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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(MAPKs)包括c-jun氨基末端激酶(JNK)和细胞外信号调节激酶(ERK)，参与细胞内响应各种细胞外信号的通路。为了比较JNK和ERK这两种激酶在神经发育过程中的不同作用，我们研究了它们活性形式在体内分布的差异。鸡胚胎第4天(E4)脊髓腹侧脑室带出现磷酸化ERK(p-ERK)阳性细胞。从E6开始，它们出现在灰质中，然后在白质中大量定位。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，E6出现p-ERK阳性的小细胞。随后，背角的阳性细胞数量一过性增加，然后在E10时显著减少。在E7，运动神经元也瞬时表达p-ERK。相比之下，…此外，在E3的早期投射轴突中可观察到p-JNK的表达。随后，在E5和E8，p-JNK在脊髓白质轴索中的表达增加。胚胎13岁时，p-JNK在白质轴突中的表达减弱，而在灰质的细胞核中出现强阳性表达。这些数据显示了这两种激酶的不同分布。我们还利用发育中的下丘脑细胞的原代培养，研究了MAP激酶在性激素诱导的神经发育变化中的参与。雌二醇-17β(E_2)不能增加JNK的活性，但能增加ERK的活性。E2还改变了突触蛋白L免疫反应阳性神经元的分布，显著增加了突触蛋白L免疫反应斑点(突触素L斑点)的面积。E_2拮抗剂ICI182.780、放线菌素D和放线菌素不能抑制E_2诱导的突触素L点状突触面积的增加。相反，E_2-牛血清白蛋白能有效增加突触L点状突触的面积。ERK抑制剂U0126使突触蛋白L点状突触面积显著减少。并能抑制E_2和E_2-BSA引起的突触素L点状突触面积的增加。所有这些结果表明，E2可以通过包括ERK级联在内的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在神经发育中的活体作用提供了一个框架。较少