A Proximal Gene Promoter Region for the β-Amyloid Precursor Protein Provides a Link between Development, Apoptosis, and Alzheimer's Disease

Debomoy Lahiri, C. Ghosh, Y. W. Ge

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Abnormalities in regulation of the β-amyloid precursor protein (APP) gene might be a crucial factor in Alzheimer's disease (AD). Our aim is to study the role of a specific proximal APP promoter element under the apoptotic condition. Our transfection studies with APP promoter deletion constructs indicate that each cell type differently regulates promoter activity. The minimum region that was sufficient to drive basal promoter activity in neuronal PC12 and neuroblastoma SK-N-SH cells was -75/+104 and -47/+104 bp, respectively. In SK-N-SH cells, the -47/+104 construct displayed the highest promoter activity, and the -75/-46 region acted as a negative regulatory element. Results from the gel electrophoretic mobility shift assay (EMSA) indicate that the -75/-46 region binds to a distinct DNA-protein complex with nuclear protein(s) from HeLa, PC12, NIH-3T3, and neuroblastoma cells. EMSA results from HeLa cells, which were stimulated by serum starvation (SR), indicate a significant induction in the signal of the DNA-protein complex from controls. EMSA results from PC12 cells, which were subjected to hypoxia, indicate a significant reduction in the signal. Our results suggest that the -75/-46 region binds to a protein that is upregulated in serum starvation, and downregulated in hypoxia. Because serum starvation contributes to the induction of apoptosis, these results suggest a role of the 30-bp proximal APP promoter element in enhanced apoptotic neuronal cell death.

Original languageEnglish
Pages (from-to)643-647
Number of pages5
JournalAnnals of the New York Academy of Sciences
Volume1010
DOIs
StatePublished - 2003

Fingerprint

Amyloid beta-Protein Precursor
Genetic Promoter Regions
Electrophoretic mobility
Alzheimer Disease
Electrophoretic Mobility Shift Assay
Starvation
Genes
Apoptosis
Assays
Neuroblastoma
Serum
NIH 3T3 Cells
Proteins
PC12 Cells
DNA
Cell death
Nuclear Proteins
HeLa Cells
Transfection
Cell Death

Keywords

  • Aging
  • Apoptosis
  • Dementia
  • Gel shift assay
  • Gene regulation
  • Neurodegeneration
  • Neuronal proteins
  • Neurons
  • Promoter
  • Transcription

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

@article{2c8526c5478e4d19962ce44dbad4ad04,
title = "A Proximal Gene Promoter Region for the β-Amyloid Precursor Protein Provides a Link between Development, Apoptosis, and Alzheimer's Disease",
abstract = "Abnormalities in regulation of the β-amyloid precursor protein (APP) gene might be a crucial factor in Alzheimer's disease (AD). Our aim is to study the role of a specific proximal APP promoter element under the apoptotic condition. Our transfection studies with APP promoter deletion constructs indicate that each cell type differently regulates promoter activity. The minimum region that was sufficient to drive basal promoter activity in neuronal PC12 and neuroblastoma SK-N-SH cells was -75/+104 and -47/+104 bp, respectively. In SK-N-SH cells, the -47/+104 construct displayed the highest promoter activity, and the -75/-46 region acted as a negative regulatory element. Results from the gel electrophoretic mobility shift assay (EMSA) indicate that the -75/-46 region binds to a distinct DNA-protein complex with nuclear protein(s) from HeLa, PC12, NIH-3T3, and neuroblastoma cells. EMSA results from HeLa cells, which were stimulated by serum starvation (SR), indicate a significant induction in the signal of the DNA-protein complex from controls. EMSA results from PC12 cells, which were subjected to hypoxia, indicate a significant reduction in the signal. Our results suggest that the -75/-46 region binds to a protein that is upregulated in serum starvation, and downregulated in hypoxia. Because serum starvation contributes to the induction of apoptosis, these results suggest a role of the 30-bp proximal APP promoter element in enhanced apoptotic neuronal cell death.",
keywords = "Aging, Apoptosis, Dementia, Gel shift assay, Gene regulation, Neurodegeneration, Neuronal proteins, Neurons, Promoter, Transcription",
author = "Debomoy Lahiri and C. Ghosh and Ge, {Y. W.}",
year = "2003",
doi = "10.1196/annals.1299.118",
language = "English",
volume = "1010",
pages = "643--647",
journal = "Annals of the New York Academy of Sciences",
issn = "0077-8923",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - A Proximal Gene Promoter Region for the β-Amyloid Precursor Protein Provides a Link between Development, Apoptosis, and Alzheimer's Disease

AU - Lahiri, Debomoy

AU - Ghosh, C.

