Oxidative Stress Induces Intralysosomal Accumulation of Alzheimer Amyloid Beta-protein in Cultured Neuroblastoma Cells

Oxidative stress is considered important for the pathogenesis of Alzheimer's disease (AD), which is characterized by the formation of extracellular senile plaques, mainly composed of amyloid beta-protein (Abeta). Abeta also accumulates within AD neurons and is believed to exert cellular toxicity through lysosomal labilization. We report that the exposure of human neuroblastoma cells to hyperoxia (40% vs. 8% ambient oxygen) induced the accumulation of large (over 1 microM) Abeta-containing lysosomes, which were not typical of control cells, showing a distinct localization of Abeta and lysosomal markers. An inhibitor of autophagy, 3-methyladenine, suppressed the effect of hyperoxia. The results suggest a link between the involvement of oxidative stress and lysosomes in AD.