Phosphatidylinositol-3,4,5-trisphosphate stimulates Ca(2+) elevation and Akt phosphorylation to constitute a major mechanism of thromboxane A2 formation in human platelets

Cellular Signalling
Nick KassoufKalwant S Authi

Abstract

Phosphatidylinositol trisphosphate (PIP3) has been implicated in many platelet functions however many of the mechanisms need clarification. We have used cell permeable analogues of PIP3,1-O-(1,2-di-palmitoyl-sn-glyero-3-O-phosphoryl)-D-myo-inositol-3,4,5-trisphosphate (DiC16-PIP3) or 1-O-(1,2-di-octanoyl-sn-glyero-3-O-phosphoryl)-D-myo-inositol-3,4,5-trisphosphate (DiC8-PIP3) to study their effects on activation on washed human platelets. Addition of either DiC8- or DiC16-PIP3 to human platelets induced aggregation in the presence of extracellular Ca(2+). This was reduced by the presence of indomethacin, the phospholipase C inhibitor U73122 and apyrase. DiC8-PIP3 induced the phosphorylation of Akt-Ser(473) which was reduced by the Akt inhibitor IV, wortmannin and EGTA (suggesting a dependence on Ca(2+) entry). In Fura2 loaded platelets DiC8-PIP3 was effective at increasing intracellular Ca(2+) in a distinct and transient manner that was reduced in the presence of indomethacin, U73122 and 2-aminoethyl diphenylborinate (2APB). Ca(2+) elevation was reduced by the non-SOCE inhibitor LOE908 and also by the SOCE inhibitor BTP2. DiC8-PIP3 induced the release of Ca(2+) from stores which was not affected by the proton dissipating agent ...Continue Reading

References

Feb 28, 2009·Blood·Kalwant S Authi
May 9, 2009·Journal of Thrombosis and Haemostasis : JTH·D Varga-SzaboB Nieswandt
Jul 10, 2009·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Nidhal Ben AmorAghleb Bartegi
Mar 31, 2010·Expert Review of Hematology·Donna S Woulfe
Dec 21, 2010·Cell Calcium·J A Rosado
Jun 30, 2012·Journal of Thrombosis and Haemostasis : JTH·M P Mahaut-Smith

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Citations

Jan 20, 2017·American Journal of Physiology. Cell Physiology·Peng-Yuan WangJaladanki N Rao

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