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Significance of microglia derived plasmin-generating proteases in the nervous system

小胶质细胞衍生的纤溶酶生成蛋白酶在神经系统中的意义

基本信息

批准号：
07680864
负责人：
NAKAJIMA Kazuyuki
金额：
$ 1.34万
依托单位：
National Institute of Neuroscience
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
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-07680864/
关键词：
microglia plasminogen plasminogen activator

项目摘要

The aim of this study was to study (1) action mechanism of plasminogen in the neuron, (2) production of microglia-derived proteases in the brain, (3) regulatory factor of secretory proteases from microglia.(1) We studied the action of plasminogen and prodiction of inositol tri-phosphate (IP3) or protein-phosphorylations in the cultured neuron derived from neonatal rat brain, and found taht plasminogen induces a transiient increase of IP3 and causes a tyrosine- phosphorylation in a certain protein(>100kDa) of cultured neuron. However, since, in the latter case, the degree of phophorylation was very low and delicate, it is necessary to be confirmed by trustworthy study.(2) Using the transection model of rat facial nerve, we showed taht plasminogen activator activity was transiently induced in axotomized facial nucleus. The plasminogen activator was characterized and identified as urokinase type plasminogen activator (uPA) from the results of response to the uPA inhibitor, amiloride, and of the molecular weight. The cell producing uPA in the facial nucleus was sugested to be microglia. Plasminogen was also suggested to increase in axotomized facial nucleus.(3) We surveyed the factors which elevate the amounts of plasminogen and/or plasminogen activator in microglia, and found that neurotrophin has an ability to promote the secretion of plasminogen and uPA.Nerve growth factor, brain-derived neurotrophic factor, neurotrophon-3 and neurotrophin-4/5 were comparable for the increasing effect. The neurotrophin had a capacity to decrease the release of nitric oxide from microglia. The analysis of specific receptor for the neurotrophins in cultured microglia revealed the expression of trk A,trk B and trk C at both mRNA and protein level.

本研究的目的是研究（1）神经元中纤溶酶原的作用机制，（2）脑中小胶质细胞衍生蛋白酶的产生，（3）小胶质细胞分泌蛋白酶的调节因子。（1）我们研究了新生大鼠培养神经元中纤溶酶原的作用和肌醇三磷酸（IP3）或蛋白质磷酸化的产生研究发现，纤溶酶原会诱导 IP3 短暂增加，并导致培养神经元的某种蛋白质（>100kDa）发生酪氨酸磷酸化。然而，由于后一种情况的磷酸化程度非常低且脆弱，因此有必要通过可靠的研究来证实。(2)利用大鼠面神经横断模型，我们发现在轴突面神经核中短暂诱导了纤溶酶原激活剂活性。根据对uPA抑制剂阿米洛利的反应结果和分子量，对纤溶酶原激活剂进行表征并鉴定为尿激酶型纤溶酶原激活剂(uPA)。面核中产生 uPA 的细胞被认为是小胶质细胞。 (3)我们调查了小胶质细胞中纤溶酶原和/或纤溶酶原激活剂含量升高的因素，发现神经营养蛋白具有促进纤溶酶原和uPA分泌的能力。神经生长因子、脑源性神经营养因子、神经营养蛋白-3和神经营养蛋白-4/5 增加效果具有可比性。神经营养素具有减少小胶质细胞释放一氧化氮的能力。对培养的小胶质细胞中神经营养素特异性受体的分析揭示了trk A、trk B和trk C在mRNA和蛋白质水平上的表达。