Predominant expression of nuclear activator protein-1 complex with DNA binding activity following systemic administration of N-methyl-d-aspartate in dentate granule cells of murine hippocampus
Predominant expression of nuclear activator protein-1 complex with DNA binding activity following systemic administration of N-methyl-d-aspartate in dentate granule cells of murine hippocampus
复制标题
全身给予 N-甲基-d-天冬氨酸后，小鼠海马齿状颗粒细胞中具有 DNA 结合活性的核激活蛋白 1 复合物的主要表达
DOI：
10.1016/s0306-4522(99)00117-7
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发表时间：
1999
期刊：
影响因子：
3.3
通讯作者：
T. Kitayama
中科院分区：
文献类型：
--
作者：
Y. Yoneda;K. Ogita;Y. Azuma;N. Kuramoto;T. Manabe;T. Kitayama
全身给予N-甲基-d-天冬氨酸（100mg/kg，腹腔注射）导致小鼠海马齿状回颗粒细胞层中转录因子激活蛋白-1的优先但短暂的表达，1小时后最高达到700%，4小时内对CA1和CA3亚区锥体细胞层的表达没有显着影响。预先给予 10mg/kg 的 N-甲基-d-天冬氨酸通道阻断剂地佐西平可完全阻止这种增强作用。相比之下，红藻氨酸（40mg/kg，腹腔注射）除了增强 CA1 和 CA3 亚区以及齿状回的神经元细胞层中的结合外，还增强了锥体细胞层和颗粒细胞层周围邻近区域的激活蛋白 1 DNA 结合。光学显微镜分析显示，在给药后 14 天，红藻氨酸（而非 N-甲基-d-天冬氨酸）诱导 CA1 和 CA3 亚区中锥体细胞的显着损失，但不影响齿状颗粒细胞。 V8 蛋白酶和 supershift 的有限蛋白水解，以及使用抗 c-Fos 和 c-Jun 抗体的免疫印迹测定，总是支持由不同伙伴蛋白组成的激活蛋白 1 复合物的 N-甲基-d-天冬氨酸和红藻氨酸的差异表达。此外，二维电泳和免疫印迹分析显示，海马中几种核蛋白的表达与抗 c-Fos 抗体发生免疫反应，其分子量和等电点明显不同于 c-Fos 本身对红藻氨酸的反应，但与 N-甲基-d-天冬氨酸没有反应。这些结果表明，体内N-甲基-d-天冬氨酸信号主要通过与小鼠海马齿状回颗粒细胞中红藻氨酸信号不同的分子机制转导到细胞核中表达激活蛋白-1复合物。
The systemic administration of N-methyl-d-aspartate (100mg/kg, i.p.) resulted in preferential but transient expression of the transcription factor activator protein-1 in the granule cell layers of the dentate gyrus in the murine hippocampus by maximally 700% 1h later, without markedly affecting that in the pyramidal cell layers of the CA1 and CA3 subfields for 4h. The potentiation was completely prevented by prior administration of the N-methyl-d-aspartate channel blocker dizocilpine at 10mg/kg. By contrast, kainate (40mg/kg, i.p.) potentiated activator protein-1 DNA binding in adjacent areas around the pyramidal and granule cell layers, in addition to potentiating that in neuronal cell layers of the CA1 and CA3 subfields and the dentate gyrus. Light microscopic analysis revealed that kainate, but not N-methyl-d-aspartate, induced marked losses of the pyramidal cells in the CA1 and CA3 subfields, without affecting the dentate granule cells, for 14days after administration. Limited proteolysis by V8 protease and supershift, as well as immunoblotting assays using antibodies against c-Fos and c-Jun, invariably gave support for differential expression by N-methyl-d-aspartate and kainate of the activator protein-1 complex consisting of different partner proteins. Moreover, two-dimensional electrophoresis followed by immunoblotting analysis revealed the expression of several nuclear proteins immunoreactive with the anti-c-Fos antibody at molecular weights and isoelectric points clearly different from those of c-Fos itself in response to kainate, but not N-methyl-d-aspartate, in the hippocampus. These results suggest that in vivoN-methyl-d-aspartate signals are predominantly transduced into cell nuclei to express activator protein-1 complex through molecular mechanisms different from those for kainate signals in the granule cells of the dentate gyrus in the murine hippocampus.