Abstract
Amyloid β (Aβ) neurotoxicity is believed to play a critical role in the pathogenesis of Alzheimer's disease (AD) mainly because of its deposition in AD brain and its neuronal toxicity. However, there have been discrepancies in Aβ-induced cytotoxicity studies, depending on the assay methods. Comparative analysis of Aβ42-induced in vitro cytotoxicity might be useful to elucidate the etiological role of Aβ in the pathogenesis of AD. In this study, MTT, CCK-8, calcein-AM/EthD-1 assays as well as thorough microscopic examinations were comparatively performed after Aβ42 treatment in a neuronal precursor cells (NT2) and a somatic cells (EcR293). Extensive formation of vacuoles was observed at the very early stage of Aβ42 treatment in both cells. Early observation of Aβ42 toxicity as seen in vacuole formation was also shown in MTT assay, but not in CCK-8 and calcein-AM/EthD-1 assays. In addition, Aβ42 treatment dramatically accelerated MTT formazan exocytosis, implying its effect on the extensive formation of cytoplasmic vacuoles. Aβ42 seems to cause indirect inhibition on the intracellular MTT reduction as well as vacuole formation and exocytosis enhancement. Following the acute cellular dysfunction induced by Aβ42, the prolonged treatment of micromolar concentration of Aβ42 resulted in slight inhibition on redox and esterase activity. The early Aβ42-induced vacuolated morphology and later chronic cytotoxic effect in neuronal cell might be linked to the chronic neurodegeneration caused by the accumulation of Aβ42 in AD patients' brain.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Liu, ML., Hong, ST. Early phase of amyloid β42-induced cytotoxicity in neuronal cells is associated with vacuole formation and enhancement of exocytosis. Exp Mol Med 37, 559–566 (2005). https://doi.org/10.1038/emm.2005.69
Published:
Issue Date:
DOI: https://doi.org/10.1038/emm.2005.69
Keywords
This article is cited by
-
Molecularly imprinted sensor based on poly-o-phenylenediamine-hydroquinone polymer for β-amyloid-42 detection
Analytical and Bioanalytical Chemistry (2023)
-
BASP1 – an Axon Terminal Protein Forming Amyloid-Like Oligomers
Neuroscience and Behavioral Physiology (2015)
-
Pro-inflammatory interleukin-18 increases Alzheimer’s disease-associated amyloid-β production in human neuron-like cells
Journal of Neuroinflammation (2012)
-
Ursolic acid-induced apoptosis in K562 cells involving upregulation of PTEN gene expression and inactivation of the PI3K/Akt pathway
Archives of Pharmacal Research (2012)
-
Pre-aggregated Aβ1–42 peptide increases tau aggregation and hyperphosphorylation after short-term application
Molecular and Cellular Biochemistry (2011)