Functional activity of the novel Alzheimer's amyloid β-peptide interacting domain (AβID) in the APP and BACE1 promoter sequences and implications in activating apoptotic genes and in amyloidogenesis

Jason A. Bailey, Bryan Maloney, Yuan Wen Ge, Debomoy K. Lahiri

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Amyloid-β peptide (Aβ) plaque in the brain is the primary (post mortem) diagnostic criterion of Alzheimer's disease (AD). The physiological role(s) of Aβ are poorly understood. We have previously determined an Aβ interacting domain (AβID) in the promoters of AD-associated genes (Maloney and Lahiri, 2011. Gene. 15,doi:10.1016/j.gene.2011.06.004. epub ahead of print.). This AβID interacts in a DNA sequence-specific manner with Aβ. We now demonstrate novel Aβ activity as a possible transcription factor. Herein, we detected Aβ-chromatin interaction in cell culture by ChIP assay. We observed that human neuroblastoma (SK-N-SH) cells treated with FITC conjugated Aβ1-40 localized Aβ to the nucleus in the presence of H 2O 2-mediated oxidative stress. Furthermore, primary rat fetal cerebrocortical cultures were transfected with APP and BACE1 promoter-luciferase fusions, and rat PC12 cultures were transfected with polymorphic APP promoter-CAT fusion clones. Transfected cells were treated with different Aβ peptides and/or H 2O 2. Aβ treatment of cell cultures produced a DNA sequence-specific response in cells transfected with polymorphic APP clones. Our results suggest the Aβ peptide may regulate its own production through feedback on its precursor protein and BACE1, leading to amyloidogenesis in AD.

Original languageEnglish (US)
Pages (from-to)13-22
Number of pages10
JournalGene
Volume488
Issue number1-2
DOIs
StatePublished - Nov 15 2011

Fingerprint

Amyloid
Alzheimer Disease
Clone Cells
Cell Culture Techniques
Genes
Peptides
Protein Precursors
Fluorescein-5-isothiocyanate
Luciferases
Neuroblastoma
Chromatin
Oxidative Stress
Transcription Factors
Brain
Protein Domains

Keywords

  • Alzheimer's disease
  • Amyloid beta
  • DNA-protein interaction
  • Gene regulation
  • Transcription factor

ASJC Scopus subject areas

  • Genetics

Cite this

@article{87868a3474f443b19e407365fa5f207a,
title = "Functional activity of the novel Alzheimer's amyloid β-peptide interacting domain (AβID) in the APP and BACE1 promoter sequences and implications in activating apoptotic genes and in amyloidogenesis",
abstract = "Amyloid-β peptide (Aβ) plaque in the brain is the primary (post mortem) diagnostic criterion of Alzheimer's disease (AD). The physiological role(s) of Aβ are poorly understood. We have previously determined an Aβ interacting domain (AβID) in the promoters of AD-associated genes (Maloney and Lahiri, 2011. Gene. 15,doi:10.1016/j.gene.2011.06.004. epub ahead of print.). This AβID interacts in a DNA sequence-specific manner with Aβ. We now demonstrate novel Aβ activity as a possible transcription factor. Herein, we detected Aβ-chromatin interaction in cell culture by ChIP assay. We observed that human neuroblastoma (SK-N-SH) cells treated with FITC conjugated Aβ1-40 localized Aβ to the nucleus in the presence of H 2O 2-mediated oxidative stress. Furthermore, primary rat fetal cerebrocortical cultures were transfected with APP and BACE1 promoter-luciferase fusions, and rat PC12 cultures were transfected with polymorphic APP promoter-CAT fusion clones. Transfected cells were treated with different Aβ peptides and/or H 2O 2. Aβ treatment of cell cultures produced a DNA sequence-specific response in cells transfected with polymorphic APP clones. Our results suggest the Aβ peptide may regulate its own production through feedback on its precursor protein and BACE1, leading to amyloidogenesis in AD.",
keywords = "Alzheimer's disease, Amyloid beta, DNA-protein interaction, Gene regulation, Transcription factor",
author = "Bailey, {Jason A.} and Bryan Maloney and Ge, {Yuan Wen} and Lahiri, {Debomoy K.}",
year = "2011",
month = "11",
day = "15",
doi = "10.1016/j.gene.2011.06.017",
language = "English (US)",
volume = "488",
pages = "13--22",
journal = "Gene",
issn = "0378-1119",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Functional activity of the novel Alzheimer's amyloid β-peptide interacting domain (AβID) in the APP and BACE1 promoter sequences and implications in activating apoptotic genes and in amyloidogenesis

AU - Bailey, Jason A.

