کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6001664 | 1182955 | 2014 | 7 صفحه PDF | دانلود رایگان |
BackgroundDepolarization of mitochondrial inner transmembrane potential (ÎΨm) is a key biochemical manifestation of the intrinsic apoptosis pathway in anucleate platelets. Little is known, however, about the relationship between ÎΨm depolarization and downstream morphological manifestations of platelet apoptosis, cell shrinkage and microparticle (MP) formation.ObjectivesTo elucidate this relationship in human platelets.Materials and MethodsUsing flow cytometry, we analyzed ÎΨm depolarization, platelet shrinkage and MP formation in platelets treated with BH3-mimetic ABT-737 and calcium ionophore A23187, well-known inducers of intrinsic platelet apoptosis.ResultsWe found that at optimal treatment conditions (90 min, 37 °C) both ABT-737 and A23187 induce ÎΨm depolarization in the majority (88-94%) of platelets and strongly increase intracellular free calcium. In contrast, effects of A23187 and ABT-737 on platelet shrinkage and MP formation are quite different. A23187 strongly stimulates cell shrinkage and MP formation, whereas ABT-737 only weakly induces these events (10-20% of the effect seen with A23187, P < 0.0001).ConclusionsThese data indicate that a high level of ÎΨm depolarization and intracellular free calcium does not obligatorily ensure strong platelet shrinkage and MP formation. Since ABT-737 efficiently induces clearance of platelets from the circulation, our results suggest that platelet clearance may occur in the absence of the morphological manifestations of apoptosis.
Journal: Thrombosis Research - Volume 133, Issue 1, January 2014, Pages 73-79