title: Oxidative stress induces intralysosomal accumulation of Alzheimer amyloid beta-protein in cultured neuroblastoma cells.
abstract: 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.
authors.affiliation: Division of Geriatric Medicine, Faculty of Health Sciences, Linköping University, Sweden. linzh@inr.liu.se
authors.forename: Lin
authors.initials: L
authors.lastname: Zheng
authors.forename: Karin
authors.initials: K
authors.lastname: Roberg
authors.forename: Fredrik
authors.initials: F
authors.lastname: Jerhammar
authors.forename: Jan
authors.initials: J
authors.lastname: Marcusson
authors.forename: Alexei
authors.initials: A
authors.lastname: Terman
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000378:metabolism / Q000648:ultrastructure; D008247:Lysosomes / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D018384:Oxidative Stress; D014407:Tumor Cells, Cultured
chemical_list: D016229:Amyloid beta-Peptides; C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins