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Oxygenation of polyunsaturated fatty acids and oxidative stress within blood platelets

Abstract : The oxygenation metabolism of arachidonic acid (ArA) has been early described in blood platelets, in particular with its conversion into the potent labile thromboxane A2 that induces platelet aggregation and vascular smooth muscle cells contraction. In addition, the primary prostaglandins D2 and E2 have been mainly reported as inhibitors of platelet function. The platelet 12-lipoxygenase (12-LOX) product, i.e. the hydroperoxide 12-HpETE, appears to stimulate platelet ArA metabolism at the level of its release from membrane phospholipids through phospholipase A2 (cPLA2) and cyclooxygenase (COX-1) activities, the first enzymes in prostanoid production cascade. Also, 12-HpETE may regulate the oxygenation of other polyunsaturated fatty acids (PUFA) by platelets, especially that of eicosapentaenoic acid (EPA). On the other hand, the reduced product of 12-HpETE, 12-HETE, is able to antagonize TxA2 action. This is even more obvious for the 12-LOX end-products from docosahexaenoic acid (DHA), 11- and 14-HDoHE. In addition, 12-HpETE plays a key role in platelet oxidative stress as observed in pathophysiological conditions, but may be regulated by DHA with a bimodal way according to its concentration. Other oxygenated products of PUFA, especially omega-3 PUFA, produced outside platelets may affect platelet functions as well.
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Submitted on : Friday, April 6, 2018 - 9:45:56 AM
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Michel Lagarde, Michel Guichardant, Nathalie Bernoud-Hubac, Catherine Calzada, Evelyne Véricel. Oxygenation of polyunsaturated fatty acids and oxidative stress within blood platelets. Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids, Elsevier, 2018, 1863 (6), pp.651-656. ⟨10.1016/j.bbalip.2018.03.005⟩. ⟨inserm-01760167⟩

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