title: Enhanced Aβ(1-40) production in endothelial cells stimulated with fibrillar Aβ(1-42).
abstract: 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 (Aβ(1-42)) 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 Aβ(1-42) 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 Aβ(1-40) 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 Aβ(1-40) accumulation is less pronounced than under serum-free conditions. Immunofluorescence staining further corroborates these observations. Cellular responses to fibrillar Aβ(1-42) treatment involving eNOS upregulation and increased autophagy are also reported.
authors.affiliation: Biomaterials and Advanced Drug Delivery Laboratory, Stanford University School of Medicine, Stanford, California, United States of America. jayraja@stanford.edu
authors.forename: Jayakumar
authors.initials: J
authors.lastname: Rajadas
authors.forename: Wenchao
authors.initials: W
authors.lastname: Sun
authors.forename: Hai
authors.initials: H
authors.lastname: Li
authors.forename: Mohammed
authors.initials: M
authors.lastname: Inayathullah
authors.forename: Damiano
authors.initials: D
authors.lastname: Cereghetti
authors.forename: Aaron
authors.initials: A
authors.lastname: Tan
authors.forename: Valeria
authors.initials: V
authors.lastname: de Mello Coelho
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Chrest
authors.forename: John W
authors.initials: JW
authors.lastname: Kusiak
authors.forename: Wanli Wei
authors.initials: WW
authors.lastname: Smith
authors.forename: Dennis
authors.initials: D
authors.lastname: Taub
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Rifkind
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000494:pharmacology* / Q000648:ultrastructure; D001343:Autophagy; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000494:pharmacology* / Q000648:ultrastructure
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D052250:Nitric Oxide Synthase Type III