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E Véricel

Publications and source records attributed to E Véricel.

At least 19 recordsLinked to original sources
PubMed2003

Pathophysiologic role of redox status in blood platelet activation. Influence of docosahexaenoic acid.

Decrease of platelet glutathione peroxidase activity results in increased life span of lipid hydroperoxides, especially the 12-lipoxygenase product of arachidonic acid, 12-HpETE. Phospholipase A2 activity is subsequently enhanced with the release of arachidonic acid, which results in higher thromboxane formation and platelet function. Docosahexaenoic acid may either potentiate platelet lipid peroxidation or lower it when used at high or low concentrations, respectively. In the case of slowing down lipid peroxidation, docosahexaenoic acid was specifically incorporated in plasmalogen ethanolamine phospholipids. This could have a relevant pathophysiologic role in atherothrombosis.

Arachidonate 12-Lipoxygenase↗
PubMed2003

Pro- and antioxidant activities of docosahexaenoic acid on human blood platelets.

n - 3 polyunsaturated fatty acids may protect against vascular diseases, however, their high accumulation in membranes may increase lipid peroxidation and subsequently induce deleterious effects in patients suffering from oxidative stress. This led us to investigate in vitro the dose-dependent effect of docosahexaenoic acid (DHA) on the redox status of human platelets. We have compared the effect of different DHA concentrations (0.5, 5 and 50 micro mol L(-1)) corresponding to DHA/albumin ratios of 0.01, 0.1 and 1. At the highest concentration, DHA elicited a marked oxidative stress, as evidenced by high malondialdehyde and low vitamin E levels whereas the lowest DHA concentration significantly decreased the malondialdehyde formation, with no change in vitamin E. The proportion of DHA was only increased in plasmalogen phosphatidylethanolamine at low concentration to rise in all phosphatidyl-choline and -ethanolamine subclasses at high concentration. Thus, the results show a biphasic effect of DHA with antioxidant and prooxidant effects at low and high concentrations, respectively, with a possible relationship with the phospholipid subclass in which it accumulates.

Blood Platelets↗
PubMed2001

Dual regulation of glutathione peroxidase by docosahexaenoic acid in endothelial cells depending on concentration and vascular bed origin.

Docosahexaenoic acid (DHA) has been reported to elicit oxidative stress, which in turn can induce antioxidant enzymes. Glutathione peroxidase (GPx) has received particular attention in this respect, as this enzyme is specifically required for the degradation of lipid hydroperoxides. Because we previously found that DHA could protect against oxidative stress when used in low amounts, we have compared the effect of a low (10 microM) versus high (100 microM) concentration of DHA on oxidant/antioxidant balance in bovine retinal and bovine aortic endothelial cells (BREC and BAEC). At 100 microM, DHA elicited a marked oxidative stress, as evidenced by high malondialdehyde levels and decreased plasmalogen phosphatidylethanolamine in both cells, and for BAEC only, a decrease of alpha-tocopherol. At 10 microM, DHA induced a slight increase of malondialdehyde in both cells, but did not affect alpha-tocopherol levels, which is indicative of a mild oxidative stress. In BREC, 10 microM DHA slightly but significantly decreased cytosolic GPx (cGPx) activity whereas 100 microM had no effect. In contrast, in BAEC, DHA 10 microM did not affect cGPx activity, whereas 100 microM increased it. The decreased cGPx activity in BREC was associated with a lower level of protein, suggesting a transcriptional and/or posttranscriptional effect. Phospholipid hydroperoxide GPx (PHGPx) activity was not modified by DHA at either concentration in BREC, whereas it was increased in BAEC when using 100 microM. Our results confirm that large amounts of DHA lead to oxidative stress, but do no support an antioxidant action of DHA at low concentration, in endothelium. Nevertheless, we showed that DHA can exert opposite effects on GPx regulation in endothelial cells, with regard to its concentration and to vascular bed origin.

Animals↗
PubMed2001

12(S)-Hydroperoxy-eicosatetraenoic acid increases arachidonic acid availability in collagen-primed platelets.

