Enhanced Aβ(1-40) production in endothelial cells stimulated with fibrillar Aβ(1-42).
Enhanced Aβ(1-40) production in endothelial cells stimulated with fibrillar Aβ(1-42).
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DOI：
10.1371/journal.pone.0058194
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Rifkind JM
中科院分区：
文献类型：
--
作者：
Rajadas J;Sun W;Li H;Inayathullah M;Cereghetti D;Tan A;de Mello Coelho V;Chrest FJ;Kusiak JW;Smith WW;Taub D;Wu JC;Rifkind JM
阿尔茨海默病患者脑中淀粉样蛋白的积累是由39- 43-氨基酸淀粉样β蛋白（Aβ）的加工改变引起的。淀粉样蛋白（Aβ1-42）升高的机制被认为是淀粉样前体蛋白（APP）的过度表达、APP裂解为Aβ的增强以及Aβ从中枢神经系统（CNS）的清除减少。我们在此报告了Aβ刺激对内皮细胞作用的研究。我们在内皮细胞系Hep-1中通过Western印迹分析观察到一种有趣的、前所未有的反馈效应，涉及Aβ1-42纤维诱导的APP合成。我们通过流式细胞术和荧光显微镜进一步观察到Aβ1-40的表达增加。这种现象对于在有血清和无血清的情况下生长的培养物都是可重复的。在前一种情况下，流式细胞术显示Aβ1-40的蓄积不如无血清条件下明显。免疫荧光染色进一步证实了这些观察结果。还报道了对纤维状Aβ1-42处理的细胞反应，涉及eNOS上调和自噬增加。
Amyloid accumulation in the brain of Alzheimer’s patients results from altered processing of the 39- to 43-amino acid amyloid β protein (Aβ). The mechanisms for the elevated amyloid (Aβ1–42) are considered to be over-expression of the amyloid precursor protein (APP), enhanced cleavage of APP to Aβ, and decreased clearance of Aβ from the central nervous system (CNS). We report herein studies of Aβ stimulated effects on endothelial cells. We observe an interesting and as yet unprecedented feedback effect involving Aβ1–42 fibril-induced synthesis of APP by Western blot analysis in the endothelial cell line Hep-1. We further observe an increase in the expression of Aβ1–40 by flow cytometry and fluorescence microscopy. This phenomenon is reproducible for cultures grown both in the presence and absence of serum. In the former case, flow cytometry reveals that Aβ1–40 accumulation is less pronounced than under serum-free conditions. Immunofluorescence staining further corroborates these observations. Cellular responses to fibrillar Aβ1–42 treatment involving eNOS upregulation and increased autophagy are also reported.
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影响因子：
3.7
作者：
Jaeger PA;Pickford F;Sun CH;Lucin KM;Masliah E;Wyss-Coray T
通讯作者：
Wyss-Coray T
影响因子：
4.2
作者：
Cecchi, Cristina;Fiorillo, Claudia;Liguri, Gianfranco
通讯作者：
Liguri, Gianfranco
影响因子：
4.8
作者：
Ju, H;Zou, R;Venema, RC
通讯作者：
Venema, RC
影响因子：
82.9
作者：
Deane, R;Yan, SD;Zlokovic, B
通讯作者：
Zlokovic, B
影响因子：
2.1
作者：
Armstrong, Richard A.
通讯作者：
Armstrong, Richard A.