Zhao, BL (reprint author), Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100101, Peoples R China.
Recent studies indicate that the deposition of beta-amyloid peptide (A beta) is related to the pathogenesis of Alzheimer disease (AD); however, the underlying mechanism is still not clear. The abnormal interactions of A beta with metal ions such as iron are implicated in the process of A beta deposition and oxidative stress in AD brains. In this study, we observed that A beta increased the levels of iron content and oxidative stress in SH-SY5Y cells overexpressing the Swedish mutant form of human beta-amyloid precursor protein (APPsw) and in Caenorhabditis elegans A beta-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 A beta 1-40 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 A beta-expression had increased iron accumulation. In aggregate, these results demonstrate that A beta accumulation in neuronal cells correlated with neuronal iron homeostasis disruption and probably contributed to the pathogenesis of AD. (C) 2010 Elsevier Inc. All rights reserved.
Wan, L,Nie, GJ,Zhang, J,et al. beta-Amyloid peptide increases levels of iron content and oxidative stress in human cell and Caenorhabditis elegans models of Alzheimer disease[J]. FREE RADICAL BIOLOGY AND MEDICINE,2011,50(1):#REF!.
Wan, L.,Nie, GJ.,Zhang, J.,Luo, YF.,Zhang, P.,...&张智勇.(2011).beta-Amyloid peptide increases levels of iron content and oxidative stress in human cell and Caenorhabditis elegans models of Alzheimer disease.FREE RADICAL BIOLOGY AND MEDICINE,50(1),#REF!.
Wan, L,et al."beta-Amyloid peptide increases levels of iron content and oxidative stress in human cell and Caenorhabditis elegans models of Alzheimer disease".FREE RADICAL BIOLOGY AND MEDICINE 50.1(2011):#REF!.