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Amyloid‐like aggregates of neuronal tau are induced by formaldehyde exposure and promote apoptosis of neuronal cells
Author(s) -
He Rong Qiao,
Nie Chun Lai,
Wang Xing Sheng,
liu Ying,
Perrett Sarah
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a954-a
Subject(s) - congo red , thioflavin , chemistry , propidium iodide , amyloid (mycology) , apoptosis , senile plaques , tau protein , annexin , neurotoxicity , biochemistry , microbiology and biotechnology , programmed cell death , biology , alzheimer's disease , pathology , toxicity , medicine , inorganic chemistry , disease , organic chemistry , adsorption
The microtubule associated protein tau is the principle component of neurofibrillar tangles, which are a characteristic marker in the pathology of Alzheimer's Disease; similar lesions are also observed after chronic alcohol abuse. Formaldehyde is a common environmental contaminant and is also a metabolite of methanol. Here we investigate the effect of environmental concentrations of formaldehyde on protein misfolding and aggregation. We found that unlike the typical globular protein BSA, the natively‐unfolded structure of human neuronal tau was induced to misfold and aggregate in the presence of 0.01% formaldehyde, leading to formation of amyloid‐like deposits that appeared as densely staining granules by electron microscopy, and bound the amyloid‐specific dyes thioflavin T and Congo Red. After removal of the formaldehyde, the amyloid‐like aggregates of tau were found to induce apoptosis in the neurotypic cell line SY5Y and in rat hippocampal cells, as observed by Hoechst 33258 staining, assay of caspase‐3 activity, and flow cytometry using Annexin V and Propidium Iodide staining. Control cells incubated with formaldehyde alone, or with tau aggregates formed in the presence of acetaldehyde, formic acid or in the absence of additives (and which did not show appreciable binding of thioflavin T or Congo Red), did not show signs of apoptosis. Further experiments showed that Congo Red and olomoucine (a Cdk inhibitor) specifically attenuated the caspase‐3 activity induced by amyloid‐like deposits of tau. The results suggest that environmental concentrations of formaldehyde may play a role in induction of tauopathies and suggest a role of apoptosis and cyclin dependent kinases in the pathology of these disorders.