NEW HORIZON OF NEURON-ASTROCYTE INTERACTION : NEUROTROPHICACTIVITY OF L-SERINE
神经元-星形胶质细胞相互作用的新视野:L-丝氨酸的神经营养活性
基本信息
- 批准号:12680764
- 负责人:
- 金额:$ 2.37万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2000
- 资助国家:日本
- 起止时间:2000 至 2001
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The overall aim of the project was to determine the physiological significance of astrocyte-derived L-Ser on the surival and development of CNS neurons in vivo. The hypothesis to be tested is that astrocyte-specific expression of 3PGDH, an enzyme catalyzing the initial step, of L-Ser biosynthesis in animal cells, is the molecular mechanism underlying neurotrophic action of L-Ser on CNS neurons. In the project, we set our effort to understand the molecular basis of astrocyte-specific expression of 3PGDH gene. We first isolated and sequenced a BAC clone which contains the mouse 3PGDH gene. Based on this structural information, we then examined promoter activity of the gene. We found using a reporter gene assay system that I.8 kb region upstream from the initiation codon in the 5'-flanking sequence directs high-level expression of reporter in astrocytes. We are now trying to identify sequence responsible for astrocyte-specific transcriptional activation by deletion of this region. In parallel with this promoter analysis, our effort was also directed to establish transgenic mice with ectopic expression of 3PGDH cDNA in CNS neurons. We constructed the transgene in which rat 3pGDH cDNA could be expressed under the control of neuron-specific promoter, Founder mice were recently obtained and we are now selecting lines with high-level neuronal expression of the cDNA. We believe that these transgenic mice will be a useful tool for testing our hypothesis.
该项目的总体目标是确定星形胶质细胞来源的L-Ser对体内CNS神经元存活和发育的生理意义。待检验的假设是,星形胶质细胞特异性表达3 PGDH(一种催化动物细胞中L-Ser生物合成的初始步骤的酶)是L-Ser对CNS神经元的神经营养作用的分子机制。本课题旨在研究3 PGDH基因在星形胶质细胞特异性表达的分子基础。我们首先分离并测序了含有小鼠3 PGDH基因的BAC克隆。基于这些结构信息,我们随后检测了该基因的启动子活性。利用报告基因分析系统,我们发现在星形胶质细胞中,5 '侧翼序列起始密码子上游1.8kb区域指导报告基因的高水平表达。我们现在正试图通过删除该区域来确定负责星形胶质细胞特异性转录激活的序列。与此启动子分析平行,我们的努力也是针对建立转基因小鼠与异位表达的3 PGDH cDNA在中枢神经系统神经元。我们构建了大鼠3 pGDH cDNA在神经元特异性启动子控制下表达的转基因,最近获得了Founder小鼠,我们正在选择具有高水平神经元表达cDNA的品系。我们相信,这些转基因小鼠将是一个有用的工具,为检验我们的假设。
项目成果
期刊论文数量(17)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Sugishita H, Mitoma J, Furuya S et al.: "L-Serine regulates the activities of microglial cells that express very low level of 3-phosphoglycerate dehydrogenase, an enzyme for L-serine biosynthesis"J. Neurosci. Res.. 64. 392-401 (2001)
Sugishita H、Mitoma J、Furuya S 等人:“L-丝氨酸调节小胶质细胞的活性,这些细胞表达非常低水平的 3-磷酸甘油酸脱氢酶,这是一种用于 L-丝氨酸生物合成的酶”J.
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Sugishita H, Mitoma J, Furuya S et al.: "L-Serine regulates the activities of microglial cells that express very low level of 3-phosphoglycerate...."J. Neurosci. Res.. 64. 392-401 (2001)
Sugishita H、Mitoma J、Furuya S 等人:“L-丝氨酸调节表达极低水平 3-磷酸甘油酸的小胶质细胞的活性......”J.
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Yamasaki, M., Yamada, K., Furuya, S, Mitoma, J., Hirabayashi, Y, and Watanabe M: "3-Phosphoglycerate dehydrogenase (3PGDH), a key enzyme for L-serine biosynthesis, is preferentially expressed in the radial glia/astrocyte lineage and olfactory ensheathing
Yamasaki, M.、Yamada, K.、Furuya, S、Mitoma, J.、Hirabayashi, Y 和 Watanabe M:“3-磷酸甘油酸脱氢酶 (3PGDH) 是 L-丝氨酸生物合成的关键酶,优先在
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Okudaira S., Ikeda, Y, Kondo, S., Furuya, S., Hirabayashi, Y, Koyano, T., Saito, Y., and Umezawa, K: "Inhibition of acidic sphingomyelinase by xanthone compounds isolated from Gracinia speciosa"J. Enzyme Inhib.. 15. 129-138 (2000)
Okudaira S.、Ikeda, Y、Kondo, S.、Furuya, S.、Hirabayashi, Y、Koyano, T.、Saito, Y. 和 Umezawa, K:“从 Gracinia spiosa 中分离出的呫吨酮化合物对酸性鞘磷脂酶的抑制”
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Furuya,S.,Tabata,T.,Mitoma,J., et al.,: "L-Ser and Gly serve as major astroglia-derived trophic factors for cerebellar Purkinje neurons."Proceedings of the National Academy of Science USA.. 97. 11528-11533 (2000)
Furuya,S.、Tabata,T.、Mitoma,J. 等人:“L-Ser 和 Gly 作为小脑浦肯野神经元的主要星形胶质细胞来源的营养因子。”美国国家科学院院刊。
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FURUYA Shigeki其他文献
FURUYA Shigeki的其他文献
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{{ truncateString('FURUYA Shigeki', 18)}}的其他基金
Physiological roles of liver de novo serine biosynthesis in adaptation to protein starvation
肝脏从头丝氨酸生物合成在适应蛋白质饥饿中的生理作用
- 批准号:
26660116 - 财政年份:2014
- 资助金额:
$ 2.37万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Early protein restriction impacts gene/protein expression and function in mature brain
早期蛋白质限制会影响成熟大脑中的基因/蛋白质表达和功能
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26292071 - 财政年份:2014
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$ 2.37万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Comparative studies on the risk of sensorimotor gating deficits in animal models of early amino acid/protein malnutrition.
早期氨基酸/蛋白质营养不良动物模型中感觉运动门控缺陷风险的比较研究。
- 批准号:
22380078 - 财政年份:2010
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$ 2.37万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Functional analysis of mouse 3-phosphoglycerate dehydrogenase (Phgdh) gene by using gene targeting
利用基因打靶技术对小鼠 3-磷酸甘油酸脱氢酶 (Phgdh) 基因进行功能分析
- 批准号:
14580756 - 财政年份:2002
- 资助金额:
$ 2.37万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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