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PubMed · 16961585

Thrombin-triggered platelet apoptosis.

V Leytin·D J Allen·S Mykhaylov·E Lyubimov·J Freedman
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Abstract

BACKGROUND: Thrombin is primarily known as a coagulation factor and as an inducer of platelet activation and aggregation. It has been reported that thrombin modulates apoptosis of nucleated cells. OBJECTIVES: The current study investigated whether thrombin can affect apoptosis in anucleated human platelets. METHODS: Using flow cytometry, we studied platelet apoptosis at the single-cell level, analyzing markers of mitochondrial and cytoplasmic apoptosis. Western blotting was also employed, in addition to flow cytometry, for determining the expression of Bcl-2 family proteins. RESULTS: We found that human alpha-thrombin induced four key manifestations of apoptosis in human platelets: (i) mitochondrial inner transmembrane potential (DeltaPsi m) depolarization; (ii) strong expression of pro-apoptotic Bax and Bak proteins but only weak expression of anti-apoptotic Bcl-2 protein; (iii) caspase-3 activation; and (iv) phosphatidylserine (PS) exposure. CONCLUSIONS: This study demonstrates that, aside from its 'classical' function as an inducer of platelet activation, thrombin can trigger platelet apoptosis, where it acts as a death ligand. These data indicate that thrombin triggers platelet apoptosis by impacting on several intracellular apoptotic targets, including shifting the balance between Bcl-2 regulatory proteins in a pro-apoptotic direction, depolarizing the inner mitochondrial membrane, activating the executioner caspase-3, and stimulating aberrant exposure of PS on the platelet surface.

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ApoptosisBlood PlateletsCaspase 3Cell MembraneCoagulantsEnzyme ActivationHumansIn Vitro TechniquesMembrane GlycoproteinsMembrane Potential, MitochondrialMembrane ProteinsMitochondriaPhosphatidylserinesPlatelet AggregationPlatelet Glycoprotein GPIIb-IIIa ComplexPlatelet Glycoprotein GPIb-IX ComplexProto-Oncogene Proteins c-bcl-2Thrombinbcl-2 Homologous Antagonist-Killer Proteinbcl-2-Associated X ProteinJournal ArticleResearch Support, Non-U.S. Gov't

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V Leytin, D J Allen, S Mykhaylov, E Lyubimov, J Freedman. 2006-09-08. Thrombin-triggered platelet apoptosis.. https://doi.org/10.1111/j.1538-7836.2006.02200.x

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