Amyloid-beta increases acetylcholinesterase expression in neuroblastoma cells by reducing enzyme degradation

William Hu, Noah W. Gray, William Stephen Brimijoin

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Amyloid-beta (Aβ) is the principal protein constituent of 'senile plaques' and is a suspected mediator in Alzheimer's disease (AD). Senile plaques also contain acetylcholinesterase (AChE; EC 3.1.1.7), which may have a role in promoting Aβ-toxicity. We have found that Aβ can affect AChE expression in a neuron-like line, the N1E.115 neuroblastoma cell. When 1 μM Aβ 1-42 or 25-35 was added for 24 h to differentiating N1E.115 in culture, AChE activity increased 30-40% in adherent cells, and 100% or more in nonadherent cells. The changes in both tetrameric (G4) and monomeric (G1) AChE forms were comparable. Turnover studies indicated that the elevation of AChE activity reflected slowed AChE degradation rather than accelerated synthesis. With a similar time course, Aβ also increased the quantity of muscarinic receptors on the plasma membrane. Immunocytochemistry for a lysosomal membrane protein (LAMP-1) indicated no change in abundance or localization of lysosomes in treated cells. But decreased labeling by pH-sensitive fluorescent dye pointed to an impairment of lysosomal acidification. We consider that the alteration of AChE expression after Aβ-exposure could reflect lysosomal dysfunction, and might itself enhance Aβ-toxicity.

Original languageEnglish (US)
Pages (from-to)470-478
Number of pages9
JournalJournal of Neurochemistry
Volume86
Issue number2
DOIs
StatePublished - Jul 2003

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Acetylcholinesterase
Neuroblastoma
Amyloid
Toxicity
Lysosome-Associated Membrane Glycoproteins
Degradation
Acidification
Amyloid Plaques
Muscarinic Receptors
Enzymes
Cell membranes
Fluorescent Dyes
Labeling
Neurons
Thermodynamic properties
Cells
Lysosomes
Alzheimer Disease
Proteins
Immunohistochemistry

Keywords

  • Alzheimer's disease
  • Lysosomes
  • Muscarinic receptors
  • Pinocytosis
  • Protein turnover

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Amyloid-beta increases acetylcholinesterase expression in neuroblastoma cells by reducing enzyme degradation. / Hu, William; Gray, Noah W.; Brimijoin, William Stephen.

In: Journal of Neurochemistry, Vol. 86, No. 2, 07.2003, p. 470-478.

Research output: Contribution to journalArticle

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