Promoter activity of the gene encoding the beta-amyloid precursor protein is up-regulated by growth factors, phorbol ester, retinoic acid and interleukin-1

Debomoy K. Lahiri, Christina Nall

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

Abnormalities in gene regulation of the β-amyloid precursor protein ( βAPP) might be an important factor in the neuropathology of Alzheimer's disease. We analyzed the effects of nerve growth factor (NGF), basic fibroblast growth factor (bFGF), phorbol 12-myristate 13-acetate (PMA), interleukin-1 (IL-1) and retinoic acid (RA) on promoter activity of the βAPP gene. To investigate the effect of these factors on promoter activity, we used two fusion plasmids which contain sequences of -489 and -415 base pairs (bp), respectively, from the transcription start site of the βAPP gene. The truncated regions of the promoter were linked upstream to a reporter gene, chloramphenicol acetyl transferase (CAT). Promoter activity was tested by transient transfection of fusion plasmids in PC12 cells using the electroporation method (960 μF at 350 V). We report that the treatment of PC12 cells with either NGF, bFGF, PMA, IL-1 or RA stimulated the activity of the βAPP promoter. The treatment of cells with either NGF or bFGF resulted in a higher degree of stimulation in the basal level of promoter activity than when cells were treated with either PMA, IL-1 or RA. The deletion of sequences between -489 to -416 by had no significant effect on promoter activity. The treatment of cells with these factors for a duration of 4 days prior to transfection with the plasmids is necessary for the stimulatory effect. The cells that were only treated with any of these factors after transfection showed no significant change in the basal level of promoter activity. We conclude that certain growth factors and a cytokine could enhance the basal level of promoter activity of the βAPP gene, suggesting a possible participation of a growth-factor(s)-mediated transcription element in the control of gene expression of βAPP.

Original languageEnglish (US)
Pages (from-to)233-240
Number of pages8
JournalMolecular Brain Research
Volume32
Issue number2
DOIs
StatePublished - Sep 1995

Keywords

  • Alzheimer's disease
  • Differentiation
  • Gene regulation
  • Growth factor
  • Interleukin-1
  • PC12 cell
  • Promoter
  • Retinoic acid
  • β-Amyloid precursor protein

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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