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新生大鼠皮质培养星形胶质细胞中β淀粉样肽(25 - 35)对纤连蛋白的调节作用

Fibronectin modulation by A beta amyloid peptide (25-35) in cultured astrocytes of newborn rat cortex.

作者信息

Moreno-Flores M T, Martín-Aparicio E, Salinero O, Wandosell F

机构信息

Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autonoma de Madrid, Cantoblanco-Madrid 28049, Spain.

出版信息

Neurosci Lett. 2001 Nov 13;314(1-2):87-91. doi: 10.1016/s0304-3940(01)02286-8.

Abstract

Fibronectin appears to be present in Senile Plaques of Alzheimer's disease brains. These senile or neuritic plaques are surrounded by dystrophic neurites, activated microglia and reactive astrocytes. The purpose of this work was to establish if a direct correlation exists between the production of Fibronectin (FN) by astrocytes and the presence of amyloid, analysing the modification of this protein produced after the treatment of cultured astrocytes with amyloid peptide (25-35). Our data showed that the addition of previously polymerised A beta-peptide to cultured astrocytes induced a marked increase in FN immunoreactivity that is in part dependent on phosphatases 2A or phosphatase 1, since was partially inhibited by okadaic acid. The increased amount of FN did not appear to be associated to any specific single isoform of which are mainly present in the rat brain. Our data suggest that in vivo FN accumulated in senile plaques may be the result, at least in part, of the response of reactive astrocyte to the presence of amyloid peptide. The importance of FN up-regulation in vivo, as part of a 'positive' response of the astrocytes to produce molecules that favours neurite outgrowth, is discussed.

摘要

纤连蛋白似乎存在于阿尔茨海默病患者大脑的老年斑中。这些老年斑或神经炎斑被营养不良的神经突、活化的小胶质细胞和反应性星形胶质细胞所包围。这项工作的目的是通过分析用淀粉样肽(25 - 35)处理培养的星形胶质细胞后产生的这种蛋白质的修饰情况,来确定星形胶质细胞产生的纤连蛋白(FN)与淀粉样蛋白的存在之间是否存在直接关联。我们的数据表明,向培养的星形胶质细胞中添加预先聚合的Aβ肽会导致FN免疫反应性显著增加,这部分依赖于磷酸酶2A或磷酸酶1,因为它会被冈田酸部分抑制。FN增加的量似乎与大鼠脑中主要存在的任何特定单一亚型无关。我们的数据表明,体内老年斑中积累的FN可能至少部分是反应性星形胶质细胞对淀粉样肽存在的反应结果。本文还讨论了体内FN上调的重要性,它是星形胶质细胞产生有利于神经突生长分子的“积极”反应的一部分。

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