AU - Maloney, Bryan

AU - Ge, Yuan Wen

AU - Lahiri, Debomoy K.

PY - 2011/11/15

Y1 - 2011/11/15

N2 - Amyloid-β peptide (Aβ) plaque in the brain is the primary (post mortem) diagnostic criterion of Alzheimer's disease (AD). The physiological role(s) of Aβ are poorly understood. We have previously determined an Aβ interacting domain (AβID) in the promoters of AD-associated genes (Maloney and Lahiri, 2011. Gene. 15,doi:10.1016/j.gene.2011.06.004. epub ahead of print.). This AβID interacts in a DNA sequence-specific manner with Aβ. We now demonstrate novel Aβ activity as a possible transcription factor. Herein, we detected Aβ-chromatin interaction in cell culture by ChIP assay. We observed that human neuroblastoma (SK-N-SH) cells treated with FITC conjugated Aβ1-40 localized Aβ to the nucleus in the presence of H 2O 2-mediated oxidative stress. Furthermore, primary rat fetal cerebrocortical cultures were transfected with APP and BACE1 promoter-luciferase fusions, and rat PC12 cultures were transfected with polymorphic APP promoter-CAT fusion clones. Transfected cells were treated with different Aβ peptides and/or H 2O 2. Aβ treatment of cell cultures produced a DNA sequence-specific response in cells transfected with polymorphic APP clones. Our results suggest the Aβ peptide may regulate its own production through feedback on its precursor protein and BACE1, leading to amyloidogenesis in AD.

AB - Amyloid-β peptide (Aβ) plaque in the brain is the primary (post mortem) diagnostic criterion of Alzheimer's disease (AD). The physiological role(s) of Aβ are poorly understood. We have previously determined an Aβ interacting domain (AβID) in the promoters of AD-associated genes (Maloney and Lahiri, 2011. Gene. 15,doi:10.1016/j.gene.2011.06.004. epub ahead of print.). This AβID interacts in a DNA sequence-specific manner with Aβ. We now demonstrate novel Aβ activity as a possible transcription factor. Herein, we detected Aβ-chromatin interaction in cell culture by ChIP assay. We observed that human neuroblastoma (SK-N-SH) cells treated with FITC conjugated Aβ1-40 localized Aβ to the nucleus in the presence of H 2O 2-mediated oxidative stress. Furthermore, primary rat fetal cerebrocortical cultures were transfected with APP and BACE1 promoter-luciferase fusions, and rat PC12 cultures were transfected with polymorphic APP promoter-CAT fusion clones. Transfected cells were treated with different Aβ peptides and/or H 2O 2. Aβ treatment of cell cultures produced a DNA sequence-specific response in cells transfected with polymorphic APP clones. Our results suggest the Aβ peptide may regulate its own production through feedback on its precursor protein and BACE1, leading to amyloidogenesis in AD.

KW - Alzheimer's disease

KW - Amyloid beta

KW - DNA-protein interaction

KW - Gene regulation

KW - Transcription factor

UR - http://www.scopus.com/inward/record.url?scp=80053384785&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053384785&partnerID=8YFLogxK

U2 - 10.1016/j.gene.2011.06.017

DO - 10.1016/j.gene.2011.06.017

M3 - Article

C2 - 21708232

AN - SCOPUS:80053384785

VL - 488

SP - 13

EP - 22

JO - Gene

JF - Gene

SN - 0378-1119

IS - 1-2

ER -