Overexpression of Human Wild-Type Amyloid-β Protein Precursor Decreases the Iron Content and Increases the Oxidative Stress of Neuroblastoma SH-SY5Y Cells
Affiliations: [a] >State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China | [b] Graduate School, Chinese Academy of Sciences, Beijing, China | [c] CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing, China | [d] Center for Neurodegenerative Disease and Aging Research, Medical College, Xiamen University, Xiamen, Fujian, China
Correspondence:
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Correspondence to: Baolu Zhao, State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, 100101 Beijing, China. Fax: +86 10 64871293; E-mail: [email protected].
Abstract: The accumulation of amyloid-β protein precursor (AβPP) is related to the pathogenesis of Alzheimer's disease (AD); however, the underlying mechanism is still unclear. The abnormal interactions of AβPP with metal ions such as iron are implicated in the process of oxidative stress in AD brains. In this study, we found that the overexpression of wild-type human AβPP695 decreased the iron content and increased the oxidative stress in neuroblastoma SH-SY5Y cells. The catalase activity of stably transfected cells overexpressing wild-type AβPP695 (AβPP cells) was significantly lower than that of the control cells. Intracellular reactive oxygen species (ROS) generation and calcium levels significantly increased in AβPP cells compared to control cells. The mitochondrial membrane potential of AβPP cells was significantly lower than that of the control cells. Moreover, iron treatment decreased ROS and calcium levels and increased cell viability of AβPP cells. The iron deficiency in AβPP cells may contribute to the pathogenesis of AD.
Keywords: Alzheimer's disease, amyloid-β protein precursor, iron deficiency, oxidative stress
