Priming of platelet α(IIb)β3 by oxidants is associated with tyrosine phosphorylation of β3

Kaikobad Irani, Youm Pham, Lindsay D. Coleman, Christine Roos, Glen E. Cooke, Amir Miodovnik, Nayeem Karim, Calvin C. Wilhide, Paul F. Bray, Pascal J. Goldschmidt-Clermont

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Reactive oxygen species play an important role at the site of vascular injuries and arterial thromboses. We studied the mechanism mediating platelet aggregation induced by H2O2, a major cellular oxidant. Exposure to H2O2 triggered platelet aggregation, but only when the platelets were stirred. Strong platelet aggregation induced by H2O2 required the presence of the tyrosine phosphatase inhibitor sodium orthovanadate (NaVO4) and was dependent on the participation of integrin α(IIb)β3 (glycoprotein IIb- IIIa). A specific inhibitor of α(IIb)β3 blocked platelet aggregation induced by H2O2 and NaVO4, thus confirming that aggregation requires this receptor. In the presence of H2O2 and NaVO4, multiple platelet substrates were phosphorylated on tyrosine. Such tyrosine kinase response was necessary but not sufficient to activate α(IIb)β3, as detected by binding of soluble fibrinogen to platelets. Stirring of the platelets exposed to H2O2 and NaVO4 was also needed to allow for binding of fibrinogen to α(IIb)β3. The tyrosine kinase inhibitor genistein was able to block platelet aggregation induced by H2O2 and NaVO4, thus confirming that tyrosine kinase activity was needed to trigger α(IIb)β3 activation on stirring. N-Acetyl-L-cysteine, a cell-permeant antioxidant, blocked the tyrosine phosphorylation of platelet substrates and also the platelet aggregation induced by H2O2 and NaVO4. We found that β3 was phosphorylated on tyrosine in platelets exposed to H2O2 and NaVO4, even in the absence of aggregation. Hence, tyrosine phosphorylation of β3 might contribute to the 'priming' of α(IIb)β3 induced by H2O2 and NaVO4, whereby the receptor can become activated on stirring of the platelets.

Original languageEnglish (US)
Pages (from-to)1698-1706
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume18
Issue number11
DOIs
StatePublished - Jan 1 1998

Keywords

  • Glycoprotein IIb- IIIa
  • Platelets
  • Reactive oxygen species
  • Shear
  • Tyrosine kinases

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Priming of platelet α(IIb)β<sub>3</sub> by oxidants is associated with tyrosine phosphorylation of β<sub>3</sub>'. Together they form a unique fingerprint.

  • Cite this

    Irani, K., Pham, Y., Coleman, L. D., Roos, C., Cooke, G. E., Miodovnik, A., Karim, N., Wilhide, C. C., Bray, P. F., & Goldschmidt-Clermont, P. J. (1998). Priming of platelet α(IIb)β3 by oxidants is associated with tyrosine phosphorylation of β3. Arteriosclerosis, Thrombosis, and Vascular Biology, 18(11), 1698-1706. https://doi.org/10.1161/01.ATV.18.11.1698