Biomarker and Drug Target Discovery Using Quantitative Proteomics Post-Intracerebral Hemorrhage Stroke in the Rat Brain.
Biomarker and Drug Target Discovery Using Quantitative Proteomics Post-Intracerebral Hemorrhage Stroke in the Rat Brain.
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在大鼠大脑中脑出血后，生物标志物和药物靶标的发现使用定量蛋白质组学。
DOI：
10.1007/s12031-018-1206-z
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Gong Y
中科院分区：
文献类型：
--
作者：
Deng S;Feng S;Wang W;Zhao F;Gong Y
急性脑出血（ICH）的病理机制仍不清楚，尚未得到证实。在本研究中，我们使用定量蛋白质组学来阐明病理机制，并通过组织蛋白质组学在大鼠急性ICH模型中鉴定新的生物标志物和治疗靶点候选者。采用脑出血（n = 6）和假手术（n = 6）诱导大鼠脑出血，24 h后取脑组织。使用基于TMT-LC-MS/MS的蛋白质组学方法来定量脑组织中的差异蛋白质组，并通过独创性途径分析进一步分析结果，以探索上传数据中涉及的典型途径和关系。通过定量分析，我们发现在ICH 24 h组中鉴定的96种分泌蛋白与对照组相比有显著差异（P < 0.05）;在这些蛋白中，57种蛋白的丰度增加，39种蛋白的丰度减少。差异表达蛋白的生物信息学分析表明，蛋白定位和ERK 1和ERK 2级联是差异蛋白浓度最高的两个生物学过程。具有高蛋白质置信水平的顶级蛋白质-蛋白质作用网络是白蛋白和ERK信号通路。通过蛋白质印迹分析评估脑组织中的白蛋白、ERK和p-ERK，在ICH组中观察到白蛋白和p-ERK的表达水平较高。我们的蛋白质组学结果突出了ERK 1和ERK 2级联的生物学过程中的重要变化，这可能是未来ICH干预的目标。据我们所知，这项研究提供了脑组织中ICH的深入分析，我们提出了96个新的ICH生物标志物候选者，包括白蛋白和ERK。本文的在线版本（10.1007/s12031-018-1206-z）包含补充材料，可供授权用户使用。
The pathological mechanisms of acute intracerebral hemorrhage (ICH) remain unknown and unverified. In the present study, we used quantitative proteomics to elucidate the pathological mechanisms and to identify novel biomarker and therapeutic target candidates via tissue proteome in a rat model of acute ICH. Rats were experimentally induced with ICH (n = 6) or Sham (n = 6), and their brain tissue was obtained by 24 h. The TMT-LC–MS/MS-based proteomics approach was used to quantify the differential proteomes across brain tissue, and the results were further analyzed by ingenuity pathway analysis to explore canonical pathways and the relationship involved in the uploaded data. Upon quantification, we found that 96 secreted proteins that were identified in the ICH 24-h group were significantly different those in the control group (P < 0.05); among these proteins, 57 increased and 39 decreased in abundance. Bioinformatic analyses of differentially expressed proteins demonstrated that the protein localization and ERK1 and ERK2 cascade were the top two biological processes with the highest concentrations of differentially proteins. The top protein-protein action network with high confidence levels of protein was the albumin and ERK signaling pathways. Albumin, ERK, and p-ERK were assessed in brain tissue by western blot analysis, and higher expression levels of albumin and p-ERK were observed in the ICH group. Our proteomic results highlight important change in the biological processes of ERK1 and ERK2 cascade, which are possible targets for future interventions of ICH. To our knowledge, this study provides in-depth analysis of ICH in brain tissue, and we propose 96 new biomarker candidates for ICH, including albumin and ERK. The online version of this article (10.1007/s12031-018-1206-z) contains supplementary material, which is available to authorized users.
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影响因子：
--
作者：
Hu X;Tao C;Gan Q;Zheng J;Li H;You C
通讯作者：
You C
影响因子：
3.8
作者：
Ren, Changhong;Guingab-Cagmat, Joy;Ding, Yuchuan
通讯作者：
Ding, Yuchuan
影响因子：
6
作者：
Morotti A;Marini S;Lena UK;Crawford K;Schwab K;Kourkoulis C;Ayres AM;Edip Gurol M;Viswanathan A;Greenberg SM;Anderson CD;Rosand J;Goldstein JN
通讯作者：
Goldstein JN
影响因子：
4.1
作者：
Karsy, Michael;Brock, Andrea;Park, Min S.
通讯作者：
Park, Min S.
DOI：
10.1212/nxi.0000000000000428
发表时间：
2018-03
期刊：
Neurology(R) neuroimmunology & neuroinflammation
影响因子：
--
作者：
Boehme AK;Comeau ME;Langefeld CD;Lord A;Moomaw CJ;Osborne J;James ML;Martini S;Testai FD;Woo D;Elkind MSV
通讯作者：
Elkind MSV