Studies on topological distribution of arachidonic acid replacement in platelet phospholipids and on enzymes involved in the phospholipid effect accompanying platelet activation

1981 ◽  
Vol 11 (6-7) ◽  
pp. 538-540 ◽  
Author(s):  
H. Chap ◽  
G. Mauco ◽  
B. Perret ◽  
M. Plantavid ◽  
F. Laffont ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Activation

Abstract 492: Arachidonic Acid Induces Activation of Platelet PF4 and Par-1 mRNA, Which Is Attenuated by Aspirin

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Liang Hu ◽  
Michael A Nardi ◽  
Michael Merolla ◽  
Yajaira Suarez ◽  
Jeffrey Berger
Keyword(s):  
Arachidonic Acid ◽  
Platelet Activation ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Thiazole Orange ◽  
Platelet Activity ◽  
Protein Levels ◽  
Reticulated Platelets ◽  
Mrna And Protein Expression ◽  
Dose Dependent

Arachidonic acid (AA) is converted to thromboxane A2 via the cyclooxygenase pathway; however its exact mechanism of platelet activation is uncertain. Inhibition of this pathway via aspirin highlights the importance of this pathway in decreasing thrombotic events. In the present study, we investigate the effect of AA on platelet activity indicators (leukocyte- and monocyte-platelet aggregation [LPA, MPA] and reticulated platelets [RP]), as well as the expression (mRNA and protein) of platelet markers PF4 and Par-1, previously well established platelet transcripts with quantitative determinations. To this end, whole blood was incubated with AA (150mM) for 30 min at room temperature in the absence or presence of aspirin (1mM) prior to addition of antibodies for platelet activity indicators, and isolating platelets for mRNA and protein expression. LPA and MPA were significantly increased after AA stimulation in a dose dependent manner, and were inhibited by aspirin treatment. AA significantly increased PF4 and Par-1 protein level as determined by flow cytometry and western blot assays. Pretreatment with aspirin also attenuated this increase in protein levels. Surprisingly, AA stimulation significantly increased thiazole orange staining (a measure of nucleic acids), another marker of increased platelet activity. Importantly, these results suggest that AA-mediated platelet activation produced an overall increase in platelet total RNA content. To confirm these findings, we analyzed the mRNA expression of PF4 and Par-1 by quantitative real time PCR from platelets treated with AA. Interestingly, AA significantly up-regulated the platelet mRNA transcripts of PF4 and Par-1 by 40% to 60%, and pretreatment with aspirin completely attenuated this effect supporting the specificity of the AA effect on platelet RNA. Altogether, these data suggest that platelet mRNA is affected by AA stimulation, which is attenuated by pretreatment with aspirin. However, the mechanisms responsible for the increased mRNA levels and expression of PF4 and Par-1 (processing of pre-RNA to mRNA) require further investigation. Importantly, our findings provide novel insight regarding platelet activation and a better understanding of mediators in the processes of thrombosis and hemostasis.

Influence of Platelet Activation on Erythrocyte Deformability

1983 ◽  
Vol 49 (02) ◽  
pp. 084-086 ◽  
Author(s):  
W Palinski ◽  
A Torsellini ◽  
L Doni
Keyword(s):  
Arachidonic Acid ◽  
Acetylsalicylic Acid ◽  
Platelet Activation ◽  
Platelet Rich Plasma ◽  
Plasma Viscosity ◽  
Erythrocyte Deformability ◽  
Direct Influence ◽  
Antagonistic Action ◽  
Malondialdehyde Formation ◽  
Autologous Platelet

SummaryErythrocyte deformability was demonstrated to be influenced by platelet activation. Deformability of erythrocytes suspended in autologous platelet poor plasma (PPP), obtained from platelet rich plasma (PRP), was significantly reduced when PRP had previously been incubated with a platelet activating substance (arachidonic acid, adrenaline or ADP). The possibility of a direct influence of the activating substance on erythrocyte deformability was examined and malondialdehyde formation was determined as an indicator of platelet activation. Erythrocyte deformability was not impaired when endoperoxide formation in platelets was blocked by an inhibitor of cyclooxigenase (acetylsalicylic acid). Plasma viscosity was not influenced by platelet activation as demonstrated by filtration and viscosimetry. Recent studies showed that prostacyclin (PGI2) increases erythrocyte deformability (1). The antagonistic action between prostacyclin released by vessel walls and products of platelet metabolism being well known, we discuss possible mechanisms of this effect and pathophysiological relevance of our results.

