Oxidative stress induces intracellular accumulation of amyloid β-protein (Aβ) in human neuroblastoma cells
Oxidative stress induces intracellular accumulation of amyloid β-protein (Aβ) in human neuroblastoma cells
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DOI：
10.1021/bi000169p
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发表时间：
2000-06-13
期刊：
影响因子：
2.9
通讯作者：
Ihara, Y
中科院分区：
文献类型：
--
作者：
Misonou, H;Morishima-Kawashima, M;Ihara, Y
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 (A beta) 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 A beta metabolism within the cell. Here, we report that oxidative stress induced by H2O2 (100-250 mu M) caused an increase in the levels of intracellular A beta in human neuroblastoma SH-SY5Y cells. Treatment with 200 mu M H2O2 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 H2O2-treated cells. These results suggest that oxidative stress promotes intracellular accumulation of A beta through enhancing the amyloidogenic pathway.
