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

Jayakumar Rajadas, Wenchao Sun, Hai Li, Mohammed Inayathullah, Damiano Cereghetti, Aaron Tan, Valeria de Mello Coelho, Francis J. Chrest, John W. Kusiak, Wanli Wei Smith, Dennis Taub, Joseph C. Wu, Joseph M. Rifkind

Research output: Contribution to journalArticlepeer-review

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 (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.

Original languageEnglish (US)
Article numbere58194
JournalPloS one
Volume8
Issue number3
DOIs
StatePublished - Mar 7 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Enhanced Aβ<sub>1-40</sub> Production in Endothelial Cells Stimulated with Fibrillar Aβ<sub>1-42</sub>'. Together they form a unique fingerprint.

Cite this