Interleukin-1 stimulates glutamate uptake in glial cells by accelerating membrane tracking of Na+/K+-ATPase via actin depolymerization
Interleukin-1 stimulates glutamate uptake in glial cells by accelerating membrane tracking of Na+/K+-ATPase via actin depolymerization
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DOI：
10.1128/mcb.02159-07
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发表时间：
2008-05-01
影响因子：
5.3
通讯作者：
Harada, Takayuki
中科院分区：
文献类型：
--
作者：
Namekata, Kazuhiko;Harada, Chikako;Harada, Takayuki
白细胞介素-1 (IL-1) 是缺血、创伤和慢性神经退行性疾病引起的脑损伤的介质。 IL-1 还具有防止谷氨酸神经毒性引起的神经元细胞死亡的保护作用。然而，IL-1 作用的细胞机制仍未解决。在哺乳动物视网膜中，谷氨酸/天冬氨酸转运蛋白 (GLAST) 是一种 Na+ 依赖性、主要谷氨酸转运蛋白，定位于 Muller 胶质细胞，GLAST 的缺失会导致青光眼性视网膜变性（T. Harada、C. Harada、K. Nakamura、H. A. Quah、A. Okumura、K. Namekata、T. Saeki、M. Aihara， H. Yoshida、A. Mitani 和 K. Tanaka、J. Clin。调查。 117：1763-1770，2007）。我们在此表明，IL-1 通过涉及增加膜 Na+/K+-ATP 酶定位的机制来增加 Miller 细胞中谷氨酸的摄取，这是抵消 Na+-谷氨酸共转运所需的。 IL-1 激活 p38 丝裂原激活蛋白激酶 (MAPK)/capase 11 通路，从而破坏肌动蛋白细胞骨架的稳定性，从而允许 Na+/K+-ATPase 膜重新分布。此外，IL-1 预处理可通过 p38 MAPK 信号传导保护视网膜神经元免受谷氨酸神经毒性。我们的观察表明，IL-1 通过调节胶质神经元网络的功能，充当潜在的神经保护剂。
Interleukin-1 (IL-1) is a mediator of brain injury induced by ischemia, trauma, and chronic neurodegenerative disease. IL-1 also has a protective role by preventing neuronal cell death from glutamate neurotoxicity. However, the cellular mechanisms of IL-1 action remain unresolved. In the mammalian retina, glutamate/ aspartate transporter (GLAST) is a Na+-dependent, major glutamate transporter localized to Muller glial cells, and loss of GLAST leads to glaucomatous retinal degeneration (T. Harada, C. Harada, K. Nakamura, H. A. Quah, A. Okumura, K. Namekata, T. Saeki, M. Aihara, H. Yoshida, A. Mitani, and K. Tanaka, J. Clin. Investig. 117:1763-1770, 2007). We show here that IL-1 increases glutamate uptake in Miller cells by a mechanism that involves increased membrane Na+/K+-ATPase localization, required for counteracting the Na+-glutamate cotransport. IL-1 activated the p38 mitogen-activated protein kinase (MAPK)/capase 11 pathway, which destabilizes the actin cytoskeleton allowing Na+/K+-ATPase membrane redistribution. Furthermore, pretreatment with IL-1 protected retinal neurons from glutamate neurotoxicity through p38 MAPK signaling. Our observations suggested that IL-1 acts as a potential neuroprotective agent by modulating the functions of the glia-neuron network.