Group I metabotropic glutamate receptor agonist DHPG modulates Kir4.1 protein and mRNA in cultured rat retinal Muller cells

被引：21

作者：

Gao, Feng ^{[1
,2
,4
,5
]}

Li, Fang ^{[2
,3
,4
]}

Miao, Yanying ^{[2
,3
,4
]}

Dong, Ling-Dan ^{[2
,3
,4
]}

Zhang, Sheng-Hai ^{[1
,2
,4
,5
]}

Wu, Jihong ^{[1
,2
,4
,5
]}

Sun, Xing-Huai ^{[1
,2
,4
,5
]}

Wang, Zhongfeng ^{[1
,2
,3
,4
,5
]}

机构：

[1] Fudan Univ, Eye & ENT Hosp, Dept Ophthalmol, Shanghai 200031, Peoples R China

[2] Fudan Univ, Inst Brain Sci, Shanghai 200031, Peoples R China

[3] Fudan Univ, Inst Neurobiol, Shanghai 200031, Peoples R China

[4] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200031, Peoples R China

[5] Fudan Univ, Shanghai Key Lab Visual Impairment & Restorat, Shanghai 200031, Peoples R China

来源：

NEUROSCIENCE LETTERS | 2015年 / 588卷

关键词：

DHPG; Kir4.1; protein; mRNA; Cultured retinal Muller cells; Gliosis;

D O I：

10.1016/j.neulet.2014.12.048

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Muller cell gliosis is a general response in a variety of pathological alternations of the retina, which is characterized by the upregulated expression of glial fibrillary acidic protein (GFAP) and the downregulation of membrane K+ conductance. We have demonstrated that downregulation of Kir currents in Muller cells in an experimental glaucoma model is due to activation of group I metabotropic glutamate receptor (mGluR I) by glutamate, which contributes to Muller cell gliosis. Here, whether and how activation of mGluR I modulate membrane Kir4.1 protein internalization and Kir4.1 mRNA expression were investigated in purified cultured rat retinal Muller cells using immunocytochemistry, Western blot and real-time PCR techniques. DHPG (10 mu M, a selective mGluR I agonist) treatment induced Muller cell gliosis, as evidenced by enhanced GFAP expression. Although total Kir4.1 proteins extracted from the DHPG-treated cells kept unchanged, Kir4.1 proteins in the cell membrane compartment were significantly decreased, which was prior to the change of GFAP in time course. In addition, DHPG (10 and 100 mu M) treatment induced a transient decrease in Kir4.1 mRNA expression in the cells. All these results suggest that activation of mGluR I by DHPG may decrease the number of functional Kir4.1 channels in purified cultured rat retinal Muller cells through modulating Kir4.1 protein and mRNA, thus contributing to Muller cell gliosis. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

引用

页码：12 / 17

页数：6

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