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Thiosulfinates Inhibit Platelet Aggregation and Microparticle Shedding at a Calpain-dependent Step

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Issue: 2001: 86/5 (Nov) pp.1136-1342
Pages: 1284-1291

Thiosulfinates Inhibit Platelet Aggregation and Microparticle Shedding at a Calpain-dependent Step

Francine Rendu(1), Brigitte Brohard-Bohn(1), Sabine Pain(1), Christilla Bachelot-Loza(1), Jacques Auger(2)
(1)U 428 INSERM, Faculté de Pharmacie, Université René Descartes Paris V, Paris, (2)IRBI, Université François Rabelais, Tours, France

Summary

Thiosulfinates (TSs) are sulfur compounds generated through the processing of different Allium species with antiplatelet property. To further define this platelet inhibitory effect we studied diallyl-TS (Al2TS), dipropyl-TS (Pr2TS), and dimethyl-TS (Me2TS) on platelet responses. The three TSs inhibited dose-dependent platelet aggregation, with IC50 values of 15 ± 2, 19 ± 2, and 9 ± 1 µM for Al2TS, Pr2TS and Me2TS, respectively. TSs had no effect on the expression of a platelet procoagulant surface, measured by flow cytometry as the binding of annexin V-FITC. They inhibited the microparticle shedding and clot retraction. Since the microparticle shedding is a calpain-activation dependent step, we assessed calpain activation by analysis of autoproteolysis in shorter active forms and by talin proteolysis in the presence of TSs. Calpain activation was inhibited by TSs independently of fibrinogen binding. Thus, TSs represent a new category of platelet inhibitors, acting on calpain- induced events.