Abstract

Apoptosis has been shown to be associated with changes in cytosolic free calcium concentration ([Ca 2+] c). Here we show that the agonist thrombin induces activation of caspases 9 and 3 and translocation of the caspase active forms and procaspases to the cytoskeleton in human platelets. Dimethyl-BAPTA loading did not affect thrombin-induced caspase 9 and 3 activation or translocation suggesting that these responses are independent of increases in [Ca 2+] c. Treatment with thapsigargin plus ionomycin, to induce extensive Ca 2+ store depletion and subsequent increase in [Ca 2+] c, stimulates caspase activation although it was unable to induce caspase translocation to the cytoskeleton. Similar results were observed in cells loaded with dimethyl-BAPTA, suggesting that activation of caspases 9 and 3 by thapsigargin plus ionomycin does not require rises in [Ca 2+] c. These findings suggest that thrombin-induced caspase 9 and 3 activation and translocation are independent on rises in [Ca 2+] c but might require store depletion in human platelets.

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