Secretion and accumulation of Aβ by brain vascular smooth muscle cells from AβPP-Swedish transgenic mice
Secretion and accumulation of Aβ by brain vascular smooth muscle cells from AβPP-Swedish transgenic mice
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DOI：
10.1093/jnen/62.6.685
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发表时间：
2003-06-01
影响因子：
3.2
通讯作者：
Mazur-Kolecka, B
中科院分区：
文献类型：
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作者：
Frackowiak, J;Miller, DL;Mazur-Kolecka, B
在过表达含有Swedish突变（AbetaPP-Swe）的人淀粉样蛋白-β前体蛋白（AbetaPP）的转基因Tg 2576小鼠中，阿尔茨海默氏症淀粉样蛋白-β沉积在神经胶质细胞和脑血管中。因为Tg 2576小鼠中的AbetaPP转基因位于PrP启动子之后，所以所有淀粉样蛋白-P，包括血管淀粉样蛋白，被认为是神经元来源的。我们研究了转基因APPP在Tg 2576小鼠脑血管平滑肌细胞中的表达。我们发现，脑血管平滑肌细胞过表达人AbetaPP-Swe约4倍的小鼠AbetaPP的生理水平，培养的细胞分泌丰富的Abeta 1 -40和Abeta 1 -42，并形成细胞内的Abeta-immunoreactive颗粒。在第一次或第二次传代时，从14月龄小鼠获得的培养物中含有细胞内Abeta的细胞百分比和细胞内Abeta的量显著高于从4月龄小鼠获得的培养物。在培养的细胞衰老过程中，来自4个月和14个月大的小鼠的细胞中Abeta和AbetaPP的C-末端片段的细胞内积累增加。来自Tg 2576小鼠的血管肌细胞似乎是Abeta细胞内积累的有价值的模型。我们认为，血管肌肉细胞可能参与脑血管淀粉样蛋白的生产在Tg 2576小鼠。
Alzheimer amyloid-beta is deposited in the neuropil and in brain blood vessels in transgenic Tg2576 mice that overexpress human amyloid-beta precursor protein (AbetaPP) containing the Swedish mutation (AbetaPP-Swe). Because the AbetaPP transgene in Tg2576 mice is placed behind the PrP promoter, all amyloid-P, including vascular amyloid, is considered to be of neuronal origin. We studied the expression of the transgenic APPP in smooth muscle cells cultured from brain blood vessels from Tg2576 mice. We found that brain vascular smooth muscle cells overexpressed human AbetaPP-Swe approximately 4 times the physiological levels of mouse AbetaPP The cultured cells secreted abundant Abeta1-40 and Abeta1-42 and formed intracellular Abeta-immunoreactive granules. The percentage of cells containing intracellular Abeta and the amount of intracellular Abeta were significantly higher in cultures obtained from 14-month-old than from 4-month-old mice, as tested on first or second passages. During cell senescence in culture, intracellular accumulation of Abeta and C-terminal fragments of AbetaPP increased in cells derived from both 4- and 14-month-old mice. Vascular muscle cells from Tg2576 mice appear to be a valuable model of the intracellular accumulation of Abeta. We suggest that vascular muscle cells may be involved in the production of cerebrovascular amyloid in Tg2576 mice.