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CROSSTALKS AMONG SIGNAL TRANSDUCTION SYSTEMS IN APOPTOSIS IN RELATION WITH DEVELOPMENT DIFFERENTIATION AND AGING

细胞凋亡中与发育分化和衰老相关的信号转导系统之间的串扰

基本信息

批准号：
07457125
负责人：
KITO Shozo
金额：
$ 4.16万
依托单位：
University of the Air
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-07457125/
关键词：
estrogen kainic acid AP-1-DNA binding activity CA^<2+>insulin-like growth factor Immunohistochemistry dot blotting in situ hybridization 海馬ジヒドロピリジン系Ca拮抗薬 hepatocyte growth factor mRNA

项目摘要

Estrogen is deeply associated not only with development and differentiational of neuronal cells, but also with rescue mechanisms of injured or aging neurons. Our foregoing studies revealed that estrogen caused increase of the survival rate of rat hippocampal culture neurons at concentrations of 10^<-6>-10^<-9>, while depressed the survival at higher concetrations. Basing on these results, mechanisms of neuroprotective effects of estrogen were studied on kainic acid-injured brains.Immunohistochemical studies with use of monoclonal antibody against estrogen receptor showed marked increase of estrogen receptor-like immunoreactivities not only in the limbic system, but also in the wide areas of the cerebral cortesses. Such results were also confirmed through in situ hybridization experiments for estrogen receptor mRNA.Estrogen injection prior to a systemic administration of kainic acid-induced expression of neurotrophic factor and their mRNAs such as HGF,IGF I and II,as observed by dot blotting analysis, immunohistochemistry as well as in situ hybridization.Through a separate experiment with single injection of estrogen, we confirmed that estrogen increased AP-1-DNA binding activity with time course up to 120 min. when observed by gel shift assay method.These results suggested that estrogen playd roles in neuronal repair with successive proceses of increased estrogen receptors, elevation of AP-1-DNA binding activity, induction of IGF I mRNA.Neuronally differentiated PC12 cells by NGF have estrogen receptors. We noticed estrogen lenpthened the survival of PC12 cells when added together with NGF.

雌激素不仅与神经细胞的发育和分化密切相关，而且与损伤或老化神经元的拯救机制密切相关。我们的前期研究表明，雌激素在10 ~ 10 μ g/ml浓度范围内可使培养的大鼠海马神经元存活率增加<-6><-9>，而在更高浓度范围内则使其存活率降低。用抗雌激素受体单克隆抗体进行免疫组织化学研究，结果表明雌激素受体样免疫反应不仅在边缘系统，而且在大脑皮质的广泛区域均明显增强。通过斑点印迹分析、免疫组织化学和原位杂交观察，在红藻氨酸全身给药前注射雌激素诱导神经营养因子及其mRNA如HGF、IGF I和II的表达，通过单独注射雌激素的实验，我们用凝胶迁移分析法证实，雌激素增加AP-1-DNA结合活性的时间过程长达120分钟。这些结果表明，雌激素通过增加雌激素受体，提高AP-1-DNA结合活性，NGF诱导的神经分化的PC 12细胞具有雌激素受体。我们注意到当雌激素与NGF共同作用时，可以延长PC 12细胞的存活。