Overexpression of Human Wild-Type Amyloid-β Protein Precursor Decreases the Iron Content and Increases the Oxidative Stress of Neuroblastoma SH-SY5Y Cells

The accumulation of amyloid-beta protein precursor (A beta PP) is related to the pathogenesis of Alzheimer's disease (AD); however, the underlying mechanism is still unclear. The abnormal interactions of A beta PP 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 A beta PP695 decreased the iron content and increased the oxidative stress in neuroblastoma SH-SY5Y cells. The catalase activity of stably transfected cells overexpressing wild-type A beta PP695 (A beta PP cells) was significantly lower than that of the control cells. Intracellular reactive oxygen species (ROS) generation and calcium levels significantly increased in A beta PP cells compared to control cells. The mitochondrial membrane potential of A beta PP cells was significantly lower than that of the control cells. Moreover, iron treatment decreased ROS and calcium levels and increased cell viability of A beta PP cells. The iron deficiency in A beta PP cells may contribute to the pathogenesis of AD.