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 Goldschmidt-Clermont

Research output: Contribution to journalArticle

37 Citations (Scopus)

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
Pages (from-to)1698-1706
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume18
Issue number11
StatePublished - Nov 25 1998
Externally publishedYes

Fingerprint

Platelet Aggregation Inhibitors
Oxidants
Platelet Aggregation
Blood Platelets
Phosphorylation
Tyrosine
Protein-Tyrosine Kinases
Fibrinogen
Receptor Aggregation
Vanadates
Genistein
Vascular System Injuries
Acetylcysteine
3-tyrosine
Phosphoric Monoester Hydrolases
Integrins
Reactive Oxygen Species
Glycoproteins
Thrombosis
Antioxidants

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Irani, K., Pham, Y., Coleman, L. D., Roos, C., Cooke, G. E., Miodovnik, A., ... Goldschmidt-Clermont, P. (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.

Priming of platelet α(IIb)β3 by oxidants is associated with tyrosine phosphorylation of β3. / Irani, Kaikobad; Pham, Youm; Coleman, Lindsay D.; Roos, Christine; Cooke, Glen E.; Miodovnik, Amir; Karim, Nayeem; Wilhide, Calvin C.; Bray, Paul F.; Goldschmidt-Clermont, Pascal.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 18, No. 11, 25.11.1998, p. 1698-1706.

Research output: Contribution to journalArticle

Irani, K, Pham, Y, Coleman, LD, Roos, C, Cooke, GE, Miodovnik, A, Karim, N, Wilhide, CC, Bray, PF & Goldschmidt-Clermont, P 1998, 'Priming of platelet α(IIb)β3 by oxidants is associated with tyrosine phosphorylation of β3', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 18, no. 11, pp. 1698-1706.
Irani K, Pham Y, Coleman LD, Roos C, Cooke GE, Miodovnik A et al. Priming of platelet α(IIb)β3 by oxidants is associated with tyrosine phosphorylation of β3. Arteriosclerosis, Thrombosis, and Vascular Biology. 1998 Nov 25;18(11):1698-1706.
Irani, Kaikobad ; Pham, Youm ; Coleman, Lindsay D. ; Roos, Christine ; Cooke, Glen E. ; Miodovnik, Amir ; Karim, Nayeem ; Wilhide, Calvin C. ; Bray, Paul F. ; Goldschmidt-Clermont, Pascal. / Priming of platelet α(IIb)β3 by oxidants is associated with tyrosine phosphorylation of β3. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 1998 ; Vol. 18, No. 11. pp. 1698-1706.
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AU - Miodovnik, Amir

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