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Function and gene expression of the high-affinity NGF receptor

高亲和力NGF受体的功能和基因表达

基本信息

批准号：
05680674
负责人：
IKEUCHI Toshihiko
金额：
$ 1.34万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05680674/
关键词：
Nerve Growth Factor NGF Receptor RT-PCR Method Differentiation of Neurons Cultured Neuronal Cell Cholinergic Neurons

项目摘要

Using a quantitative RT-PCR,we studied the regulation of trkA mRNA expression in serum-free, cultured basal forebain neurons from 17-day fetal rats. Besides increasing ChAT activities, NGF strikingly induced trkA gene expression in a time- and NGF concentration-dependent manner. Therefore, NGF might play a critical role in trkA gene expression during the development of basal forebrain cholinergic neurons. Furthermore, to investigate whether this up-regulation is connected with the trophic effects on basal forebrain cholinergic neurons, we examined the effects of some other neurotrophic agents (BDNF,NT-3, bFGF,CNTF and 40 mM KC1) upon ChAT activity and trkA gene expression. Some neurotrophic factors increased ChAT activities to the same degree as NGF,whereas they did not stimulate trkA mRNA expression so potently. NT-3 plus K252b promotes the tyrosine phosphorylation of TrkA in PC12 cells and increases ChAT activity in cultured basal forebrain cholinergic neurons like NGF.We found that NT-3 plus K252b up-regulated the level of trkA mRNA.These results suggested that the expression of trkA mRNA is regulated directly by its specific ligand NGF,rather than by neurotrophic effects upon basal forebrain cholinergic neurons and that the up-regulation is connected to a molecular event initiated by the binding of NGF to the TrkA receptor.

采用定量RT-PCR方法，研究了无血清培养的17天胎鼠基底前脑神经元中trkA mRNA表达的调控。除了增加ChAT活性外，NGF还以时间和NGF浓度依赖性方式显著诱导trkA基因表达。因此，在基底前脑胆碱能神经元发育过程中，NGF可能对trkA基因表达起关键作用。此外，为了研究这种上调是否与基底前脑胆碱能神经元的营养作用有关，我们研究了其他一些神经营养剂（BDNF，NT-3，bFGF，CNTF和40 mM KCl）对ChAT活性和trkA基因表达的影响。一些神经营养因子增加ChAT活性的程度与NGF相同，而它们没有刺激trkA mRNA的表达，所以有力。NT-3 + K252 b可促进PC 12细胞TrkA的酪氨酸磷酸化，并可增加培养的基底前脑胆碱能神经元如NGF的ChAT活性，我们发现NT-3 + K252 b可上调TrkA mRNA的表达，提示TrkA mRNA的表达受其特异性配体NGF的直接调控，而不是通过对基底前脑胆碱能神经元的神经营养作用，并且上调与由NGF与TrkA受体结合引发的分子事件有关。