Global proteomic analysis of brain tissues in transient ischemia brain damage in rats.
Global proteomic analysis of brain tissues in transient ischemia brain damage in rats.
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DOI：
10.3390/ijms160611873
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发表时间：
2015-05-26
影响因子：
5.6
通讯作者：
Tsai TH
中科院分区：
文献类型：
--
作者：
Chen JH;Kuo HC;Lee KF;Tsai TH
由于动脉闭塞或低血压导致的缺血再灌注损伤导致组织缺氧伴葡萄糖剥夺，这导致内质网（ER）应激和神经元死亡。采用蛋白质组学方法鉴定了缺血性脑卒中大鼠脑组织中差异表达的蛋白质。其作用机制涉及细胞凋亡和内质网应激途径。采用双侧颈总动脉阻断法建立大鼠脑缺血再灌注损伤模型。采用双向凝胶电泳（2-DE）对脑卒中动物模型（SAM）和对照组大鼠皮层神经元蛋白质进行分离纯化和鉴定。我们的研究结果表明，SAM大鼠经历了缺血核心的脑细胞死亡。SAM大鼠和对照大鼠之间有15个蛋白质差异表达，并在体内和体外进行了分析和验证。有趣的是，这组差异表达的下调蛋白包括儿茶酚O-甲基转移酶（COMT）和组织蛋白酶D（CATD），它们与氧化应激、炎症反应和细胞凋亡有关。在缺血性中风后，一个蛋白质点，即钙视网膜蛋白（CALB 2）蛋白，表现出增加的表达。它介导SAM给药对细胞凋亡和ER应激途径的影响。我们的研究结果表明，神经元细胞的缺血性损伤增加细胞毒性和凋亡，这是伴随着持续激活的IRE1-α/TRAF2，JNK1/2，和p38 MAPK通路。蛋白质组学分析表明，CALB 2在全脑缺血性卒中期间的差异表达可能参与了ER应激诱导神经细胞凋亡的机制，其通过IRE1-α/TRAF 2复合物的形成以及JNK 1/2和p38 MAPK的激活而发生。基于这些结果，我们也提供了支持缺血再灌注相关神经元损伤的分子证据。
Ischemia-reperfusion injury resulting from arterial occlusion or hypotension in patients leads to tissue hypoxia with glucose deprivation, which causes endoplasmic reticulum (ER) stress and neuronal death. A proteomic approach was used to identify the differentially expressed proteins in the brain of rats following a global ischemic stroke. The mechanisms involved the action in apoptotic and ER stress pathways. Rats were treated with ischemia-reperfusion brain injuries by the bilateral occlusion of the common carotid artery. The cortical neuron proteins from the stroke animal model (SAM) and the control rats were separated using two-dimensional gel electrophoresis (2-DE) to purify and identify the protein profiles. Our results demonstrated that the SAM rats experienced brain cell death in the ischemic core. Fifteen proteins were expressed differentially between the SAM rats and control rats, which were assayed and validated in vivo and in vitro. Interestingly, the set of differentially expressed, down-regulated proteins included catechol O-methyltransferase (COMT) and cathepsin D (CATD), which are implicated in oxidative stress, inflammatory response and apoptosis. After an ischemic stroke, one protein spot, namely the calretinin (CALB2) protein, showed increased expression. It mediated the effects of SAM administration on the apoptotic and ER stress pathways. Our results demonstrate that the ischemic injury of neuronal cells increased cell cytoxicity and apoptosis, which were accompanied by sustained activation of the IRE1-alpha/TRAF2, JNK1/2, and p38 MAPK pathways. Proteomic analysis suggested that the differential expression of CALB2 during a global ischemic stroke could be involved in the mechanisms of ER stress-induced neuronal cell apoptosis, which occurred via IRE1-alpha/TRAF2 complex formation, with activation of JNK1/2 and p38 MAPK. Based on these results, we also provide the molecular evidence supporting the ischemia-reperfusion-related neuronal injury.
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