Neurotoxicity of sodium salicylate to the spiral ganglion neurons: GABAA receptor regulates NMDA receptor by Fyn-dependent phosphorylation
Neurotoxicity of sodium salicylate to the spiral ganglion neurons: GABAA receptor regulates NMDA receptor by Fyn-dependent phosphorylation
复制标题
水杨酸钠对螺旋神经节神经元的神经毒性：GABA(A)受体通过Fyn依赖性磷酸化调节NMDA受体
DOI：
10.1007/s00359-019-01339-z
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发表时间：
2019-08-01
影响因子：
2.1
通讯作者：
Su, Jiping
中科院分区：
文献类型：
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作者：
Liu, Peiqiang;Qin, Danxue;Su, Jiping
本研究旨在观察水杨酸钠（SS）对大鼠耳蜗螺旋神经节神经元兴奋性毒性过程中GABA（A）受体对N-甲基-D-天冬氨酸（NMDA）受体的调节作用。Western blot结果显示，SS通过影响GABA（A）受体，降低NMDA受体2B亚单位（NR 2B）表面蛋白的表达，但对总蛋白含量无明显影响。Y1472和S1480是NR 2B中重要的磷酸化位点，SS下调Y1472的Fyn依赖性磷酸化，但与S1480的CK 2（Casein Kinase 2）依赖性磷酸化无关，从而通过GABA（A）受体调节NMDA受体的表面分布和内化。这些结果表明，通过共激活GABA（A）受体的兴奋和抑制之间的动态平衡的修改模式可以减弱兴奋性NMDA受体在SS的作用下，通过抑制Fyn依赖的磷酸化Y1472。
The purpose of this study was to observe the regulatory effects of GABA(A) (gamma-aminobutyric acid A) receptor on the N-methyl-d-aspartate (NMDA) receptor during excitotoxicity in spiral ganglion neurons in the rat cochlea induced by sodium salicylate (SS). Western blot illustrated SS decreased the expression of NMDA receptor 2B subunit (NR2B) surface protein through affecting GABA(A) receptor, but the total protein content did not significantly change. Y1472 and S1480 are important phosphorylation sites in NR2B, SS downregulated the Fyn-dependent phosphorylation of Y1472 in a manner not related to the CK2 (Casein Kinase 2) dependent phosphorylation of S1480, thus regulating the surface distribution and internalization of NMDA receptor through GABA(A) receptor. These results suggest that the modified pattern of dynamic balance between excitation and inhibition by coactivation of the GABA(A) receptor can attenuate the excitatory NMDA receptor under the action of SS, via inhibiting the Fyn-dependent phosphorylation of Y1472.