Aquaporin-4 deficiency down-regulates glutamate uptake and GLT-1 expression in astrocytes
Aquaporin-4 deficiency down-regulates glutamate uptake and GLT-1 expression in astrocytes
复制标题
DOI：
10.1016/j.mcn.2006.09.008
复制
发表时间：
2007-01-01
影响因子：
3.5
通讯作者：
Hu, Gang
中科院分区：
文献类型：
--
作者：
Zeng, Xiao-Ning;Sun, Xiu-Lan;Hu, Gang
水通道蛋白-4在水运输中的作用已被广泛研究，而关于其对星形胶质细胞功能的贡献的信息很少，例如对神经元能传输的作用。由于水通道蛋白4与谷氨酸转运蛋白1（GLT-1）广泛共定位，并且谷氨酸转运蛋白也具有水转运特性，我们采用原代培养的AQP4基因敲除小鼠星形胶质细胞，研究了水通道蛋白4对谷氨酸转运蛋白的调节作用。结果表明，缺乏水通道蛋白-4下调星形胶质细胞表达GLT-1，但不谷氨酸/天冬氨酸转运蛋白（GLAST）。[H-3] D，L-谷氨酸摄取分析的结果显示AQP4-/-星形胶质细胞的摄取能力较低。MTT法和LDH法检测表明，AQP4（-/-）基因型的细胞毒性较低。这些发现首次为水通道蛋白4在谷氨酸转运体功能中发挥重要作用提供了直接证据。本研究将进一步加深我们对水通道蛋白4-谷氨酰胺能生物学的理解。(c)2006年爱思唯尔公司All rights reserved.
The role of aquaporin-4 in water transport has been extensively investigated, while little information exists regarding its contribution to astrocytic functions such as the action to glutamatergic transmission. Since aquaporin-4 has been detected widely co-localized with glutamate transporter 1 (GLT-1) and glutamate transporters also present water transport properties, we investigated the regulative role of aquporin-4 on glutamate transporter using primary cultured astrocytes from aquaporin-4 knockout (AQP4(-/-)) mice. It was demonstrated that lack of aquaporin-4 down-regulated astrocytic expression of GLT-1 but not of glutamate/aspartate transporter (GLAST). The result from [H-3]D,L-glutamate uptake analysis showed a lower uptake capability in AQP4-/- astrocytes. Furthermore, MTT and LDH assays indicated less cellular toxicity induced by excessive glutamate in AQP4(-/-) genotype. These findings provide direct evidences for the first time that aquaporin-4 plays an important role in the function of glutamate transporters. And the present study will improve our understanding of aquaporin-4-glutamanergic biology. (c) 2006 Elsevier Inc. All rights reserved.