Evidence for a Role for Phospholipase C, but not Phospholipase A2, in Platelet Activation in Response to Low Concentrations of Collagen

2001 ◽  
Vol 85 (05) ◽  
pp. 882-889 ◽  
Author(s):  
Leslie Lockhart ◽  
Caroline Pampolina ◽  
Brent Nickolaychuk ◽  
Archibald McNicol
Keyword(s):  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Phospholipase C ◽  
Platelet Activation ◽  
Cytosolic Phospholipase A2 ◽  
Arachidonic Acid Release ◽  
Cytosolic Phospholipase ◽  
Low Concentrations ◽  
Acid Release ◽  
Induced Aggregation

SummaryThe release of arachidonic acid is a key component in platelet activation in response to low concentrations (1-20 g/ml) of collagen. The precise mechanism remains elusive although a variety of pathways have been implicated. In the present study the effects of inhibitors of several potentially key enzymes in these pathways have been examined. Collagen (1-10 g/ml) caused maximal platelet aggregation which was accompanied by the release of arachidonic acid, the synthesis of thromboxane A2, and p38MAPK phosphorylation. Preincubation with the dual cyclooxygenase/lipoxygenase inhibitor BW755C inhibited aggregation and thromboxane production, and reduced p38MAPK phosphorylation. A phospholipase C inhibitor, U73122, blocked collagen-induced aggregation and reduced arachidonic acid release, thromboxane synthesis and p38MAPK phosphorylation. Pretreatment with a cytosolic phospholipase A2 inhibitor, AACOCF3, blocked collagen-induced aggregation, reduced the levels of thromboxane formation and p38MAPK phosphorylation but had no significant effect on arachidonic acid release. In contrast inhibition of PKC by Rö31-8220 inhibited collagen-induced aggregation, did not affect p38MAPK phosphorylation but significantly potentiated arachidonic acid release and thromboxane formation. Collagen caused the tyrosine phosphorylation of phospholipase C 2 which was inhibited by pretreatment with U73122, unaffected by AACOCF3 and enhanced by Rö31-8220. These results suggest that cytosolic phospholipase A2 plays no role in the arachidonic acid release in response to collagen. In contrast, the data are consistent with phospholipase C 2 playing a role in an intricately controlled pathway, or multiple pathways, mediating the release of arachidonic acid in collagen-stimulated platelets.

A role for p38 MAP kinase in platelet activation by von Willebrand Factor

2004 ◽  
Vol 91 (01) ◽  
pp. 102-110 ◽  
Author(s):  
Ilaria Canobbio ◽  
Stefania Reineri ◽  
Fabiola Sinigaglia ◽  
Cesare Balduini ◽  
Mauro Torti
Keyword(s):  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Map Kinase ◽  
Platelet Activation ◽  
Von Willebrand Factor ◽  
P38 Map Kinase ◽  
Cyclooxygenase Inhibitors ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Stimulation Of

SummaryPlatelet activation induced by von Willebrand factor (VWF) binding to the membrane GPIb-IX-V receptor involves multiple signal transduction pathways. Among these, recruitment and activation of the FcγRIIA and stimulation of phospholipase A2 represent independent events equally essential to support a complete platelet response. Phospholipase A2 is activated by calcium and by phosphorylation through MAP kinases. In this work, we found that VWF stimulated the rapid and sustained phosphorylation of p38 MAP kinase (p38MAPK). In vitro kinase assay revealed that VWF-stimulated phosphorylation of p38MAPK was associated with increased kinase activity. Binding of VWF to GPIb-IX-V, but not to integrin αIIbβ3, was required to support phosphorylation of p38MAPK. Neither the blockade of the membrane FcγRIIA by a specific monoclonal antibody or the prevention of thromboxane A2 synthesis by cyclooxygenase inhibitors affected VWF-induced p38MAPK activation. However, phosphorylation of p38MAPK was prevented by the tyrosine kinase Syk inhibitor piceatannol. Treatment of platelets with the p38MAPK inhibitor SB203580 totally prevented VWFstimulated platelet aggregation. Moreover, release of arachidonic acid induced by VWF was strongly impaired by inhibition of p38MAPK. We also found thatVWF induced phosphorylation of cytosolic phospholipase A2, and that this process was prevented by the p38MAPK inhibitor SB203580.These results demonstrate that p38MAPK is a key element in the FcγRIIA-independent pathway for VWF-induced platelet activation, and is involved in the stimulation of phospholipase A2 and arachidonic acid release.

Hyperaggregability Of Serotonin-Depleted Platelets To Arachidonic Acid (AA) In SLE And Transplant Recipients

1981 ◽  
Author(s):  
D Marchesi ◽  
A Parbtani ◽  
G Frampton ◽  
M Livio ◽  
G Remuzzi ◽  
...  
Keyword(s):  
Renal Function ◽  
Arachidonic Acid ◽  
Nephrotic Syndrome ◽  
Platelet Activation ◽  
Great Majority ◽  
Transplant Recipients ◽  
Renal Microvasculature ◽  
Thrombotic Tendency ◽  
Reduced Renal Function

