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
May 1, 1997·European Journal of Biochemistry·A G Börsch-HauboldS P Watson
Jul 10, 1998·Biochemistry·P J LuC S Chen
Sep 9, 2000·The Journal of Biological Chemistry·Y HefnerM H Gelb
Feb 7, 2001·Blood·R BobeS P Watson
May 3, 2002·Blood·Soochong KimSatya P Kunapuli
Sep 28, 2002·Blood·Sheila R HassockKalwant S Authi
May 6, 2003·Blood·Katsue Suzuki-InoueSteve P Watson
Sep 15, 2004·Biochemistry·Ping-Hui TsengChing-Shih Chen
Sep 11, 2007·Blood·Ingeborg Hers
Dec 18, 2007·The FEBS Journal·Paola E J van der MeijdenJohan W M Heemskerk
Oct 4, 2008·Blood·Attila BraunBernhard Nieswandt
Feb 28, 2009·Blood·Kalwant S Authi
May 9, 2009·Journal of Thrombosis and Haemostasis : JTH·D Varga-SzaboB Nieswandt
Jun 12, 2009·Blood·Ilaria CanobbioMauro Torti
Jul 10, 2009·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Nidhal Ben AmorAghleb Bartegi
Jan 13, 2010·Blood·Valérie MartinMarie-Pierre Gratacap
Mar 31, 2010·Expert Review of Hematology·Donna S Woulfe
Dec 21, 2010·Cell Calcium·J A Rosado
Jul 12, 2011·Cell Calcium·Matthew T Harper, Alastair W Poole
Jun 30, 2012·Journal of Thrombosis and Haemostasis : JTH·M P Mahaut-Smith
Aug 8, 2012·Blood·Julia M BurkhartRené P Zahedi
Oct 16, 2012·Cell·Xiang WangHaoxing Xu
Citations
Nov 15, 2017·PloS One·Maria E Lopes PiresJonathan M Gibbins
Jan 20, 2017·American Journal of Physiology. Cell Physiology·Peng-Yuan WangJaladanki N Rao
Apr 6, 2018·International Journal of Molecular Medicine·Gaoyu CaiYi Fu