59 Role of phosphatidylinositol 3-kinase in human platelet aggregation

1997 ◽  
Vol 25 (4) ◽  
pp. S600-S600 ◽  
Author(s):  
BUKHTIAR H. SHAH ◽  
SHEIKH A. SAEED ◽  
GAZALA SHAMIM ◽  
ZAFAR NAWAZ ◽  
ANWAR H. GILANI
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Phosphatidylinositol 3 Kinase ◽  
Human Platelet Aggregation ◽  
Phosphatidylinositol 3

Sulforaphane prevents human platelet aggregation through inhibiting the phosphatidylinositol 3-kinase/Akt pathway

2013 ◽  
Vol 109 (06) ◽  
pp. 1120-1130 ◽  
Author(s):  
Wen-Ying Chuang ◽  
Po-Hsiung Kung ◽  
Chih-Yun Kuo ◽  
Chin-Chung Wu
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Thrombus Formation ◽  
Critical Factor ◽  
Underlying Mechanism ◽  
Akt Pathway ◽  
Flow Conditions ◽  
Phosphatidylinositol 3 Kinase ◽  
Human Platelet Aggregation ◽  
Phosphatidylinositol 3

SummarySulforaphane, a dietary isothiocyanate found in cruciferous vegetables, has been shown to exert beneficial effects in animal models of cardiovascular diseases. However, its effect on platelet aggregation, which is a critical factor in arterial thrombosis, is still unclear. In the present study, we show that sulforaphane inhibited human platelet aggregation caused by different receptor agonists, including collagen, U46619 (a thromboxane A2 mimic), protease-activated receptor 1 agonist peptide (PAR1-AP), and an ADP P2Y12 receptor agonist. Moreover, sulforaphane significantly reduced thrombus formation on a collagen-coated surface under whole blood flow conditions. In exploring the underlying mechanism, we found that sulforaphane specifically prevented phosphatidylinositol 3-kinase (PI3K)/Akt signalling, without markedly affecting other signlaling pathways involved in platelet aggregation, such as protein kinase C activation, calcium mobilisation, and protein tyrosine phosphorylation. Although sulforaphane did not directly inhibit the catalytic activity of PI3K, it caused ubiquitination of the regulatory p85 subunit of PI3K, and prevented PI3K translocation to membranes. In addition, sulforaphane caused ubiquitination and degradation of phosphoinositide-dependent kinase 1 (PDK1), which is required for Akt activation. Therefore, sulforaphane is able to inhibit the PI3K/Akt pathway at two distinct sites. In conclusion, we have demonstrated that sulforaphane prevented platelet aggregation and reduced thrombus formation in flow conditions; our data also support that the inhibition of the PI3K/Akt pathway by sulforaphane contributes it antiplatelet effects.

Inhibition of Human Platelet Aggregation by the Proteolytic Effect of Streptokinase Role of the Human Factor-VIII-Related Protein

1976 ◽  
Vol 5 (5) ◽  
pp. 306-317
Author(s):  
Ricardo Castillo ◽  
Santiago Maragall ◽  
Javier Alvarez Guisasola ◽  
Francisco Casals ◽  
Juan Profitós ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Human Factor ◽  
Human Platelet ◽  
Related Protein ◽  
Human Platelet Aggregation ◽  
Human Factor Viii

scholarly journals Role of chondroitin 4-sulphate as a receptor for polycation induced human platelet aggregation

1996 ◽  
Vol 119 (7) ◽  
pp. 1447-1453 ◽  
Author(s):  
José L. Donato ◽  
Sisi Marcondes ◽  
Edson Antunes ◽  
Marie D. Nogueira ◽  
Helena B. Nader ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Human Platelet Aggregation

Superoxide Dismutase Cooperates with Prostacyclin to Inhibit Platelet Aggregation: a Comparative Study in Washed Platelets and Platelet Rich Plasma

1991 ◽  
Vol 65 (04) ◽  
pp. 421-424 ◽  
Author(s):  
Daniela Salvemini ◽  
Gilberto de Nucci ◽  
John R Vane
Keyword(s):  
Superoxide Dismutase ◽  
Platelet Aggregation ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Inhibit Platelet Aggregation ◽  
Relaxing Factor ◽  
Human Platelet Aggregation ◽  
Endothelium Derived Relaxing Factor ◽  
Krebs Buffer

SummaryThe role of superoxide anions (O2 −) in human platelet aggregation in Krebs’ buffer or plasma was investigated. In indome thacin (10 μM)-treated washed platelets superoxide dismutase (SOD; 60 U/ml) or ferricytochrome c (FCC; 70 μM) inhibited platelet aggregation by thrombin but not that by collagen or ADP. In addition, in indomethacin (10 μM)-treated washed platelets, SOD significantly potentiated the anti-aggregatory activity of prostacyclin (PGI2) or iloprost when thrombin but not collagen was used as the aggregating agent. In platelet rich plasma, SOD (60 U/ml) did not inhibit platelet aggregation nor did it potentiate the anti-aggregatory activity of iloprost when ADP, collagen or thrombin were used as aggregating agents. Thus, O2 − participate in the aggregatory activity of thrombin but not collagen or ADP and PGI2 or iloprost, by reducing the sensitivity of platelets to thrombin, co-operate with SOD to inhibit thrombin-induced platelet aggregationThe interpretation of the use of SOD in experiments involving endothelium-derived relaxing factor (NO) is discussed