Lipid hydroperoxides have been reported to regulate cell function and eicosanoid formation. The aim of the present study was to determine the effect of 12(S)-hydroperoxy-eicosatetraenoic acid [12(S)-HPETE], the platelet 12-lipoxygenase-derived hydroperoxide of arachidonic acid (AA), on the availability of nonesterified AA, which represents a rate-limiting step in the biosynthesis of eicosanoids. The coincubation of human platelets with concentrations of 12(S)-HPETE below 50 nM and subthreshold concentrations (STC) of collagen (less than 0.24 microg/ml) significantly enhanced platelet aggregation and the formation of thromboxane B(2), the stable catabolite of the potent aggregating agent thromboxane A(2). In addition, the nonesterified endogenous AA concentration increased by 3-fold. Arachidonoyl-containing molecular species concentrations of 1,2-diacyl-glycero-3-phosphocholine, 1-alkyl-2-acyl-glycero-3-phosphocholine, and 1-alkenyl-2-acyl-glycero-3-phosphoethanolamine decreased specifically in response to 12(S)-HPETE, whereas no significant changes were observed within 1,2-diacyl-glycero-3-phosphoethanolamine and 1,2-diacyl-glycero-3-phosphoinositol molecular species. The 12(S)-HPETE-induced increase in nonesterified AA was fully prevented by arachidonoyl trifluoromethyl ketone, an inhibitor of cytosolic phospholipase A(2) (cPLA(2)), and cPLA(2) was translocated to membranes and phosphorylated in platelets incubated with 12(S)-HPETE. In conclusion, these results indicate that nanomolar concentrations of 12(S)-HPETE could play a significant role in controlling the level of endogenous AA and the formation of thromboxane, thereby potentiating platelet function.

Arachidonic Acid↗
PubMed1999

The influence of low intake of n-3 fatty acids on platelets in elderly people.

A total of ten healthy elderly subjects ingested one capsule of 600 mg (corresponding to 150 mg docosahexaenoic acid and 30 mg eicosapentaenoic acid) RO-PUFA triglycerides per day and ten others ingested one capsule of 600 mg sunflower oil as a placebo for 42 days. In the n-3 polyunsaturated fatty acids (PUFA) group, a significant decrease of systolic blood pressure was observed, as well as a trend towards a decrease in both platelet activation and basal formation of thromboxane B(2). Also, a slight but significant increase of docosahexaenoic acid was observed in the phosphatidylethanolamine fraction as well as a significant increase of vitamin E level after the n-3 PUFA intake. Moreover, the basal production of malondialdehyde significantly decreased. No modification was observed for all these parameters in the placebo group. We conclude that a small intake of n-3 PUFA decreased the oxidative stress in platelets of elderly people and could be beneficial in subjects with atherothrombotic tendencies by lowering the cell peroxide tone.

Aged↗
PubMed1997

Effects of fatty acids on human platelet glutathione peroxidase: possible role of oxidative stress.

Highly polyunsaturated fatty acids of the n-3 family are known to be inhibitors of platelet functions, but these fatty acids (FA) may alter the platelet antioxidant status, depending on their concentrations. The present study was aimed to investigate the effect of various FA on glutathione-dependent peroxidase (GPx), the required antioxidant enzyme for degrading FA hydroperoxides. Human platelets were enriched in vitro with either n-3 (18:3, 20.5, or 22.6), n-6 (18:2 or 18:3) FA, 18:1 n-9 or 16:0, and the GPx activity was then measured. It was found that n-3 FA enhanced the GPx activity whereas the others did not affect the enzyme activity. The increased GPx activity was associated with an increased amount of the enzyme measured by Western blotting. The enhanced activity and amount of GPx induced by 22:6n-3, the most potent activator among the n-3 FA, was completely abolished in the presence of cycloheximide at a concentration known to inhibit platelet protein synthesis. Because platelets are devoid of nucleus, which rules out the involvement of transcriptional factors, this suggests that 22:6n-3 might act at a translational level. On the other hand, 22:6n-3 treatment increased the malondialdehyde formation and decreased the vitamin E level in platelets, both events that could be prevented by the antioxidant epicatechin. Because epicatechin also suppressed the enhancement of both the activity and amount of GPx induced by 22:6n-3, we conclude that the increased GPx activity (possibly via protein synthesis) might be associated with an oxidative stress induced by 22:6n-3 and/or 20:4n-6 released from the platelet endogenous pool in the course of the 22:6n-3 enrichment.

