Dexras1, a small GTPase, is required for glutamate-NMDA neurotoxicity.
Dexras1, a small GTPase, is required for glutamate-NMDA neurotoxicity.
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Dexras1是一种小的GTPase，是谷氨酸-NMDA神经毒性所必需的。
DOI：
10.1523/jneurosci.1497-12.2013
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发表时间：
2013-02-20
期刊：
影响因子：
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通讯作者：
Kim SF
中科院分区：
文献类型：
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作者：
Chen Y;Khan RS;Cwanger A;Song Y;Steenstra C;Bang S;Cheah JH;Dunaief J;Shindler KS;Snyder SH;Kim SF
Dexras 1是一种主要定位于大脑的小G蛋白，通过合成糖皮质激素地塞米松转录上调。它与Ras亚家族具有密切的同源性，但不同之处在于Dexras 1含有延伸的7 kDa C-末端尾。我们实验室以前的研究表明，NMDA受体激活，通过NO和Dexras 1，生理刺激DMT 1，主要的铁进口商。膜渗透性铁螯合剂显著降低NMDA兴奋毒性，表明Dexras 1介导的铁内流在NMDA/NO介导的细胞死亡中起关键作用。我们在这里报告，铁流入引起的一氧化氮，但不是由其他促凋亡刺激，如H2 O2或星形孢菌素。小鼠Dexras 1基因缺失可减弱体内分离的原代皮层神经元和视网膜神经节细胞中NO介导的细胞死亡因此，Dexras 1似乎通过NO和铁内流介导NMDA引起的神经毒性。
Dexras1, a small G-protein localized predominantly to the brain, is transcriptionally upregulated by the synthetic glucocorticoid dexamethasone. It has close homology to the Ras subfamily, but differs in that Dexras1 contains an extended 7 kDa C-terminal tail. Previous studies in our laboratory showed that NMDA receptor activation, via NO and Dexras1, physiologically stimulates DMT1, the major iron importer. A membrane permeable iron chelator substantially reduces NMDA-excitotoxicity suggesting that Dexras1-mediated iron influx plays a crucial role in NMDA/NO-mediated cell death. We here report that iron influx is elicited by nitric oxide but not by other pro-apoptotic stimuli such as H2O2 or staurosporine. Deletion of Dexras1 in mice attenuates NO-mediated cell death in dissociated primary cortical neurons and retinal ganglion cells in vivo. Thus Dexras1 appears to mediate NMDA-elicited neurotoxicity via NO and iron influx.