Human Platelet Aggregation Without Thromboxane (Tx) Formation

1981 ◽  
Author(s):  
J Westwick ◽  
J B Smith ◽  
V V Kakkar
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Human Platelets ◽  
Synthesis Inhibitor ◽  
Thromboxane Receptor ◽  
Human Platelet Aggregation ◽  
Thromboxane Receptor Antagonist ◽  
Induced Aggregation ◽  
Carbocyclic Thromboxane A2

It is not known whether PG endoperoxides have to be converted to TxA2 in order to induce aggregation and secretion We have examined this crucial question by measuring human platelet aggregation, 14C-5HT release and TxB2 formation induced by collagen, arachidonic acid (AA), adrenaline, U46619 and PGH2 in presence of either 1) 1-2-(4-carboxy-phenoxy) ethyl imidazole hydrochloride, a potent and selective thromboxane synthesis inhibitor (TSI) or a carbocyclic thromboxane A2 (CTA) - a so called thromboxane receptor antagonist. TSI, 1.5 to 75μM produced a dose related inhibition (IC50 5μM n=5) of Tx and elevation of PGE2 synthesis in adrenaline (8μM) and collagen (1.5μg/ml) stimulated platelets. When 14C-SHT labelled platelets were stimulated with 4.5μM adrenaline in the presence of 0, 2.5, 15 and 300μM TSI a 35±2.8, 27±0.5, 24.5±5.0% release of 14C-5HT release resulted and a 10014, 9612, 9711 and 9114% of control aggregation occurred. Similarly when human platelets were stimulated with 0.8mMAA a 51±1.4% (mean ±SE) release of 14C-5HT occurred, while in the presence of 15, 75 and 300μM of UK, a 42±0.4, 32±1, 33±3% of 14C-5HT release resulted. Aggregation induced by the PG endoperoxide analogue U46619 (lμM) was not inhibited by 300μM TSI or l00μM indomethacin, although 99.5% inhibition of Tx formation resulted, and 50 to 60% inhibition of 14C-5HT release was produced both by TSI and indomethacin. However CTA (l-3±M) produced a dose related inhibition of both aggregation and release induced by U46619. CTA (l-10μM) was found to produce superimposable dose related inhibition of collagen induced aggregation and secretion of platelets, whether the platelets were pretreated with 300μM TSI, or not.These results suggest that Tx formation is not necessary for human platelet aggregation, although is contributory to 14C-5HT release induced by collagen, adrenaline, AA and U46619.Also caution must be employed when CTA is used to elucidate the role of TxA2, as it appears to be an effective PG endoperoxide antagonist.

Effect of nitroxyl on human platelets function

2005 ◽  
Vol 94 (09) ◽  
pp. 578-584 ◽  
Author(s):  
Emilse Bermejo ◽  
Fabiana Alberto ◽  
Ruth E. Rosenstein ◽  
Sara E. Bari ◽  
María A. Lazzari ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Functional Role ◽  
Human Platelet ◽  
Atp Release ◽  
Human Platelets ◽  
Angeli's Salt ◽  
Human Platelet Aggregation ◽  
Platelets Function ◽  
Platelet Physiology

SummaryThere is a growing body of evidence on the role of nitric oxide (NO) in human platelet physiology regulation. Recently, interest has developed in the functional role of an alternative redox form of NO, namely nitroxyl (HNO/NO-), because it is formed by a number of diverse biochemical reactions. The aim of the present study was to comparatively analyze the effect of HNO and NO on several functional parameters of human platelets. For this purpose, sodium trioxodinitrate (Angeli’s salt, AS) and sodium nitroprusside (SNP) were used as HNO and NO releasers, respectively. Both AS and SNP significantly inhibited platelet aggregation and ATP release induced by different agonists and adrenaline. AS or SNP did not modify the expression of platelet glycoproteins (Ib, IIb-IIIa, Ia-IIa, IV), whereas they substantially decreased the levels of CD62P, CD63 and of PAC-1 (a platelet activated glycoprotein IIb/IIIa epitope) after the stimulation with ADP. AS and SNP significantly increased cGMP accumulation in a 1H-[1,2,4]oxadiazolo [4,3-a] quinoxalin-1-one (ODQ)-sensitive manner. However, while L-cysteine reduced the effect of AS, it increased the effect of SNP on this parameter. Accordingly, a differential effect of L-cysteine was observed on the antiaggregatory effect of both compounds. In summary, these results indicate that HNO is an effective inhibitor of human platelet aggregation.

Sign in / Sign up

Export Citation Format

Share Document