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Functions of c-Jun N-terminal Kinase (JNK) during neural development

c-Jun N 末端激酶 (JNK) 在神经发育过程中的功能

基本信息

批准号：
13680884
负责人：
OHTANI-KANEKO Ritsuko
金额：
$ 2.18万
依托单位：
St. Marianna University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680884/
关键词：
MAP Kinase JNK ERK chick embryo neuron synapsin l estrogen hypothalamus p38 synapsin I エストラジオール共焦点レーザー顕微鏡アポトーシスラクタシスチン antisense oligonucleotide MAPK PC12h細胞プロテアソーム

项目摘要

Mitogen-activated protein kinases (MAPKs) including c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) are involved in the intracellular pathways that respond to various extracellular signals. To compare the different contribution of these two kinases, JNK and ERK, during the neural development, we studied the differences in the in vivo distribution of their active forms. In the spinal cord of chick embryos, phosphorylated ERK (p-ERK) positive cells appeared in the ventral ventricular zone on embryonic day 4 (E4). From E6 onward, they appeared in the gray matter and were then localized abundantly in the white matter. A double labeling method revealed that these p-ERK positive cells included oligodendrocyte precursors. In the dorsal horn, p-ERK positive small cells appeared on E6. Subsequently, the positive cells in the dorsal horn increased transiently in numberand then decreased markedly by E10. Motoneurons also expressed p-ERK transiently on E7. In contrast … More , the expression of p-JNK was observed in early-projecting axons on E3. Subsequently, on E5 and E8, the expression of p-JNK increased in the axonal tracts in the spinal white matter. By E13, the expression of p-JNK was decreased in axons in the white matter, whereas strong p-JNK expression appeared in cell nuclei in the gray matter. These data showed the different distribution of these two kinases.We also studied the involvement of MAP kinase in the sex steroids-induced changes in the neural development, using primary cultures of developing hypothalamic cells. Estradiol-17beta (E2) did not increase activity of JNK but ERK. E2 also changed the distribution of synapsin l-immunoreactivity and significantly increased the area of synapsin l-immunoreactive puncta (synapsin l-puncta). E2 antagonist ICI182.780, actinomycin D (AMD) and cychoheximde (CHX) did not suppress the E2-induced increase in the area of synapsin l-puncta. In contrast, E2-BSA was effective to increase the area of synapsin l-puncta. U0126, a inhibitor of ERK, remarkably reduced the area of synapsin l-puncta. It also suppressed the increase in area of synapsin l-puncta induced by E2 as well as E2-BSA. All these results suggested that E2 can affect developing hypothalamic neurons through a non-genomic pathway including ERK cascade. Our studies provide a framework to begin to examine the in vivo role of JNK and ERK in neural development. Less

丝裂原活化蛋白激酶（Mitogen-activated protein kinases，MAPKs）包括c-Jun N-末端激酶（c-Jun N-terminal kinase，JNK）和细胞外信号调节激酶（extracellular signal-regulated kinase，ERK），参与细胞内信号转导通路，对细胞外信号产生应答。为了比较JNK和ERK这两种激酶在神经发育过程中的不同贡献，我们研究了它们活性形式在体内分布的差异。鸡胚脊髓腹侧脑室区在胚胎第4天（E4）出现磷酸化ERK（p-ERK）阳性细胞。从E6开始，它们出现在灰质中，然后大量定位在白色物质中。双标记法显示，这些p-ERK阳性细胞包括少突胶质细胞前体。在背角，p-ERK阳性小细胞出现在E6。随后，背角内的阳性细胞数量短暂增加，到E10时明显减少。运动神经元也在E7上瞬时表达p-ERK。相比之下 ...更多信息 p-JNK在E3早期投射的轴突中有表达。随后，在E5和E8，p-JNK在脊髓白色物质的轴突束中的表达增加。到E13，p-JNK的表达在白色物质的轴突中减少，而在灰质的细胞核中出现强的p-JNK表达。这些数据表明这两种激酶的不同分布。我们还研究了MAP激酶参与性类固醇诱导的神经发育的变化，利用发育中的下丘脑细胞的原代培养。E2不增加JNK的活性，但增加ERK的活性。E2还改变了突触素l免疫反应阳性点的分布，并显著增加突触素l免疫反应阳性点的面积。E_2拮抗剂ICI 182.780、放线菌素D（AMD）和放线菌素环己酰亚胺（CHX）不能抑制E_2诱导的突触蛋白L-点面积的增加。相反，E2-BSA可有效增加突触蛋白L-点的面积。ERK抑制剂U 0126显著减少突触蛋白L-点的面积。抑制E_2和E_2-BSA诱导的突触蛋白L-点面积的增加。这些结果表明，E2可以通过ERK级联反应等非基因组途径影响发育中的下丘脑神经元。我们的研究为开始研究JNK和ERK在神经发育中的体内作用提供了一个框架。少