β淀粉样蛋白来源的扩散性配体对胞外信号调节激酶活性的影响

摘要

Aβ-derived diffusible ligands reduced the level of phosphorylated ERK 1/2.The results of immu-noblotting showed that when hippocampal neurons were treated with 500nmol/L Aβ-derived diffusible ligands , the phosphorylation levels of ERK 1/2 were all significantly reduced at different time;Aβ-derived diffusible ligands influenced the phosphorylation levels of ERK 1/2 in different parts differently .Aβ-derived diffusible ligands had significant different influences on the phosphorylation levels of ERK 1/2 in the cell membrane , cytoplasm and nucle-us depending on time;Aβ-derived diffusible ligands affected ERK 1/2 signaling pathway through extrasynaptic N -methyl-D-aspartic acid receptors .The phosphorylation levels of ERK 1/2 were both significantly reduced when merely activating extrasynaptic N -methyl-D-aspartic acid receptors or given Aβ-derived diffusible ligands pre-viously and then activating extrasynaptic N -methyl -D-aspartic acid receptors; APP mice spent more time to find the platform in the Morris Water Maze test and have lower level of phosphorylated ERK 1/2 in hippocampus .%β淀粉样蛋白来源的扩散性配体降低细胞外信号调节激酶的磷酸化水平，免疫印迹结果显示在培养的海马神经元上，给予500 nmol/L的可溶性β淀粉样蛋白寡聚体，作用不同时间均降低了胞外信号调节激酶的磷酸化水平；可溶性β淀粉样蛋白寡聚体对细胞不同部位胞外信号调节激酶磷酸化水平影响不同，并且对细胞质、细胞膜、细胞核中胞外信号调节激酶磷酸化水平的影响在时间上呈现明显的差异；β淀粉样蛋白来源的扩散性配体通过突触外N-甲基-D-天冬氨酸受体影响胞外信号调节激酶信号通路，单独激活突触外的N-甲基-D-天冬氨酸受体或给予β淀粉样蛋白来源的扩散性配体后再激活突触外的N-甲基-D-天冬氨酸受体，胞外信号调节激酶的磷酸化水平均明显降低；水迷宫实验显示，转入淀粉样前体蛋白基因的小鼠要花更多时间找到目标平台，其海马胞外信号调节激酶磷酸化水平显著降低。