| β-Amyloid peptide increases levels of iron content and oxidative stress in human cell and Caenorhabditis elegans models of Alzheimer disease. | |
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MedLine Citation:
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PMID: 21034809 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Recent studies indicate that the deposition of β-amyloid peptide (Aβ) is related to the pathogenesis of Alzheimer disease (AD); however, the underlying mechanism is still not clear. The abnormal interactions of Aβ with metal ions such as iron are implicated in the process of Aβ deposition and oxidative stress in AD brains. In this study, we observed that Aβ increased the levels of iron content and oxidative stress in SH-SY5Y cells overexpressing the Swedish mutant form of human β-amyloid precursor protein (APPsw) and in Caenorhabditis elegans Aβ-expressing strain CL2006. Intracellular iron and calcium levels and reactive oxygen species and nitric oxide generation significantly increased in APPsw cells compared to control cells. The activity of superoxide dismutase and the antioxidant levels of APPsw cells were significantly lower than those of control cells. Moreover, iron treatment decreased cell viability and mitochondrial membrane potential and aggravated oxidative stress damage as well as the release of Aβ1-40 from the APPsw cells. The iron homeostasis disruption in APPsw cells is very probably associated with elevated expression of the iron transporter divalent metal transporter 1, but not transferrin receptor. Furthermore, the C. elegans with Aβ-expression had increased iron accumulation. In aggregate, these results demonstrate that Aβ accumulation in neuronal cells correlated with neuronal iron homeostasis disruption and probably contributed to the pathogenesis of AD. |
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Authors:
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Li Wan; Guangjun Nie; Jie Zhang; Yunfeng Luo; Peng Zhang; Zhiyong Zhang; Baolu Zhao |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-26 |
Journal Detail:
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Title: Free radical biology & medicine Volume: 50 ISSN: 1873-4596 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-03 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: United States |
Other Details:
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Languages: eng Pagination: 122-9 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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