Enhanced Aβ1–40 Production in Endothelial Cells Stimulated with Fibrillar Aβ1–42

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,...

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Bibliographic Details
Published in:PloS one 2013-03, Vol.8 (3), p.e58194
Main Authors: Rajadas, Jayakumar, Sun, Wenchao, Li, Hai, Inayathullah, Mohammed, Cereghetti, Damiano, Tan, Aaron, de Mello Coelho, Valeria, Chrest, Francis J., Kusiak, John W., Smith, Wanli Wei, Taub, Dennis, Wu, Joseph C., Rifkind, Joseph M.
Format: Article
Language:English
Subjects:
Accumulation
Aging
Alzheimer's disease
Amino acids
Amyloid precursor protein
Biology
Biomedical materials
Blood-brain barrier
Brain
Brain research
Cell culture
Cell death
Central nervous system
Cytokines
Cytometry
Disease
Endothelial cells
Flow cytometry
Fluorescence
Fluorescence microscopy
Immunofluorescence
Immunology
Laboratories
Medicine
Overexpression
Oxidative stress
Peptides
Phagocytosis
Proteins
Rodents
Smooth muscle
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0058194