Abou-Abbass Hussein, Bahmad Hisham, Abou-El-Hassan Hadi, Zhu Rui, Zhou Shiyue, Dong Xue, Hamade Eva, Mallah Khalil, Zebian Abir, Ramadan Naify, Mondello Stefania, Fares Jawad, Comair Youssef, Atweh Samir, Darwish Hala, Zibara Kazem, Mechref Yehia, Kobeissy Firas
Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Faculty of Medicine, Beirut Arab University, Beirut, Lebanon.
Electrophoresis. 2016 Jun;37(11):1562-76. doi: 10.1002/elps.201500583. Epub 2016 Mar 29.
As populations age, the number of patients sustaining traumatic brain injury (TBI) and concomitantly receiving preinjury antiplatelet therapy such as aspirin (ASA) and clopidogrel (CLOP) is rising. These drugs have been linked with unfavorable clinical outcomes following TBI, where the exact mechanism(s) involved are still unknown. In this novel work, we aimed to identify and compare the altered proteome profile imposed by ASA and CLOP when administered alone or in combination, prior to experimental TBI. Furthermore, we assessed differential glycosylation PTM patterns following experimental controlled cortical impact model of TBI, ASA, CLOP, and ASA + CLOP. Ipsilateral cortical brain tissues were harvested 48 h postinjury and were analyzed using an advanced neuroproteomics LC-MS/MS platform to assess proteomic and glycoproteins alterations. Of interest, differential proteins pertaining to each group (22 in TBI, 41 in TBI + ASA, 44 in TBI + CLOP, and 34 in TBI + ASA + CLOP) were revealed. Advanced bioinformatics/systems biology and clustering analyses were performed to evaluate biological networks and protein interaction maps illustrating molecular pathways involved in the experimental conditions. Results have indicated that proteins involved in neuroprotective cellular pathways were upregulated in the ASA and CLOP groups when given separately. However, ASA + CLOP administration revealed enrichment in biological pathways relevant to inflammation and proinjury mechanisms. Moreover, results showed differential upregulation of glycoproteins levels in the sialylated N-glycans PTMs that can be implicated in pathological changes. Omics data obtained have provided molecular insights of the underlying mechanisms that can be translated into clinical bedside settings.
随着人口老龄化，遭受创伤性脑损伤（TBI）并同时接受伤前抗血小板治疗（如阿司匹林（ASA）和氯吡格雷（CLOP））的患者数量正在增加。这些药物与TBI后的不良临床结局有关，但其确切机制仍不清楚。在这项新的研究中，我们旨在识别和比较在实验性TBI之前单独或联合使用ASA和CLOP时所导致的蛋白质组变化。此外，我们评估了在实验性TBI、ASA、CLOP和ASA + CLOP的控制性皮质撞击模型后的差异糖基化PTM模式。在损伤后48小时收集同侧皮质脑组织，并使用先进的神经蛋白质组学LC-MS/MS平台进行分析，以评估蛋白质组和糖蛋白的变化。有趣的是，揭示了与每组相关的差异蛋白（TBI组22个，TBI + ASA组41个，TBI + CLOP组44个，TBI + ASA + CLOP组34个）。进行了先进的生物信息学/系统生物学和聚类分析，以评估生物网络和蛋白质相互作用图谱，阐明实验条件下涉及的分子途径。结果表明，单独给予时，参与神经保护细胞途径的蛋白质在ASA和CLOP组中上调。然而，给予ASA + CLOP显示与炎症和促损伤机制相关的生物途径富集。此外，结果显示唾液酸化N-聚糖PTM中糖蛋白水平的差异上调，这可能与病理变化有关。获得的组学数据提供了潜在机制的分子见解，可转化为临床床边应用。
