Riluzole increases glutamate uptake by cultured C6 astroglial cells
Riluzole increases glutamate uptake by cultured C6 astroglial cells
复制标题
DOI：
10.1016/j.ijdevneu.2013.06.002
复制
发表时间：
2013-11-01
影响因子：
1.8
通讯作者：
Quincozes-Santos, Andre
中科院分区：
文献类型：
--
作者：
Dall'Igna, Oscar P.;Bobermin, Larissa D.;Quincozes-Santos, Andre
利鲁唑是一种被批准用于治疗肌萎缩性侧索硬化症（ALS）的药物，可能对其他神经退行性疾病和神经精神疾病有效。利鲁唑对中枢神经系统有多种作用，包括改变谷氨酸的释放和摄取，从而降低谷氨酸的细胞外水平，但这些作用的潜在机制尚不清楚。在这里，我们证明了利鲁唑刺激谷氨酸摄取并增强了C6星形胶质细胞培养中谷氨酸EAAC1转运体的表达。当利鲁唑与蛋白激酶C （PKC；双吲哚马来酰亚胺II）、磷脂酰肌醇3-激酶（PI3K; wortmannin）和成纤维细胞生长因子受体1 （FGFR1; PD173074）抑制剂共同给药时，利鲁唑对谷氨酸摄取的影响降至低于对照组。利鲁唑还能降低活性氧负荷，但对谷胱甘肽水平没有影响。本研究探讨了利鲁唑对谷氨酸代谢的三种独立细胞内通路及其作用机制。(c) 2013 isdn。Elsevier Ltd.出版。版权所有。
Riluzole is a drug approved for the treatment of amyotrophic lateral sclerosis (ALS) and may be effective for the treatment of other neurodegenerative and neuropsychiatric disorders. Riluzole exerts diverse actions on the central nervous system, including altering glutamate release and uptake, and therefore act diminishing glutamate extracellular levels, but the underlying mechanism of these actions is still unknown. Here, we demonstrate that riluzole stimulated glutamate uptake and augmented the expression of the glutamate EAAC1 transporter in C6 astroglial cell cultures. The effect of riluzole on glutamate uptake was reduced to below controls when it was co-administered with inhibitors of protein kinase C (PKC; bisindolylmaleimide II), phosphatidylinositol 3-kinase (PI3K; wortmannin) and fibroblast growth factor receptor 1 (FGFR1; PD173074). Riluzole also decreased reactive oxygen species load with no effect on glutathione levels. This study investigates three independent intracellular pathways and the mechanism of action of riluzole on glutamate metabolism. (C) 2013 ISDN. Published by Elsevier Ltd. All rights reserved.