Nuclear factor κB/p49 is a negative regulatory factor in nerve growth factor-induced choline acetyltransferase promoter activity in PC12 cells

Tracy Toliver-Kinsky, Thomas Wood, J. R. Perez-Polo

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

A novel nuclear factor κB (NF-κB) binding site has been identified within the promoter region of the mouse gene encoding choline acetyltransferase (ChAT), the enzyme that synthesizes acetylcholine and has been implicated in the cognitive deficits associated with aging and Alzheimer's disease. This binding site, which is located within the nerve growth factor (NGF)-responsive enhancer element, was recognized by the NF-κB protein p49 but not p65 or p50. p49 from both basal forebrain and PC12 nuclear extracts interacted with this specific sequence in electrophoretic mobility shift assays. Mutation of the NF-κB site caused an increase in NGF-induced promoter activation, whereas overexpression of p49 in NGF-differentiated PC12 cells caused a decrease in endogenous ChAT enzyme activity and a decrease in promoter activity that was specifically mediated through this NF-κB binding site. Treatment of PC12 cells with NGF resulted in a drastic reduction in nuclear p49 binding to the ChAT NF-κB site after 24 h, but nuclear p49 levels were not altered, suggesting that late NGF-mediated events prevent binding of p49 to the ChAT promoter by an unknown mechanism other than nuclear translocation. Decreased ChAT expression and increased NF-κB activity in the brain are associated with aging and Alzheimer's disease. These data indicate that p49 is a negative regulator of ChAT expression and suggest a possible mechanism for aging-associated declines in cholinergic function.

Original languageEnglish (US)
Pages (from-to)2241-2251
Number of pages11
JournalJournal of Neurochemistry
Volume75
Issue number6
DOIs
StatePublished - 2000

Fingerprint

Choline O-Acetyltransferase
PC12 Cells
Nerve Growth Factor
Aging of materials
Binding Sites
Alzheimer Disease
Electrophoretic mobility
Gene encoding
Enzyme activity
Electrophoretic Mobility Shift Assay
Enzymes
Genetic Promoter Regions
Cholinergic Agents
Acetylcholine
Assays
Brain
Chemical activation
Mutation
Genes
Proteins

Keywords

  • Choline acetyltransferase
  • Nerve growth factor
  • Nuclear factor κB
  • P49/p52
  • PC12 cells
  • Promoter

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Nuclear factor κB/p49 is a negative regulatory factor in nerve growth factor-induced choline acetyltransferase promoter activity in PC12 cells. / Toliver-Kinsky, Tracy; Wood, Thomas; Perez-Polo, J. R.

In: Journal of Neurochemistry, Vol. 75, No. 6, 2000, p. 2241-2251.

Research output: Contribution to journalArticle

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