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

Francine Rendu; Brigitte Brohard-Bohn; Sabine Pain; Christilla Bachelot-Loza; Jacques Auger

doi:10.1055/s-0037-1616063

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2001; 86(05): 1284-1291
DOI: 10.1055/s-0037-1616063

Review Article

Schattauer GmbH

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

Authors

Francine Rendu

¹U 428 INSERM, Faculté de Pharmacie, Université René Descartes Paris V, Paris
Brigitte Brohard-Bohn

¹U 428 INSERM, Faculté de Pharmacie, Université René Descartes Paris V, Paris
Sabine Pain

¹U 428 INSERM, Faculté de Pharmacie, Université René Descartes Paris V, Paris
Christilla Bachelot-Loza

¹U 428 INSERM, Faculté de Pharmacie, Université René Descartes Paris V, Paris
Jacques Auger

²IRBI, Université François Rabelais, Tours, France

Abstract

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 cal-pain-induced events.

Keywords

Allium - calpain - microparticles - platelet aggregation - talin

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Referenzen

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