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Intracellular responses by stimulation of receptors in neurons and related cells

通过刺激神经元和相关细胞中的受体而产生细胞内反应

基本信息

批准号：
07458205
负责人：
MIYAMOTO Eishichi
金额：
$ 5.25万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07458205/
关键词：
Receptor Intracellular response Second messenger Calcium ion Enzyme activation Cultured cell Neuron Glia 初代培養細胞細胞系脳切片 CaMキナーゼ C EBPファミリー転写因子蛋白質燐酸化反応

项目摘要

Neurons and related cells in the brain receive diverse stimuli for receptors in the plasma membranes, which include nerve impulses, neurotransmitters, neuropeptides, autacoids, hormones, cytokines, and growth factors. Responses of the cells include various types such as the production of second messengers and activation of tyrosine kinases. The intracellular calcium ion (Ca^<2+>) is established to be one of second messengers and its concentration in the cells is strictly regulated. The purposes of the present study are to elucidate the intracellular responses elicited by the increase in Ca^<2+> on the basis of stimulation of receptors in the plasma membranes. We used primarily cultured neurons of the hippocampus, astrocytes from cerebrum and cultured granule cells from cerebellum, established cell lines such as PC12 cells. NG108-15 cells, C6 glioma cells, fibroblast 3Yl cells and brain slices. In an attempt to elucidate the functions of the central nervous system through Ca^<2+> signaling pathways, we examined the dynamic state of activation of Ca^<2+>/calmodulin-dependent protein kinase II (CaM kinase II) in the cell systems. We found that CaM kinase II is activated through elevation of intracellular Ca^<2+> in response to the extracellular stimuli and is involved in the cellular functions of the central nervous system, such as neuronal differentiation of PC12 cells, gene expression in astrocytes and long-term potentiation in the CAl area of the hippocampus. Ca^<2+> is also involved in the activation of mitogenactivated protein kinase in neurons and astrocytes. Furthermore, with concomitant activation of the enzyme, phosphorylation of endogenous substrates was studied.

脑内神经元及相关细胞接受质膜受体的多种刺激，包括神经冲动、神经递质、神经肽、类自身激素、激素、细胞因子、生长因子等。细胞的反应包括多种类型，如第二信使的产生和酪氨酸激酶的激活。细胞内钙离子（Ca^<2+>）被确定为第二信使之一，其在细胞内的浓度受到严格调控。本研究的目的是在刺激质膜受体的基础上阐明Ca^<2+>增加所引起的细胞内反应。我们主要使用培养的海马神经元、大脑星形胶质细胞和培养的小脑颗粒细胞，建立了PC12细胞等细胞系。NG108-15细胞、C6胶质瘤细胞、成纤维细胞3Yl细胞和脑切片。为了阐明通过Ca^<2+>信号通路中枢神经系统的功能，我们检测了细胞系统中Ca^<2+>/钙调素依赖性蛋白激酶II （calmodulin-dependent protein kinase II, CaM kinase II）的激活动态。我们发现，在细胞外刺激下，CaM激酶II通过细胞内Ca^<2+>的升高而被激活，并参与中枢神经系统的细胞功能，如PC12细胞的神经元分化、星形胶质细胞的基因表达和海马CAl区的长期增强。Ca^<2+>也参与神经元和星形胶质细胞中有丝分裂原激活蛋白激酶的激活。此外，伴随酶的激活，内源性底物的磷酸化被研究。