Thiosulfinates inhibit platelet aggregation and microparticle shedding at a calpain-dependent step

• Published in: Thrombosis and haemostasis Vol. 86; no. 5; p. 1284
• Main Authors: Rendu, F, Brohard-Bohn, B, Pain, S, Bachelot-Loza, C, Auger, J
• Format: Journal Article
• Language: English
• Published: Germany 01.11.2001
• Subjects: Allium - chemistry; Blood Platelets - drug effects; Blood Platelets - ultrastructure; Calpain - drug effects; Calpain - metabolism; Cell Membrane - drug effects; Clot Retraction; Enzyme Activation - drug effects; Humans; Membrane Microdomains - secretion; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Sulfinic Acids - pharmacology
• ISSN: 0340-6245
• DOI: 10.1055/s-0037-1616063

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 microM 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.