Oxygenation of polyunsaturated fatty acids and oxidative stress within blood platelets (original) (raw)
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Different metabolic behavior of long-chain n-3 polyunsaturated fatty acids in human platelets
Biochimica et biophysica acta, 1988
Whereas numerous studies deal with the effects and metabolism of eicosapentaenoic acid (20:5(n - 3)) in platelets, very few concern docosahexaenoic acid (22:6(n - 3)), although both acids are consumed in equal amounts from most fish fat. The present paper reports the modulation of 22:6(n - 3) oxygenation as well as that of endogenous arachidonic acid (20:4(n - 6)) in 22:6(n - 3)-rich platelets. Like the oxygenation of 20:5(n - 3), the lipoxygenation of 22:6(n - 3) occurred at a low level when incubated alone, but was markedly increased in the presence of 20:4(n - 6), suggesting a similar peroxide tone dependency. 20:5(n - 3) could not replace 20:4(n - 6) in the increasing 22:6(n - 3) lipoxygenation, whereas 22:6(n - 3) shared the potentiating effect of 20:4(n - 6) on both the cyclooxygenation and the lipoxygenation of 20:5(n - 3). On the other hand, 20:5(n - 3), 22:6(n - 3) or 20:5(n - 3) + 22:6(n - 3) enrichment of platelet phospholipids inhibited the formation of cyclooxygenase bu...
Lipids, 1985
Human platelet lipoxygenase activity toward several eicosaenoic acids was measured in intact cells as well as in subcellular fractions (cytosol and membranes). In whole platelets, the lipoxygenation of eicosaenoic acids was enhanced greatly by high concentrations of aspirin, which partially inhibit the peroxidase activity associated with the pathway. The lipoxygenation also was increased by arachidonic acid (AA) or its lipoxygenase product, 12-hydroxyperoxy-eicosatetraenoic acid (12-HPETE). Similarly, prostanoid precursors, dihomogammalinolenic (DHLA) and eicosapentaenoic (EPA) acids also were better converted by cyclooxygenase in the presence of AA or 12-HPETE. Among the eicosaenoic acids tested, EPA oxygenation was affected most. Using cytosol or membranes as the lipoxygenase source instead of whole cells led to completely different results. AA exerted a competitive inhibition upon the other eicosaenoic acid oxygenation except that of EPA, for which a dual effect of AA was observed. This makes questionable the use of platelet subfractions for investigating lipoxygenase activity. We conclude that platelet lipoxygenarion of eicosaenoic acids appears peroxide-dependent, espedally for apparent poor substrates like EPA. This might be relevant in respect to 12-HPETE, which is the main hydroperoxy derivative to be produced during platelet activation.
Dose-effect and metabolism of docosahexaenoic acid: Pathophysiological relevance in blood platelets
Prostaglandins, Leukotrienes and Essential Fatty Acids, 2013
Docosahexaenoic acid (DHA) is known as a major nutrient from marine origin. Considering its beneficial effect in vascular risk prevention, the effect of DHA on blood components, especially platelets, will be reviewed here. Investigating the dose-effect of DHA in humans shows that daily intake lower than one gram/day brings several benefits, such as inhibition of platelet aggregation, resistance of monocytes against apoptosis, and reinforced antioxidant status in platelets and lowdensity lipoproteins. However, higher daily intake may be less efficient on those parameters, especially by losing the antioxidant effect. On the other hand, a focus on the inhibition of platelet aggregation by lipoxygenase end-products of DHA is made. The easy conversion of DHA by lipoxygenases and the formation of a double lipoxygenation product named protectin DX, reveal an original way for DHA to contribute in platelet inhibition through both the cyclooxygenase inhibition and the antagonism of thromboxane A 2 action. Docosahexaenoic acid (DHA) is considered as the major end-product of the omega-3 essential fatty acids starting from the indispensable α-linolenic acid in mammals. The conversion of the latter into the former is supposed to be low in humans, except in pregnant women (1). In addition to be the main polyunsaturated fatty acyl residue in the brain and retinal phospholipids (2), DHA is an important nutrient found in marine food, and it may accumulate in many cells to reach a few percent of membrane phospholipid fatty acyls, including blood cell membranes. It is assumed to play a positive role in preventing the cardiovascular risk (3). This could be due to structural effects, in relation to the folding of the molecule induced by its six cis/Z double bonds (4). Another possibility is to inhibit the conversion of arachidonic acid (ARA) at the level of the cyclooxygenase enzymes (5), then decreasing the formation of the atherothrombotic agent thromboxane (Tx) A 2 from ARA. In addition, DHA is easily oxygenated by lipoxygenases (6,7) and some of their end-products may counteract the effect of TxA 2 on its receptor site (8). After its intake as esterified in triglycerides (fish or algal oil) or in phospholipids (fish meat), DHA is quickly distributed within blood lipoproteins (9) and made available to tissues, including blood cells, where it is transferred for esterification into membrane phospholipids (10,11). The issue of the dose intake in dietary approaches is an important one as some studies have reported that, due to their high number of methylene interrupted double bonds, long-chain omega-3 polyunsaturated fatty acids (PUFA) such as DHA could be prone to peroxidation and could even promote it, depending on the amount ingested (12). The present manuscript addresses both that issue, especially focusing on blood platelets in their plasma environment, and the inhibition of platelet aggregation by lipoxygenase products of DHA.
