Oxidative Stress Induces Intracellular Accumulation of Amyloid β-Protein (Aβ) in Human Neuroblastoma Cells
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- 19 May 2000
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 39 (23) , 6951-6959
- https://doi.org/10.1021/bi000169p
Abstract
Several lines of evidence suggest that enhanced oxidative stress is involved in the pathogenesis and/or progression of Alzheimer's disease (AD). Amyloid β-protein (Aβ) that composes senile plaques, a major neuropathological hallmark of AD, is considered to have a causal role in AD. Thus, we have studied the effect of oxidative stress on Aβ metabolism within the cell. Here, we report that oxidative stress induced by H2O2 (100−250 μM) caused an increase in the levels of intracellular Aβ in human neuroblastoma SH-SY5Y cells. Treatment with 200 μM H2O2 caused significant decreases in the protein levels of full-length β-amyloid precursor protein (APP) and its COOH-terminal fragment that is generated by β-cleavage, while the gene expression of APP was not altered under these conditions. A pulse-chase experiment further showed a decrease in the half-life of this amyloidogenic COOH-terminal fragment but not in that of nonamyloidogenic counterpart in the H2O2-treated cells. These results suggest that oxidative stress promotes intracellular accumulation of Aβ through enhancing the amyloidogenic pathway.Keywords
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