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Calpain Activator Dibucaine Induces Platelet Apoptosis
School of Biological Science and Medical Engineering, Beijing University of Aeronautics and Astronautics, 37 Xueyuan Road, Haidian District, Beijing 100083, China
The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, 215007, China
* Author to whom correspondence should be addressed.
Received: 1 February 2011; in revised form: 6 March 2011 / Accepted: 18 March 2011 / Published: 25 March 2011
Abstract: Calcium-dependent calpains are a family of cysteine proteases that have been demonstrated to play key roles in both platelet glycoprotein Ibα shedding and platelet activation and altered calpain activity is associated with thrombotic thrombocytopenic purpura. Calpain activators induce apoptosis in several types of nucleated cells. However, it is not clear whether calpain activators induce platelet apoptosis. Here we show that the calpain activator dibucaine induced several platelet apoptotic events including depolarization of the mitochondrial inner transmembrane potential, up-regulation of Bax and Bak, down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation and phosphatidylserine exposure. Platelet apoptosis elicited by dibucaine was not affected by the broad spectrum metalloproteinase inhibitor GM6001. Furthermore, dibucaine did not induce platelet activation as detected by P-selectin expression and PAC-1 binding. However, platelet aggregation induced by ristocetin or α-thrombin, platelet adhesion and spreading on von Willebrand factor were significantly inhibited in platelets treated with dibucaine. Taken together, these data indicate that dibucaine induces platelet apoptosis and platelet dysfunction.
Keywords: platelets; calpain; dibucaine; platelet apoptosis; platelet activation
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Zhang, W.; Liu, J.; Sun, R.; Zhao, L.; Du, J.; Ruan, C.; Dai, K. Calpain Activator Dibucaine Induces Platelet Apoptosis. Int. J. Mol. Sci. 2011, 12, 2125-2137.
Zhang W, Liu J, Sun R, Zhao L, Du J, Ruan C, Dai K. Calpain Activator Dibucaine Induces Platelet Apoptosis. International Journal of Molecular Sciences. 2011; 12(4):2125-2137.
Zhang, Weilin; Liu, Jun; Sun, Ruichen; Zhao, Lili; Du, Juan; Ruan, Changgeng; Dai, Kesheng. 2011. "Calpain Activator Dibucaine Induces Platelet Apoptosis." Int. J. Mol. Sci. 12, no. 4: 2125-2137.