Neuroprotective effects of daphnetin against NMDA receptor-mediated excitotoxicity.
Neuroprotective effects of daphnetin against NMDA receptor-mediated excitotoxicity.
复制标题
瑞香素对 NMDA 受体介导的兴奋性毒性的神经保护作用
DOI：
10.3390/molecules190914542
复制
发表时间：
2014-09-15
期刊：
影响因子：
--
通讯作者：
Zhao MG
中科院分区：
文献类型：
--
作者：
Yang L;Yang Q;Zhang K;Li YJ;Wu YM;Liu SB;Zheng LH;Zhao MG
谷氨酸的积累可过度激活N-甲基-d-天冬氨酸（NMDA）受体，引起兴奋性毒性。瑞香素（Dap）是一种香豆素衍生物，是一种蛋白激酶抑制剂，具有抗氧化和神经保护作用。然而，关于Dap对谷氨酸诱导的兴奋性毒性的神经保护作用知之甚少。我们评估了在原代培养的皮层神经元对NMDA诱导的兴奋性毒性的神经保护活性。用Dap预处理显著防止NMDA诱导的神经元细胞损失。Dap通过调节Bcl-2和Bax表达的平衡，抑制神经元凋亡。此外，Dap预处理逆转了NMDA受体NR 2B的上调，抑制了NMDA诱导的细胞内Ca ~（2+）超载。此外，Dap可预防小鼠大脑中动脉闭塞2 h再灌注24 h引起的脑缺血损伤。结果表明，Dap通过抑制含NR 2B的NMDA受体和随后的钙超载来防止兴奋性毒性。
The accumulation of glutamate can excessively activate the N-methyl-d-aspartate (NMDA) receptors and cause excitotoxicity. Daphnetin (Dap), a coumarin derivative, is a protein kinase inhibitor that exhibits antioxidant and neuroprotective properties. However, little is known about the neuroprotective effects of Dap on glutamate-induced excitotoxicity. We evaluated the neuroprotective activities in the primary cultured cortical neurons against NMDA-induced excitotoxicity. Pretreatment with Dap significantly prevented NMDA-induced neuronal cell loss. Dap significantly inhibited the neuronal apoptosis by regulating balance of Bcl-2 and Bax expression. Furthermore, pretreatment of Dap reversed the up-regulation of NR2B-containing NMDA receptors and inhibited the intracellular Ca2+ overload induced by NMDA exposure. In addition, Dap prevented cerebral ischemic injury in mice induced via a 2 h middle cerebral artery occlusion and a 24 h reperfusion in vivo. The findings suggest that Dap prevents the excitotoxicity through inhibiting the NR2B-containing NMDA receptors and the subsequent calcium overload in cultured cortical neurons.
登录
查看更多内容
影响因子：
4.7
作者：
Wu Y;Peng H;Cui M;Whitney NP;Huang Y;Zheng JC
通讯作者：
Zheng JC
DOI：
10.1073/pnas.0903546106
发表时间：
2009-06-16
影响因子：
11.1
作者：
Stanika, Ruslan I.;Pivovarova, Natalia B.;Andrews, S. Brian
通讯作者：
Andrews, S. Brian
影响因子：
3.3
作者：
Vander Jagt TA;Connor JA;Weiss JH;Shuttleworth CW
通讯作者：
Shuttleworth CW
影响因子：
5.3
作者：
Liu, Yitao;Wong, Tak Pan;Wang, Yu Tian
通讯作者：
Wang, Yu Tian
影响因子：
6.7
作者：
Sun, Mingna;Hu, Jinfeng;Liu, Gang
通讯作者：
Liu, Gang