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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >CD147, a gamma-secretase associated protein is upregulated in Alzheimer's disease brain and its cellular trafficking is affected by presenilin-2.
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CD147, a gamma-secretase associated protein is upregulated in Alzheimer's disease brain and its cellular trafficking is affected by presenilin-2.

机译：CD147是一种与γ-分泌酶相关的蛋白，在阿尔茨海默氏病大脑中被上调，其细胞运输受到早老素2的影响。

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摘要

Gamma-secretase activity has been extensively investigated due to its role in Alzheimer's disease. Here, we studied the association of CD147, a transmembrane glycoprotein belonging to the immunoglobulin family, with gamma-secretase and its expression in Alzheimer's disease and control tissues. Subcellular fractionation of postmitochondrial supernatant from rat brain on step iodixanol gradient in combination with co-immunoprecipitation using an anti-nicastrin antibody showed association of limited amount of CD147 to gamma-secretase. By immunoblotting of postnuclear pellets from Alzheimer's disease and control human brain tissues we showed that CD147 with molecular weight 75 kDa is upregulated in frontal cortex and thalamus of the Alzheimer's disease brains. Immunohistochemistry of brain tissues from Alzheimer's disease and control revealed specific upregulation of CD147 in neurons, axons and capillaries of Alzheimer's disease frontal cortex and thalamus. The effect of presenilin-1 and -2, which are the catalytic subunits of gamma-secretase, on CD147 expression and subcellular localization was analyzed by confocal microscopy in combination with flow cytometry and showed that PS2 affected the subcellular localization of CD147 in mouse embryonic fibroblast cells. We suggest that a small fraction of CD147 present in the brain is associated with the gamma-secretase, and can be involved in mechanisms dysregulated in Alzheimer's disease brain.
机译：由于γ-分泌酶活性在阿尔茨海默氏病中的作用，已被广泛研究。在这里，我们研究了CD147（一种属于免疫球蛋白家族的跨膜糖蛋白）与γ-分泌酶的关系及其在阿尔茨海默氏病和对照组织中的表达。在步骤碘克沙醇梯度条件下，将大鼠脑线粒体后上清液进行亚细胞分级分离，并结合使用抗神经钙蛋白抗体的免疫共沉淀，表明有限量的CD147与伽马分泌酶相关。通过免疫印迹阿尔茨海默氏病和控制人脑组织的核后沉淀，我们发现分子量为75 kDa的CD147在阿尔茨海默氏病大脑的额叶皮层和丘脑中被上调。来自阿尔茨海默氏病和对照的脑组织的免疫组织化学显示，阿尔茨海默氏病额叶皮层和丘脑的神经元，轴突和毛细血管中CD147特异性上调。共聚焦显微镜结合流式细胞术分析了γ-分泌酶的催化亚基presenilin-1和-2对CD147表达和亚细胞定位的影响，结果表明PS2影响了小鼠胚胎成纤维细胞CD147的亚细胞定位。细胞。我们建议大脑中存在的一小部分CD147与伽马分泌酶有关，并且可能与阿尔茨海默氏病大脑中失调的机制有关。

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