The protective role of (-)-epigallocatechin-3-gallate in thrombin-induced neuronal cell apoptosis and JNK-MAPK activation
The protective role of (-)-epigallocatechin-3-gallate in thrombin-induced neuronal cell apoptosis and JNK-MAPK activation
复制标题
(-)-表没食子儿茶素-3-没食子酸酯在凝血酶诱导的神经元细胞凋亡和 JNK-MAPK 激活中的保护作用
DOI：
10.1097/wnr.0000000000000363
复制
发表时间：
2015-05-06
期刊：
影响因子：
1.7
通讯作者：
Cui, Guiyun
中科院分区：
文献类型：
--
作者：
He, Qianqian;Bao, Lei;Cui, Guiyun
（-）-表没食子儿茶素-3-没食子酸酯（EGCG）是绿色茶的主要多酚成分，具有抗炎和抗氧化特性，并提供针对中枢神经系统疾病的神经保护。然而，目前尚不清楚EGCG是否可能对脑出血具有神经保护作用。在这项研究中，我们使用了一个简化的凝血酶神经毒性体外模型，以测试是否表没食子儿茶素没食子酸酯提供神经保护凝血酶相关的毒性。原代皮层神经元暴露于凝血酶（100 U/ml）引起剂量依赖性和时间依赖性的细胞毒性。细胞计数试剂盒8和乳酸脱氢酶用于监测神经元暴露于凝血酶或EGCG后以及EGCG预处理后的细胞活力。流式细胞仪分析和蛋白质印迹证明凝血酶诱导的神经元变性通过凋亡发生。浓度为25 μ M的EGCG通过抑制c-Jun-N-末端激酶（JNK）磷酸化显著消除凝血酶诱导的毒性并防止细胞凋亡，JNK抑制剂SP 600125减少凝血酶诱导的caspase 3激活和细胞凋亡。这些数据表明，表没食子儿茶素没食子酸酯可能有保护作用，对凝血酶诱导的神经细胞凋亡抑制JNK的激活，导致半胱天冬酶3切割。表没食子儿茶素没食子酸酯（EGCG）是一种新型的神经保护剂。版权所有（C）2015威科医疗集团All rights reserved.
(-)-Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green tea, has anti-inflammatory and antioxidant properties and provides neuroprotection against central nervous system diseases. Yet, it is not known whether EGCG may be neuroprotective against intracerebral hemorrhage. In this study, we used a simplified in-vitro model of thrombin neurotoxicity to test whether EGCG provides neuroprotection against thrombin-associated toxicity. Exposure of primary cortical neurons to thrombin (100 U/ml) caused dose-dependent and time-dependent cytotoxicity. Cell Counting Kit 8 and lactate dehydrogenase were used to monitor cell viability after exposure of neurons to thrombin or EGCG and after EGCG pretreatment. Flow cytometric analysis and western blotting demonstrated that thrombin-induced neuron degeneration occurs through apoptosis. A concentration of 25 mu M EGCG significantly abolished thrombin-induced toxicity and prevented apoptosis by suppressing c-Jun-N-terminal kinase (JNK) phosphorylation, and the JNK inhibitor SP600125 reduced thrombin-induced caspase 3 activation and apoptosis. These data suggest that EGCG may have protective effects against thrombin-induced neuroapoptosis by inhibiting the activation of JNK, leading to caspase 3 cleavage. EGCG is a novel candidate neuroprotective agent against intracerebral hemorrhage-induced neurotoxicity. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.