Blood Platelets↗
PubMed1997

Involvement of lipid peroxidation in platelet signalling.

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 A2 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.

Aged↗
PubMed1996

N-3 fatty acid-induced lipid peroxidation in human platelets is prevented by catechins.

The effects of catechins were studied in both unstimulated platelets and platelets submitted to a mild oxidative stress induced by docosahexaenoic acid (DHA). Human unstimulated platelets were incubated in the presence of catechin or epicatechin (1, 10 or 100 microM) for 2 h at 37 degrees C. Treatment by 1 microM epicatechin was sufficient to induce a significant inhibition (-30%) of basal thromboxane B2 formation. This result is consistent with the observed inhibitory effects of flavonoids on platelet aggregation. DHA treatment of platelets decreased the amount of alpha-tocopherol and increased the malondialdehyde (MDA) formation. The presence of epicatechin or catechin prevented the oxidative stress induced by DHA. Indeed, the platelet alpha-tocopherol level was significantly increased when compared to that of platelets treated by DHA alone, to reach the control level, whereas MDA was depressed to a level even lower than the control one. Our results indicate that catechin and especially epicatechin protect platelets from a peroxidative stress.

Blood Platelets↗
PubMed1995

Cross-reactivity of delta 17-6-keto-PGF1 alpha with 6-keto-PGF1 alpha antibodies.

The cross-reactivity of the PGI3 metabolite, delta 17-6-keto-PGF1 alpha, with antibodies against 6-keto-PGF1 alpha for radioimmunoassays (RIA) has been investigated. Delta 17-6-keto-PGF1 alpha was obtained either from commercial sources or after its purification from endothelial cells. In the latter case, primary cultured bovine aortic endothelial cells were incubated for 20 min at 37 degrees C with 10 microM eicosapentaenoic acid (EPA) in the presence of 2 microM 13-hydroperoxy-octadecadienoic acid, and activator of the EPA cyclooxygenation, and the 6-keto-PGF1 alpha and beta 17-6-keto-PGF1 alpha produced were separated by RP-HPLC. Then, cross-reactivities of the commercial and purified beta 17-6-keto-PGF1 alpha with 6-keto-PGF1 alpha antibodies were determined and found not to exceed 10%. In addition, the amounts of prostacyclin-related compounds detected by direct measurements in media of cells loaded with EPA were compared with those obtained after purification of 6-keto-PGF1 alpha. In accordance with the cross-reactivity data, we found that RIA in media mainly measured 6-keto-PGF1 alpha, the beta 17-6-keto-PGF1 alpha formed being undetected at 90%. It is concluded that 6-keto-PGF1 alpha antibodies generally used for RIA of 6-keto-PGF1 alpha are highly specific since they can discriminate a metabolite bearing an additional double band such as the PGI3 metabolite beta 17-6-keto-PGF1 alpha.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Age-related changes in linoleic acid bioconversion by isolated hepatocytes from spontaneously hypertensive and normotensive rats.

This study points out the hepatocyte interconversion of the linoleic acid family during hypertension. Hepatocyte delta 6 desaturase activity was higher in 1 month-old spontaneously hypertensive rats than in normotensive controls. A similar tendency was observed in 6 month-old SHR. delta 5 desaturase activity was higher only in 1 month-old spontaneously hypertensive rats as compared to controls. Desaturase activities were particularly high at the age of 6 months. The hepatocyte fatty acid composition showed an impairment of n-6 polyunsaturated fatty acid metabolism in spontaneously hypertensive animals. Changes were greater in the young prehypertensive rats than in adults. A storage of n-3 long chain fatty acids is remarkable in adult hypertensive rats, suggesting an alteration in peroxisomal oxidation. Such modifications may be related to the prostaglandin precursors availability to peripheral tissues such as kidney.

