H2O2 activity on platelet adhesion to fibrinogen and protein tyrosine phosphorylation

Platelets represent a target of reactive oxygen species produced under oxid ative stress conditions. Controversial data on the effect of these species on platelet functions have been reported so far. In this study we evaluated the effect of a wide range of H2O2 concentrations on platelet adhesion to immobilized fibrinogen and on pp72(syk) and pp125(FAK) tyrosine phosphoryla tion. Our results demonstrate that: (1) H2O2 does not affect the adhesion o f unstimulated or apyrase-treated platelets to immobilized fibrinogen; (2) H2O2 does not affect pp72(syk) phosphorylation induced by platelet adhesion to fibrinogen-coated dishes; (3) H2O2 reduces, in a dose-dependent fashion , pp125(FAK) phosphorylation of fibrinogen-adherent platelets; (4) concentr ations of H2O2 near to physiological values (10-12 mu M) are able to streng then the subthreshold activation of pp125(FAK) induced by epinephrine in ap yrase-treated platelets; (5) H2O2 doses higher than 0.1 mM inhibit ADP-indu ced platelet aggregation and dense granule secretion. The ability of H2O2 t o modulate pp125(FAK) phosphorylation suggests a role of this molecule in p hysiological hemostasis as well as in thrombus generation. (C) 2000 Elsevie r Science B.V. All rights reserved.