A neuroproteomic and systems biology analysis of rat brain post intracerebral hemorrhagic stroke
A neuroproteomic and systems biology analysis of rat brain post intracerebral hemorrhagic stroke
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DOI：
10.1016/j.brainresbull.2014.02.005
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发表时间：
2014-03-01
影响因子：
3.8
通讯作者：
Ding, Yuchuan
中科院分区：
文献类型：
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作者：
Ren, Changhong;Guingab-Cagmat, Joy;Ding, Yuchuan
脑出血（ICH）是一种毁灭性的中风形式，在全球范围内导致高死亡率和残疾率。尽管已经假设大部分IHC损伤发生在亚急性期，通过一系列复杂的病理生理级联介导，但ICH中涉及的分子机制尚未得到系统表征。在了解损伤和恢复潜在机制的最佳方法中，通过蛋白质组学/系统生物学平台进行蛋白质动力学评估是针对机制研究和生物标志物识别优化的主要技术之一。蛋白质组学方法可以提供一个以生物标志物为中心的框架，从该框架中鉴定参与中风后脑损伤的病理生理过程的候选生物标志物。在这项工作中，神经蛋白质组学的方法（LC-MS/MS）被应用于研究蛋白质的表达改变，诱导脑出血大鼠模型的脑组织损伤后3小时。还获得了来自假手术和局灶性缺血模型的数据并用于比较。基于差异表达的蛋白质谱，进行系统生物学分析以鉴定相关的细胞过程和相关的相互作用图谱。对3小时脑裂解液进行LC-MS/MS分析后，出血组织和假组织之间有86种蛋白质差异表达。此外，38个蛋白质在缺血和假手术组织中差异表达。在全局通路分析的水平上，出血性卒中蛋白被证明参与自噬、缺血、坏死、凋亡、钙蛋白酶激活和细胞因子分泌。此外，缺血性卒中蛋白与细胞死亡、缺血、炎症、氧化应激、caspase激活和凋亡性损伤有关。总之，在这项研究中确定的蛋白质组学反应提供了有关参与特定病理途径的靶蛋白的关键信息。(C)由Elsevier Inc.出版。
Intracerebral hemorrhage (ICH) is a devastating form of stroke leading to a high rate of death and disability worldwide. Although it has been hypothesized that much of the IHC insult occurs in the subacute period mediated via a series of complex pathophysiological cascades, the molecular mechanisms involved in ICH have not been systematically characterized. Among the best approaches to understand the underlying mechanisms of injury and recovery, protein dynamics assessment via proteomics/systems biology platforms represent one of the cardinal techniques optimized for mechanisms investigation and biomarker identification. A proteomics approach may provide a biomarker focused framework from which to identify candidate biomarkers of pathophysiological processes involved in brain injury after stroke. In this work, a neuroproteomic approach (LC-MS/MS) was applied to investigate altered expression of proteins that are induced in brain tissue 3 h after injury in a rat model of ICH. Data from sham and focal ischemic models were also obtained and used for comparison. Based on the differentially expressed protein profile, systems biology analysis was conducted to identify associated cellular processes and related interaction maps. After LC-MS/MS analysis of the 3 h brain lysates, 86 proteins were differentially expressed between hemorrhagic and sham tissues. Furthermore, 38 proteins were differentially expressed between ischemic and sham tissues. On the level of global pathway analysis, hemorrhagic stroke proteins were shown to be involved in autophagy, ischemia, necrosis, apoptosis, calpain activation, and cytokine secretion. Moreover, ischemic stroke proteins were related to cell death, ischemia, inflammation, oxidative stress, caspase activation and apoptotic injury. In conclusion, the proteomic responses identified in this study provide key information about target proteins involved in specific pathological pathways. (C) 2014 Published by Elsevier Inc.