Neuroproteome changes after ischemia/reperfusion injury and tissue plasminogen activator administration in rats: a quantitative iTRAQ proteomics study.
Neuroproteome changes after ischemia/reperfusion injury and tissue plasminogen activator administration in rats: a quantitative iTRAQ proteomics study.
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DOI：
10.1371/journal.pone.0098706
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kassner A
中科院分区：
文献类型：
--
作者：
Merali Z;Gao MM;Bowes T;Chen J;Evans K;Kassner A
溶栓、重组组织型纤溶酶原激活剂（rt-PA）是唯一获批的急性缺血性卒中（AIS）治疗药物。在AIS后给药时，rt-PA具有许多不良多效性作用，目前对其了解甚少。rt-PA给药后显示差异表达的蛋白质的鉴定可以提供对这些多效性作用的了解。在本研究中，我们使用2D-LC MS/MS iTRAQ蛋白质组学分析、蛋白质印迹和途径分析来分析36只接受假手术或短暂性大脑中动脉闭塞手术的大鼠皮质脑组织中rt-PA给药后24小时蛋白质表达的变化。rt-PA给药后，我们报告了18种蛋白质表达的改变，其中许多蛋白质参与兴奋性神经递质功能或细胞骨架结构。Western blot检测GAD 2和EAAT 1的表达变化。用IPA途径分析工具分析了所鉴定的蛋白质之间的相互作用，发现三种蛋白质：DPYSL 2、RTN 4和NF-kB复合物具有作为网络中的关键蛋白质的特征。这些差异蛋白表达可能反映了rt-PA在脑卒中后的多效性，并为进一步研究rt-PA的毒副作用机制提供了线索。这可能在溶栓治疗AIS的临床环境中具有重要意义。
The thrombolytic, recombinant tissue plasminogen activator (rt-PA) is the only approved therapy for acute ischemic stroke (AIS). When administered after AIS, rt-PA has many adverse pleiotropic actions, which are currently poorly understood. The identification of proteins showing differential expression after rt-PA administration may provide insight into these pleiotropic actions. In this study we used a 2D-LC MS/MS iTRAQ proteomic analysis, western blotting, and pathway analysis to analyze changes in protein expression 24-hours after rt-PA administration in the cortical brain tissue of 36 rats that underwent a sham or transient middle cerebral artery occlusion surgery. After rt-PA administration we reported alterations in the expressions of 18 proteins, many of which were involved in excitatory neurotransmitter function or cytoskeletal structure. The expression changes of GAD2 and EAAT1 were validated with western blot. The interactions between the identified proteins were analyzed with the IPA pathway analysis tool and three proteins: DPYSL2, RTN4, and the NF-kB complex, were found to have characteristics of being key proteins in the network. The differential protein expressions we observed may reflect pleiotropic actions of rt-PA after experimental stroke, and shine light on the mechanisms of rt-PA's adverse effects. This may have important implications in clinical settings where thrombolytic therapy is used to treat AIS.
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