Aging↗
PubMed1994

Purification and characterization of glutathione peroxidase from human blood platelets. Age-related changes in the enzyme.

Platelet glutathione peroxidase (GPx) is known to play a pivotal role in controlling the level of lipid hydroperoxides, especially those resulting from the 12-lipoxygenase activity. GPx was purified from the cell cytosol by more than 700-fold using an exchange chromatography, FPLP, gel filtration and covalent fixation. Isoelectric focusing revealed a peak activity at pH 5.1. The molecular mass of the enzyme was found between 90 and 100 kDa by gel filtration, and was approximating at 23 kDa by SDS-PAGE. A polyclonal antibody raised against commercial bovine erythrocyte GPx recognized the human platelet enzyme. It is concluded that human platelet GPx is likely a homotetramer of 92 kDa as described for most other sources. We have also found that the decreased platelet GPx activity observed in platelets from elderly people is associated with a lower content of the immunoreactive enzyme.

Adult↗
PubMed1994

Age-related changes in antioxidant defence mechanisms and peroxidation in isolated hepatocytes from spontaneously hypertensive and normotensive rats.

The effects of age and hypertension on the antioxidant defence systems and the lipid peroxidation in rat isolated hepatocytes were studied. Four different age groups (1, 3, 6 and 12 months) were considered in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Age-associated changes were observed on vitamin E status, glutathione (GSH) level, MDA formation and glutathione peroxidase (GSH-Px) activity in both strains. Maximal levels or activities of these parameters were found at 3 and 6 months, except for MDA which was low at 3 months. Then, a fall was observed at 12-month-old compared to 6-month values. In addition, GSH-Px activity was significantly lower in SHR than in WKY rats, except at the age of one month. The decrease of this enzyme activity could induce an increased cellular generation of radical species and lipid peroxidation, which might be link to hypertension.

Aging↗
PubMed1993

Variations in the fatty acid composition of lipid classes from lipoproteins in elderly women.

Fatty acid composition of lipid classes and NMR spectra of lipoproteins were compared in 6 young (24-35-year-old) and 6 elderly (79-90-year-old) women. Cholesteryl ester, triglyceride and protein content of LDL in elderly women were significantly higher (+52-57% and +20% for lipids and proteins, respectively) than those observed in young women. HDL lipid levels were similar in the two groups. The proportion of linoleic acid (mainly in cholesteryl esters and phospholipids) of each lipoprotein species was always lower in octogenarians when compared with young females (lowering of 13-28% and 27-46% for cholesteryl esters and phospholipids, respectively). Conversely, the proportions of mono-unsaturated fatty acids (mainly oleic acid) increased in all lipid classes, although this was only significant in cholesteryl esters from each lipoprotein species. NMR spectra of lipoproteins showed a restricted mobility of acyl chain terminal CH3 groups in old women which was significant only in VLDL and HDL3. This suggests that the decrease of linoleic acid could affect the lipid mobility in lipoproteins of elderly women.

Adult↗
PubMed1993

Interactions between arachidonic and eicosapentaenoic acids during their dioxygenase-dependent peroxidation.

Eicosapentaenoic acid (EPA), a major polyunsaturated fatty acid of fish has been widely proposed as a potential nutrient for decreasing platelet-endothelial cell interactions and the subsequent atherogenesis and thrombogenesis. This is mainly based upon the decrease of arachidonic acid (AA) oxygenation into bioactive molecules like thromboxane A2. In addition, EPA may be oxygenated into its own active derivatives via cell dioxygenases. We report evidence for the requirement of specific peroxides, adequately provided by AA, to allow EPA to be oxygenated into its bioactive products like prostaglandin I3, a prostacyclin mimetic. On the other hand, we present some data that argue for a decreased basal AA dioxygenation (specific peroxidation) by small concentrations of EPA. The interactions between AA and EPA are then dual, EPA being able to counteract AA oxygenation whereas EPA requires AA to be efficiently oxygenated.

Aged↗