Vitamin D-Binding Protein Acts in the Actin Scavenge System and Can Have Increased Expression During Aspirin Therapy
Vitamin D-Binding Protein Acts in the Actin Scavenge System and Can Have Increased Expression During Aspirin Therapy
复制标题
维生素 D 结合蛋白在肌动蛋白清除系统中发挥作用，并在阿司匹林治疗期间表达增加
DOI：
10.2174/1567202613666160506125622
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发表时间：
2016-01-01
影响因子：
2.1
通讯作者：
Liu, Shilian
中科院分区：
文献类型：
--
作者：
Li, Ziquan;Gao, Jifang;Liu, Shilian
虽然阿司匹林预防脑血栓的临床疗效已得到证实，但其作用机制仍存在争议。为了更好地理解这些机制并识别潜在的生物标志物，利用二维凝胶电泳（2-DE）结合基质辅助激光解吸电离飞行时间质谱法对18名脑血栓发病时阿司匹林治疗前（对照组）和阿司匹林治疗后（实验组）的患者进行了比较蛋白质组分析。 (MALDIT-OF/MS)。在 228 个 2-DE 鉴定的差异表达蛋白点中，11 个蛋白显示出超过 1.5 倍的差异。其中，通过蛋白质印迹进一步检查维生素 D 结合蛋白 (DBP) 和肌动蛋白，并显示出一致的结果，相对于治疗前 (66.33 +/- 5.61)，阿司匹林治疗后 DBP 水平显着增加 (114.04 +/- 16.69)，而肌动蛋白则显示出相反的趋势（两次比较 p < 0.01）。接下来，DBP 和肌动蛋白的免疫共沉淀分析显示直接结合。此外，使用 Ingenuity Pathway Analysis 软件构建了 DBP 和其他差异表达蛋白的蛋白质-蛋白质相互作用网络。这些结果表明 DBP 在肌动蛋白清除系统中起作用，因此 DBP 水平的升高与脑血栓患者的阿司匹林治疗相关。这些发现还表明，阿司匹林可能通过 DBP 和其他 DBP 相关蛋白的作用来预防血小板聚集和血栓形成。
While the clinical efficacy of aspirin in cerebral thrombosis prevention has been well established, its mechanism of action is still controversial. In an effort to better understand these mechanisms and to identify potential biomarkers, comparative proteomic analysis between 18 patients both pre-aspirin treatment at the time of cerebral thrombotic onset (control group) and post-aspirin treatment (experiment group) was carried out using two-dimensional gel electrophoresis (2-DE) in combination with matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDIT-OF/MS). Of the 228 2-DE identified differentially expressed protein spots, 11 proteins showed more than a 1.5-fold difference. Of these, vitamin D-binding protein (DBP) and actin were further examined via Western blot and showed consistent results, with DBP levels significantly increased post-aspirin treatment (114.04 +/- 16.69) relative to pre-treatment (66.33 +/- 5.61) while actin showed the opposite trend (p < 0.01 for both comparisons). Next, co-immunoprecipitation analysis of DBP and actin showed direct binding. Furthermore, a protein-protein interaction network of DBP and the other differentially expressed proteins was constructed using Ingenuity Pathway Analysis software. These results suggest that DBP acts in the actin scavenge system and consequently the increase in DBP levels correlated with aspirin therapy in cerebral thrombotic patients. These findings also suggest that aspirin may prevent platelet aggregation and thrombosis through the actions of DBP and other DBP related proteins.