Cited by 304Alzheimer's disease research and treatmentsRedox biology and oxidative stressDementia and Cognitive Impairment Research

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Oxidative Stress Induces Intracellular Accumulation of Amyloid β-Protein (Aβ) in Human Neuroblastoma Cells

Misonou, Hiroaki, Morishima-Kawashima, Maho, Ihara, Yasuo·2000·Biochemistry

DOI 10.1021/bi000169p

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Abstract

Several lines of evidence suggest that enhanced oxidative stress is involved in the pathogenesis and/or progression of Alzheimer's disease (AD). Amyloid beta-protein (Abeta) 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 Abeta metabolism within the cell. Here, we report that oxidative stress induced by H(2)O(2) (100-250 microM) caused an increase in the levels of intracellular Abeta in human neuroblastoma SH-SY5Y cells. Treatment with 200 microM H(2)O(2) caused significant decreases in the protein levels of full-length beta-amyloid precursor protein (APP) and its COOH-terminal fragment that is generated by beta-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 H(2)O(2)-treated cells. These results suggest that oxidative stress promotes intracellular accumulation of Abeta through enhancing the amyloidogenic pathway.

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Abbreviations AD, Alzheimer's disease

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Authors: Misonou, H., Morishima-Kawashima, M., & Ihara, Y.
Affiliations: Japan Science and Technology Agency (JP)
Department of Neuropathology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, and Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Kawaguchi, Saitama 332-0012, Japan
Corresponding author: Ihara, Yasuo
ORCID: Misonou, Hiroaki
Ihara, Yasuo
Venue: Biochemistry
Publisher: American Chemical Society (ACS)
Published: 2000-05-19
Volume: 39
Issue: 23
Pages: 6951-6959
ISSN: 0006-2960 (ISSN-L)
1520-4995
DOI: 10.1021/bi000169p
OpenAlex: W2048360633
Cited by: 304
References: 19
Citations by year: 2026: 4 · 2025: 3 · 2024: 11 · 2023: 12 · 2022: 6 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 19 · 2017: 14 · 2016: 12 · 2015: 10 · 2014: 13 · 2013: 8 · 2012: 15
FWCI: 6.80
Type: journal article
Language: en
Open access: closed
Locations: Biochemistry (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: oxidative stress, amyloid-beta, Alzheimer's disease, hydrogen peroxide, amyloid precursor protein, APP cleavage, amyloidogenic pathway, intracellular accumulation, SH-SY5Y cells, protein half-life, amyloid plaques
MeSH terms: Alzheimer Disease, Animals, Antioxidants, Cell Survival, Chromans, Dimethyl Sulfoxide, Cricetinae, Humans, Hydrogen Peroxide, Neuroblastoma, Peptide Fragments, Phosphatidylserines, RNA, Messenger, Tetrazolium Salts, Thiazoles, Transfection, Tumor Cells, Cultured, Amyloid beta-Peptides, CHO Cells, Amyloid beta-Protein Precursor, Apoptosis, Oxidative Stress

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Oxidative Stress Induces Intracellular Accumulation of Amyloid β-Protein (Aβ) in Human Neuroblastoma Cells

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