Toxic effects of acetylcholinesterase on neuronal and glial-like cells in vitro

F. H. Calderón, R. Von Bernhardi, G. De Ferrari, S. Luza, R. Aldunate, N. C. Inestrosa

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)

Abstract

Acetylcholinesterase (AChE), the enzyme involved in the hydrolysis of the neurotransmitter acetylcholine, has been implicated in non-cholinergic actions which may play a role in neurodegenerative diseases such as Alzheimer's disease. To study the potential cytotoxicity of brain AChE, the effects of affinity purified AChE were analyzed on neuronal (Neuro 2a) and glial-like (B12) cells. LDH release and MTT reduction assays showed that AChE was toxic; the toxicity was dependent on the enzyme concentration, time of incubation and cellular density. The toxic effect of AChE was not related to its catalytic activity, since the anti-cholinesterase drug BW284C51 and heat inactivation were unable to block the effects of the enzyme. When cells were incubated at 4°C, toxicity was completely blocked, in contrast to cells incubated at 37°C. The presence of serum in the culture medium inhibited the toxic effects of AChE. Cytoplasmic shrinkage, condensation and fragmentation of nucleus as well as DNA strand breaks detected with the TUNEL technique indicated that apoptotic cell death is involved in the effect of AChE. Considering that we have previously shown that AChE promotes the assembly of β-amyloid peptide into neurotoxic amyloid fibrils, it is conceivable that the neurotoxicity of AChE shown here may play a role in the neuronal degeneration observed in Alzheimer's disease.

Original languageEnglish
Pages (from-to)247-255
Number of pages9
JournalMolecular Psychiatry
Volume3
Issue number3
DOIs
Publication statusPublished - 1998

Keywords

  • Acetylcholinesterase
  • Alzheimer's disease
  • Neurotoxicity
  • Non-cholinergic action
  • Senile plaques

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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