Role of mitochondrial permeability transition pore in coated-platelet formation

Role of mitochondrial permeability transition pore in coated-platelet formation
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DOI:
10.1161/01.atv.0000152726.49229.bf
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发表时间:
2005-02-01
影响因子:
8.7
通讯作者:
Dale, GL
Dale, GL
中科院分区:
医学1区
文献类型:
--
作者:
Remenyi, G;Szasz, R;Dale, GL

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目的-包被血小板是在血小板与胶原和凝血酶共刺激过程中观察到的细胞亚群。包被血小板的重要特征包括在细胞表面保留多种α-颗粒蛋白和表达磷脂酰丝氨酸。线粒体通透性转换孔(MPTP)是细胞凋亡的关键步骤,并被认为参与了某些形式的血小板活化。本研究的目的是研究MPTP在合成的coated-platelets.Methods和Results -流式细胞术分析的coated-血小板生产被用来检查MPTP形成的药理效应的影响的作用。环孢菌素A、辅酶Q和邦克雷克酸都抑制MPTP的形成以及包被血小板的产生。氧化苯胂和二酰胺都是MPTP形成的增强剂,可刺激包被血小板的合成。另一种诱导剂MPTP形成,并不影响的百分比包覆血小板合成,但是,它确实增加了磷脂酰丝氨酸的水平暴露在表面上的coated-platelets.Conclusions -这些研究结果表明,MPTP的形成是一个不可分割的事件在合成的coated-platelets。虽然MPTP的确切功能仍有待确定,但这些数据支持越来越多的证据表明,血小板减少症相关事件是血小板活化过程的重要组成部分。
Objective - Coated-platelets are a subset of cells observed during costimulation of platelets with collagen and thrombin. Important characteristics of coated-platelets include retention of multiple alpha-granule proteins and expression of phosphatidylserine on the cell surface. The mitochondrial permeability transition pore ( MPTP) is a key step in apoptosis and is suggested to be involved in some forms of platelet activation. The objective of this study was to examine the role of MPTP in the synthesis of coated-platelets.Methods and Results - Flow cytometric analysis of coated-platelet production was used to examine the impact of pharmacological effectors of MPTP formation. Cyclosporin A, coenzyme Q, and bongkrekic acid all inhibit MPTP formation as well as production of coated-platelets. Phenylarsine oxide and diamide, both potentiators of MPTP formation, stimulate coated-platelet synthesis. Atractyloside, another inducer of MPTP formation, does not affect the percentage of coated-platelets synthesized; however, it does increase the level of phosphatidylserine exposed on the surface of coated-platelets.Conclusions - These findings indicate that MPTP formation is an integral event in the synthesis of coated-platelets. Although the exact function of the MPTP remains to be determined, these data support a growing body of evidence that apoptosis-associated events are vital components of the platelet activation process.