BH3 mimetics modulate calcium homeostasis in platelets

摘要

In line with the findings of Schoenwaelder and Jackson, we agree that the BH3 mimetics ABT-263 and ABT-737 inhibit normal platelet function. However, while Schoenwaelder et al attribute the inhibition of platelet activation on ABT-263 treatment to receptor ectodomain shedding, we believe that a modulation of cellular calcium flux contributes to the thrombocytopathy. Our hypothesis that ABT-263 may modify cellular calcium homeostasis was based on 2 observations. Firstly, exposure of platelets to ABT-263 resulted in an immediate increase in free cytosolic calcium and secondly, exposure of platelets to ABT-263 for 2 hours resulted in a depletion of intracellular calcium stores.