NDRG2 Protects the Brain from Excitotoxicity by Facilitating Interstitial Glutamate Uptake
NDRG2 Protects the Brain from Excitotoxicity by Facilitating Interstitial Glutamate Uptake
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NDRG2 通过促进间质谷氨酸摄取来保护大脑免受兴奋性毒性
DOI：
10.1007/s12975-019-00708-9
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发表时间：
2019-06
影响因子：
6.9
通讯作者：
Li Yan
中科院分区：
文献类型：
--
作者：
Yin Anqi;Guo Hang;Tao Liang;Cai Guohong;Wang Yazhou;Yao Libo;Xiong Lize;Zhang Jian;Li Yan
谷氨酸是一种重要的神经递质，负责兴奋性突触传递，并被星形胶质细胞上的钠依赖性兴奋性氨基酸转运蛋白（EAATs）摄取，以维持突触的稳态。在这里，我们报道了N-myc下游调控基因2 (NDRG2)，一个已知的肿瘤抑制因子，是促进星形胶质细胞谷氨酸摄取和保护大脑免受缺血后谷氨酸兴奋毒性所必需的。NDRG2敲除（NDRG2−/−）小鼠表现出脑间质谷氨酸增加和星形胶质细胞谷氨酸摄取减少。NDRG2控制eaat介导的谷氨酸摄取进入星形胶质细胞的能力需要NDRG2与Na+/K+- atp酶β1相互作用并促进其功能，而Na+/K+- atp酶β1肽可破坏Na+/K+- atp酶β1。NDRG2缺失或Na+/K+- atp酶β1肽治疗显著增加谷氨酸刺激下的神经元死亡和缺血后脑损伤加重。我们的研究结果表明，NDRG2在促进星形胶质细胞从间质空间摄取谷氨酸和保护大脑免受谷氨酸兴奋毒性方面起着关键作用。
Glutamate is a prominent neurotransmitter responsible for excitatory synaptic transmission and is taken up by sodium-dependent excitatory amino acid transporters (EAATs) on astrocytes to maintain synaptic homeostasis. Here, we report that N-myc downstream regulated gene 2 (NDRG2), a known tumor suppressor, is required to facilitate astroglial glutamate uptake and protect the brain from glutamate excitotoxicity after ischemia. NDRG2 knockout (Ndrg2−/−) mice exhibited an increase in cerebral interstitial glutamate and a reduction in glutamate uptake into astrocytes. The ability of NDRG2 to control EAAT-mediated glutamate uptake into astrocytes required NDRG2 to interact with and promote the function of Na+/K+-ATPase β1, which could be disrupted by a Na+/K+-ATPase β1 peptide. The deletion of NDRG2 or treatment with the Na+/K+-ATPase β1 peptide significantly increased neuronal death upon a glutamate challenge and aggravated brain damage after ischemia. Our findings demonstrate that NDRG2 plays a pivotal role in promoting astroglial glutamate uptake from the interstitial space and protecting the brain from glutamate excitotoxicity.
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影响因子：
25
作者：
Fan, Xuelai;Jin, Wu Yang;Lu, Jie;Wang, Jin;Wang, Yu Tian
通讯作者：
Wang, Yu Tian
星形胶质细胞兴奋性神经递质转运蛋白 GLT1 的突触前调节。
影响因子：
16.2
作者：
Yang, Yongjie;Gozen, Oguz;Watkins, Andrew;Lorenzini, Ileana;Lepore, Angelo;Gao, Yuanzheng;Vidensky, Svetlana;Brennan, Jean;Poulsen, David;Park, Jeong Won;Jeon, Noo Li;Robinson, Michael B.;Rothstein, Jeffrey D.
通讯作者：
Rothstein, Jeffrey D.
影响因子：
14.5
作者：
Behrens, P. F.;Franz, P.;Landwehrmeyer, G. B.
通讯作者：
Landwehrmeyer, G. B.
影响因子：
25
作者：
Murphy-Royal, Ciaran;Dupuis, Julien P.;Oliet, Stephane H. R.
通讯作者：
Oliet, Stephane H. R.
脑出血大鼠模型脑组织中NDRG2的时空表达：初步研究
影响因子：
2.5
作者：
Gao, Lingfeng;Li, Xiang;Chen, Gang
通讯作者：
Chen, Gang