Platelets Proteomic Profiles of Acute Ischemic Stroke Patients.
Platelets Proteomic Profiles of Acute Ischemic Stroke Patients.
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DOI：
10.1371/journal.pone.0158287
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Sener A
中科院分区：
文献类型：
--
作者：
Cevik O;Baykal AT;Sener A
血小板在卒中的发病机制中起着至关重要的作用，抗血小板药物的存在可用于其治疗和预防。通过使用基于LC-MS的蛋白质表达谱，分析了来自中风患者的血小板，然后将其与该疾病背景下的蛋白质组学分析结果相关联。本研究基于缺血性卒中后入院并在发病后24小时内抽取静脉血的患者。在UPLC-ESI-qTOF-MS/MS系统上一式三份进行血小板胰蛋白酶消化物的无标记蛋白表达分析，并使用ProteinLynx Global Server（v2.5，沃茨）进行串联质谱数据提取。根据审查的智人数据库（www.uniprot.org）检索肽序列，并通过Progenesis LC-MS软件（V4.0，非线性动力学）实现蛋白质变异的定量。这些血小板的无标记差异蛋白质组学分析确保了500种蛋白质被鉴定，并且发现这些蛋白质中的83种具有统计学显著性。差异表达的蛋白质参与各种过程，如炎症反应、细胞运动、免疫细胞运输、细胞间信号传导和相互作用、血液系统发育和功能以及核酸代谢。髓过氧化物酶、花生四烯酸12-脂氧合酶和富含组氨酸的糖蛋白的表达参与细胞代谢过程，crk样蛋白和ras同源基因家族成员A参与细胞信号传导，玻连蛋白、血小板反应蛋白1、整合素α 2b和整合素β 3参与细胞粘附。载脂蛋白H、免疫球蛋白重链恒定区γ 1和免疫球蛋白重链恒定区γ 3参与结构，载脂蛋白A-I和α-1-微球蛋白/bikunin前体参与转运，补体成分3和簇蛋白参与免疫蛋白，如已经讨论的。我们的数据提供了一个深入了解的蛋白质参与血小板的活化反应在缺血性中风。可以说，这项研究奠定了未来的机制研究的基础。
Platelets play a crucial role in the pathogenesis of stroke and antiplatelet agents exist for its treatment and prevention. Through the use of LC-MS based protein expression profiling, platelets from stroke patients were analyzed and then correlated with the proteomic analyses results in the context of this disease. This study was based on patients who post ischemic stroke were admitted to hospital and had venous blood drawn within 24 hrs of the incidence. Label-free protein expression analyses of the platelets’ tryptic digest was performed in triplicate on a UPLC-ESI-qTOF-MS/MS system and ProteinLynx Global Server (v2.5, Waters) was used for tandem mass data extraction. The peptide sequences were searched against the reviewed homo sapiens database (www.uniprot.org) and the quantitation of protein variation was achieved through Progenesis LC-MS software (V4.0, Nonlinear Dynamics). These Label-free differential proteomics analysis of platelets ensured that 500 proteins were identified and 83 of these proteins were found to be statistically significant. The differentially expressed proteins are involved in various processes such as inflammatory response, cellular movement, immune cell trafficking, cell-to-cell signaling and interaction, hematological system development and function and nucleic acid metabolism. The expressions of myeloperoxidase, arachidonate 12-Lipoxygenase and histidine-rich glycoprotein are involved in cellular metabolic processes, crk-like protein and ras homolog gene family member A involved in cell signaling with vitronectin, thrombospondin 1, Integrin alpha 2b, and integrin beta 3 involved in cell adhesion. Apolipoprotein H, immunoglobulin heavy constant gamma 1 and immunoglobulin heavy constant gamma 3 are involved in structural, apolipoprotein A-I, and alpha-1-microglobulin/bikunin precursor is involved in transport, complement component 3 and clusterin is involved in immunity proteins as has been discussed. Our data provides an insight into the proteins that are involved in the platelets’ activation response during ischemic stroke. It could be argued that this study lays the foundation for future mechanistic studies.