Caspase inhibition decreases both platelet phosphatidylserine exposure and aggregation: caspase inhibition of platelets

Thrombosis Research
Zoë CohenPaul McDonagh

Abstract

Apoptosis of nucleated cells is regulated by caspases, a group of cysteine proteases, and is characterized by phosphatidylserine expression on the outer leaflet of the plasma membrane. Reports indicate that platelets contain caspases. However, the role of caspases in platelet function is not well understood. When platelets become activated, they express phosphatidylserine (PS) on the outer leaflet of the plasma membrane. In addition, platelets aggregate when activated. The aims of this study were to determine if caspase inhibition (using the pan-caspase inhibitor zVAD-fmk): (1) decreased PS expression and (2) decreased platelet aggregation following activation. Flow cytometry was used to determine PS expression and a platelet aggregometer was used to assess aggregation. We found that platelets treated with zVAD-fmk significantly decreased both A23187-induced PS exposure (total fluorescence index, TFI: A23187=791.42+/-174; zVAD+A23187=92.97+/-57, p<==0.05) and ADP-induced PS exposure (TFI: ADP=669.24+/-145, zVAD+ADP=174.6+/-151, p<==0.05). Further, treatment with zVAD-fmk significantly decreased ADP-induced platelet aggregation (%: untreated=80+/-1.5, zVAD treated=69+/-3.0, p<==0.05). These results indicate that caspases play a ...Continue Reading

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Citations

Aug 19, 2014·Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis·Yunlong ZhuangChuanfu Zhu
Aug 5, 2005·Oncogene·Sophie LaunayCarmen Garrido
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Jul 18, 2017·Journal of Acupuncture and Meridian Studies·Azadeh Meshkini, Masoumeh Tahmasbi

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