In a variety of renal disorders, including SLE and transplantation, in vivo platelet activation is present. This is in part a result of the nephrotic syndrome, but is also observed in patients with g.n. who are not nephrotic. As a result, intraplatelet concentrations of serotonin and other amines are depleted in patients with active nephritis. The functional capacity of such amine-depleted platelets has been little studied; Pareti et al (1980) reported defective aggregation to ADP, adrenaline and collagen in such “acquired storage pool deficiencies”. We studied aggregation thresholds to ADP, collagen and AA in 25 patients with SLE nephritis, none of whom had a nephrotic syndrome or reduced renal function. In these patients platelet activation is due principally to circulating factors. Sixteen transplant recipients were also studied. In them, activation is principally within the renal microvasculature of the allograft. We also measured intraplatelet serotonin concentrations, which were low or zero in the great majority of patients in both groups. Bleeding times were normal in all, as were platelet aggregation thresholds to ADP and collagen. AA thresholds, however, were markedly depressed (<0.32 mmol) in all transplant recipients and most patients with SLE. This specific hyperaggregability may be responsible for both persistence of disease and the thrombotic tendency observed in some patients, including those with circulating anticoagulant.

scholarly journals Effect of alteplase on platelet function and receptor expression

2019 ◽  
Vol 47 (4) ◽  
pp. 1731-1739 ◽  
Author(s):  
Jun Lu ◽  
Peng Hu ◽  
Guangyu Wei ◽  
Qi Luo ◽  
Jianlin Qiao ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Activation ◽  
Platelet Function ◽  
Adenosine Diphosphate ◽  
Receptor Expression ◽  
Light Transmittance ◽  
Dependent Manner ◽  
Clot Retraction ◽  
Platelet Receptors

Objective To investigate the role of alteplase, a widely-used thrombolytic drug, in platelet function. Methods Human platelets were incubated with different concentrations of alteplase followed by analysis of platelet aggregation in response to adenosine diphosphate (ADP), collagen, ristocetin, arachidonic acid or epinephrine using light transmittance aggregometry. Platelet activation and surface levels of platelet receptors GPIbα, GPVI and αIIbβ3 were analysed using flow cytometry. The effect of alteplase on clot retraction was also examined. Results This study demonstrated that alteplase significantly inhibited platelet aggregation in response to ADP, collagen and epinephrine in a dose-dependent manner, but it did not affect ristocetin- or arachidonic acid-induced platelet aggregation. Alteplase did not affect platelet activation as demonstrated by no differences in P-selectin levels and PAC-1 binding being observed in collagen-stimulated platelets after alteplase treatment compared with vehicle. There were no changes in the surface levels of the platelet receptors GPIbα, GPVI and αIIbβ3 in alteplase-treated platelets. Alteplase treatment reduced thrombin-mediated clot retraction. Conclusions Alteplase inhibits platelet aggregation and clot retraction without affecting platelet activation and surface receptor levels.

scholarly journals Secretory phospholipase A2 is not required for arachidonic acid liberation during platelet activation

1993 ◽  
Vol 216 (1) ◽  
pp. 169-175 ◽  
Author(s):  
Carine MOUNIER ◽  
Ahmad FAILI ◽  
B. Boris VARGAFTIG ◽  
Cassian BON ◽  
Mohamed HATMI
Keyword(s):  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Platelet Activation ◽  
Secretory Phospholipase A2 ◽  
Secretory Phospholipase

Effect of Oestrogen Dose on Whole Blood Platelet Activation in Women Taking New Low Dose Oral Contraceptives

1994 ◽  
Vol 72 (06) ◽  
pp. 926-930 ◽  
Author(s):  
Lucy A Norris ◽  
John Bonnar
Keyword(s):  
Arachidonic Acid ◽  
Oral Contraceptive ◽  
Platelet Activation ◽  
Oral Contraceptives ◽  
Whole Blood ◽  
Contraceptive Use ◽  
Blood Platelet ◽  
Individual Treatment ◽  
Oral Contraceptive Use ◽  
Induced Aggregation

SummaryOral contraceptive use is known to cause changes in the haemostatic system. These changes are thought to be related to oestrogen dose and to provide a possible link between the increased risk of thromboembolic disease known to occur in women taking oestrogen containing oral contraceptives. This study measured whole blood platelet activation, serially, in women taking oral contraceptives containing 20 μg and 30 μg ethinyloestradiol combined with desogestrel. Increased levels of ADP and arachidonic acid induced aggregation were observed in women taking the 30 μg ethinyloestradiol combination. Platelet release of β-thromboglobulin (βTG) was also significantly increased. Increased collagen induced aggregation was observed but this failed to reach statistical significance for the individual treatment groups. In women taking the 20 μg ethinyloestradiol combination, a significant increase was only observed when platelets were stimulated with arachidonic acid. Platelet factor 4 (PF4) levels were unchanged in both groups. Significantly higher levels of βTG were observed in women taking the 30 μg ethinyloestradiol combination compared with women taking the 20 μg ethinyloestradiol combination. These results show that oral contraceptive use is associated with platelet activation. Women taking the 20 μg ethinyloestradiol combination show less changes in platelet activation than women taking the 30 μg ethinyloestradiol combination. This lower dose pill may therefore be particularly suitable for high risk women wishing to use oral contraception.

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