AU - Ge, Y. W.

PY - 2003

Y1 - 2003

N2 - Abnormalities in regulation of the β-amyloid precursor protein (APP) gene might be a crucial factor in Alzheimer's disease (AD). Our aim is to study the role of a specific proximal APP promoter element under the apoptotic condition. Our transfection studies with APP promoter deletion constructs indicate that each cell type differently regulates promoter activity. The minimum region that was sufficient to drive basal promoter activity in neuronal PC12 and neuroblastoma SK-N-SH cells was -75/+104 and -47/+104 bp, respectively. In SK-N-SH cells, the -47/+104 construct displayed the highest promoter activity, and the -75/-46 region acted as a negative regulatory element. Results from the gel electrophoretic mobility shift assay (EMSA) indicate that the -75/-46 region binds to a distinct DNA-protein complex with nuclear protein(s) from HeLa, PC12, NIH-3T3, and neuroblastoma cells. EMSA results from HeLa cells, which were stimulated by serum starvation (SR), indicate a significant induction in the signal of the DNA-protein complex from controls. EMSA results from PC12 cells, which were subjected to hypoxia, indicate a significant reduction in the signal. Our results suggest that the -75/-46 region binds to a protein that is upregulated in serum starvation, and downregulated in hypoxia. Because serum starvation contributes to the induction of apoptosis, these results suggest a role of the 30-bp proximal APP promoter element in enhanced apoptotic neuronal cell death.

AB - Abnormalities in regulation of the β-amyloid precursor protein (APP) gene might be a crucial factor in Alzheimer's disease (AD). Our aim is to study the role of a specific proximal APP promoter element under the apoptotic condition. Our transfection studies with APP promoter deletion constructs indicate that each cell type differently regulates promoter activity. The minimum region that was sufficient to drive basal promoter activity in neuronal PC12 and neuroblastoma SK-N-SH cells was -75/+104 and -47/+104 bp, respectively. In SK-N-SH cells, the -47/+104 construct displayed the highest promoter activity, and the -75/-46 region acted as a negative regulatory element. Results from the gel electrophoretic mobility shift assay (EMSA) indicate that the -75/-46 region binds to a distinct DNA-protein complex with nuclear protein(s) from HeLa, PC12, NIH-3T3, and neuroblastoma cells. EMSA results from HeLa cells, which were stimulated by serum starvation (SR), indicate a significant induction in the signal of the DNA-protein complex from controls. EMSA results from PC12 cells, which were subjected to hypoxia, indicate a significant reduction in the signal. Our results suggest that the -75/-46 region binds to a protein that is upregulated in serum starvation, and downregulated in hypoxia. Because serum starvation contributes to the induction of apoptosis, these results suggest a role of the 30-bp proximal APP promoter element in enhanced apoptotic neuronal cell death.

KW - Aging

KW - Apoptosis

KW - Dementia

KW - Gel shift assay

KW - Gene regulation

KW - Neurodegeneration

KW - Neuronal proteins

KW - Neurons

KW - Promoter

KW - Transcription

UR - http://www.scopus.com/inward/record.url?scp=1342347850&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1342347850&partnerID=8YFLogxK

U2 - 10.1196/annals.1299.118

DO - 10.1196/annals.1299.118

M3 - Article

C2 - 15033805

AN - SCOPUS:1342347850

VL - 1010

SP - 643

EP - 647

JO - Annals of the New York Academy of Sciences

JF - Annals of the New York Academy of Sciences

SN - 0077-8923

ER -