Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation
Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation
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DOI：
10.1096/fj.10-161836
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发表时间：
2011-01-01
期刊：
影响因子：
4.8
通讯作者：
Guichardant, Michel
中科院分区：
文献类型：
--
作者：
Chen, Ping;Vericel, Evelyne;Guichardant, Michel
二十二碳六烯酸（DHA）是海洋脂质的重要组成部分，其抗炎活性与其一些含氧代谢产物有关，例如通过15-脂氧合酶途径产生的神经保护素/保护素D1 [NPD 1/PD 1; 10（R），17（S）-二羟基-二十二碳-4Z，7Z，11 E，13 E，15 Z，19 Z-六烯酸]。然而，DHA的其他代谢产物可以通过这一途径产生，其他具有营养价值的多不饱和脂肪酸（PUFA）也可以被氧化。它们的生物活性仍然未知。利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的几何异构体，先前描述为11 E，13 Z，15 E几何结构，而不是PD 1中的11 E，13 E，15 Z，当由胶原蛋白，花生四烯酸或血栓烷诱导时，在亚微摩尔浓度下抑制血小板聚集。抑制作用发生在环氧合酶活性和血栓素受体位点水平。有趣的是，所有测试的显示E，Z，E-共轭三烯的代谢物都是活性的，而E，E，Z三烯（如在PD 1中）或全反式（E，E，E）三烯是无活性的。我们得出结论，PDX和其他来自PUFA的含氧产物具有营养价值，具有E，Z，E-共轭三烯基序，统称为环氧丙烷（PUFA含氧三烯），可能具有抗血栓形成的潜力。Chen，P.，Vericel，E.，拉加德，M.，Guichardant，M.多不饱和脂肪酸的氧化产物，强力抑制血小板聚集。FASEB J.25，382-388（2011）. www.fasebj.org
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, P., Vericel, 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