Involvement of lipid peroxidation in platelet signalling
Prostaglandins, Leukotrienes and Essential Fatty Acids, 1997
A well-known signalling pathway in blood platelets consists in the release of arachidonic acid (AA) from membrane phospholipids and its specific oxygenation into bioactive derivatives. In particular, cyclic prostaglandin endoperoxides and thromboxane A 2 are potent inducers of platelet functions and are produced in greater amounts when the level of lipid hydroperoxides is higher than normal, as 'physiological concentrations' of such peroxides activate the cyclooxygenation of AA. In this context, a lower activity of platelet glutathione peroxidase (GPx), the key-enzyme for the degradation of lipid hydroperoxides, has been reported in aging, which will ensure a longer life span to those peroxides. Accordingly, the biosynthesis of pro-aggregatory prostanoids is elevated in platelets from the elderly. On the other hand, fatty acids from marine origin have been recognized as inhibitors of platelet functions, and they may alter the redox status of cells. They may for instance increase the platelet GPx activity, an effect that can be prevented by antioxidants. Overall, these data point out the relevance of the redox status in platelet functions.
Arachidonic acid metabolism in platelets stored for 5 days
British Journal of Haematology, 1990
Arachidonic acid [(C-I4)-AA] metabolism was studied in platelet concentrates (PCs) stored for 5 d. There was a gradual decrease in uptake of radioactivity from day0 to 3 (P<0.01). Onday 0, distributionofradioactivityin platelet phospholipids (PLs), and formation of phosphatidic acid, HETE and cyclooxygenase. products, when platelets were exposed to thrombin (5 IJ/ml), were similar to that reported for fresh platelets. On day 3 there was a change in the distribution of (C-l4)-AA in platelet PLs which consisted of an increase in the percentage of radioactivity bound to phosphatidylserine. from 5.3 &0.9% on day 0 to 8.8 h 1.5% on day 3 (P<0.001), and a decrease in (C-l4)-AA in phosphatidylinositol (PI), from 12.4f 1.5% on day 0, to 7.9*0.9% on day 3 (P<0.001). Phosphatidic acid generated by thrombin-stimulated platelets on day 0, comprised 2. 6 5 0 5 % of total radioactivity, but dropped to 1.4+0.30/, on day 3 (P<0.001), and 0.9&0.2% on day 5 (P<0.01). These values showed a good correlation with the percentage of (C-I4)-AA released from PI on the same days (r=0.9). On day 0, 13.4 h 4.4% of platelet radioactivity was released from
Lipoxygenase activity of intact human platelets
Prostaglandins, Leukotrienes and Medicine, 1984
The oxygenation by lipoxygenase of different icosaenoic and docosaenoic acids by intact human platelets was studied. The RPLC analysis of the hydroxy compound (8) derived from icosaenoic acids showed that the 12derivatives predominate. The increase of the fatty acid concentration markedly enhanced their oxygenation except for icosapentaenoic acid. The conversion of this acid into its hydroxy derivative rose in the presence of arachidonic acid, probably through both its cycle-oxygenase and lipoxygenase product formation. Since 12-hydroxy-icosaenoic a&ids are modulators of PGH2-induced platelet aggregation, we conclude that the interactions between polyunsaturated fatty acids during their oxygenation by platelet lipoxygenase could be relevant to the regulating activity of dietary fatty acids.