Quantitative proteomics analysis of platelet-derived microparticles reveals distinct protein signatures when stimulated by different physiological agonists
Quantitative proteomics analysis of platelet-derived microparticles reveals distinct protein signatures when stimulated by different physiological agonists
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DOI：
10.1016/j.jprot.2015.03.013
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发表时间：
2015-05-21
影响因子：
3.3
通讯作者：
Larsen, Martin R.
中科院分区：
文献类型：
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作者：
Milioli, Marco;Ibanez-Vea, Maria;Larsen, Martin R.
血小板衍生的微泡(PMPs)是一类在活化和凋亡过程中从血小板中释放出来的异质性微泡。不同的血小板激活可能会影响PMP蛋白的谱和在细胞间通讯中的作用。在这里，我们进行了一项定量蛋白质组学研究，以表征由四个不同激活的血小板样本产生的PMPs的蛋白质含量。我们选择了已知的激活血小板的生理激动剂，如ADP、凝血酶和胶原。以凝血酶为对照，凝血酶主要用于体外产生PMPs。血小板的激活遵循已知的激动剂强度等级，其中ADP是最弱的激活，凝血酶和胶原的刺激是最强的。我们的蛋白质组学分析使3383个蛋白质得以定量，其中428个膜蛋白和131个可溶性蛋白质在至少一个分析条件下被发现显著不同。较强激动剂的激活导致PMPs中与血小板激活相关的蛋白质的丰富。此外，当使用更强的激活时，参与血小板脱颗粒的蛋白质和来自电子传输链的蛋白质在PMPs中不那么丰富。总的来说，我们的数据描述了血小板生理性激活后PMPs最详细的特征。此外，我们发现PMP蛋白的含量高度依赖于参与血小板刺激的生理激动剂的类型。生物学意义血小板衍生的MPS(PMPs)是一群在各种刺激下由血小板激活而产生的囊泡，已知参与了几个生理和病理过程。这篇手稿使用基于质谱学的定量蛋白质组学研究了通过执行四种不同的激活程序获得的PMPs的蛋白质图谱。通过跟踪已知的生理激动剂强度等级，我们的发现表明激动剂强度与与血小板介导的过程有关的蛋白质之间存在生物联系，如激活和脱颗粒。这些数据可能为理解PMP的生物学作用和形成提供新的见解。(C)由爱思唯尔出版的2015年。
Platelet-derived MPs (PMPs) are a heterogeneous population of microvesicles released from platelets upon activation and apoptosis. Different platelet activations may affect PMP protein profiles and roles in intercellular communication. Here, we performed a quantitative proteomics study to characterize the protein content of PMPs generated by four differentially activated platelet samples. We selected known physiological agonists for platelet activation such as ADP, thrombin and collagen. Thrombin, which is mostly used to generate PMPs in vitro, was set as control. Platelets were activated by following a known agonist strength scale in which ADP was the weakest activation and thrombin and collagen stimulations were the strongest ones. Our proteomic analysis allowed the quantification of 3383 proteins, of which 428 membrane and 131 soluble proteins were found as significantly different in at least one of the analyzed conditions. Activation with stronger agonists led to the enrichment of proteins related to platelet activation in PMPs. In addition, proteins involved in platelet degranulation and proteins from the electron transport chain were less abundant in PMPs when stronger activation was used. Collectively, our data describe the most detailed characterization of PMPs after platelet physiological activation. Furthermore, we show that PMP protein content is highly dependent on the type of physiological agonist involved in platelet stimulation.Biological significancePlatelet-derived MPs (PMPs) are a population of vesicles generated upon platelet activation by various stimuli known to be involved in several physiological and pathological processes. This manuscript investigates the protein profile of PMPs obtained by performing four different activation protocols using mass spectrometry-based quantitative proteomics. By following a known physiological agonist strength scale our findings suggest a biological link between agonist strength and proteins associated to platelet mediated processes such as activation and degranulation. These data may provide new insights for understanding PMP biological role and formation. (C) 2015 Published by Elsevier B.V.