 D1 的异构体，并测试了它们抑制人血小板聚集的能力。一种称为 PDX 的立体异构体，以前被描述为 11E、13Z、15E 几何形状，而不是 PD1 中的 11E、13E、15Z，在胶原、花生四烯酸或血栓烷诱导下，以亚微摩尔浓度抑制血小板聚集。抑制作用发生在环加氧酶活性和血栓烷受体部位。有趣的是，所有测试的代谢物都表现出 E、Z、E 共轭三烯活性，而 E、E、Z 三烯（如 PD1 中）或全反式（E、E、E）三烯则没有活性。我们得出结论，PDX 和其他具有 E、Z、E 共轭三烯结构的营养相关多不饱和脂肪酸的氧化产物，统称为 poxytrins（多不饱和脂肪酸氧化三烯），可能具有抗血栓形成的潜力。
