Hydrogen Peroxide Generation Induces pp60src Activation in Human Platelets

Reactive oxygen species, such as H2O2, have been recognized as intracellular messengers involved in several cell functions. Here we report the activation of the tyrosine kinase pp60src by H2O2, a mechanism required for the activation of store-mediated Ca2+ entry (SMCE) in human platelets. Treatment of platelets with H2O2 resulted in a time- and concentration-dependent activation of pp60src. Incubation with GF 109203X, a protein kinase C (PKC) inhibitor, prevented H2O2-induced pp60src activation. In contrast, dimethyl-BAPTA loading did not affect this response, suggesting that activation of pp60src by H2O2 is independent of increases in [Ca2+]i. Cytochalasin D, an inhibitor of actin polymerization, significantly reduced H2O2-induced pp60src activation. We found that platelet stimulation with thapsigargin (TG) plus ionomycin (Iono) or thrombin induced rapid H2O2 production, a mechanism independent of elevations in [Ca2+]i. Treatment of platelets with catalase attenuated TG plus Iono- and thrombin-induced activation of pp60src. In addition, catalase as well as the pp60src inhibitor, PP1, reduced both the activation of SMCE and the coupling between the hTrp1 and the IP3R type II without having any effect on the maintenance of SMCE. Consistent with the role of PKC in the activation of pp60src by H2O2, the PKC inhibitors GF 109202X and Ro-31-8220 were found to reduced SMCE in platelets. This study suggests that platelet activation with TG plus Iono or thrombin is associated with H2O2 production, which acts as a second messenger by stimulating pp60src by a PKC-dependent pathway and is involved in the activation of SMCE in these cells.

• Publication year

  2004

• Venue

  Journal of Biological Chemistry

• Publication date

  2004-01-16

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1074/jbc.M307963200PMID 14581479
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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