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- Title
Involvement of Rac in thromboxane A<sub>2</sub>-induced human platelet activation: Regulation of sCD40 ligand release and PDGF-AB secretion.
- Authors
YASUNARI KAGEYAMA; TOMOAKI DOI; RIE MATSUSHIMA-NISHIWAKI; YUKO IIDA; SHIGERU AKAMATSU; AKIRA KONDO; GEN KUROYANAGI; NAOHIRO YAMAMOTO; JUN MIZUTANI; TAKANOBU OTSUKA; HARUHIKO TOKUDA; HIROKI IIDA; OSAMU KOZAWA; SHINJI OGURA
- Abstract
We have previously shown that glycoprotein Ib/IX/V activation stimulates the release of the soluble CD40 ligand (sCD40L) via the generation of thromboxane A2 from human platelets. In the present study, the role of Rac, which is a member of the Rho family, was investigated in the thromboxane A2-stimulated release of platelet-derived growth factor (PDGF)-AB and sCD40L in human platelets. U46619, a thromboxane receptor agonist, stimulated the activation of Rac time-dependently in human platelets, and NSC23766, a selective inhibitor of the Rac-guanine nucleotide exchange factor interaction, reduced the U46619-induced platelet aggregation. NSC23766 markedly suppressed the U46619-induced p38 mitogen-activated protein (MAP) kinase phosphorylation. The thromboxane A2-induced release of PDGF-AB and sCD40L was significantly suppressed by NSC23766 in a dose-dependent manner. In addition, NSC23766 reduced the sCD40L release stimulated by ristocetin, a glycoprotein Ib/IX/V activator. These results indicate that Rac regulates the thromboxane A2-induced stimulation of PDGF-AB secretion and sCD40L release via the p38 MAP kinase in human platelets.
- Subjects
GLYCOPROTEINS; THROMBOXANES; CD40 antigen; LIGANDS (Biochemistry); PLATELET-derived growth factor; GUANINE nucleotide exchange factors; MITOGEN-activated protein kinases
- Publication
Molecular Medicine Reports, 2014, Vol 10, Issue 1, p107
- ISSN
1791-2997
- Publication type
Article
- DOI
10.3892/mmr.2014.2143