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.
Zheng
Lin
L
Division of Geriatric Medicine, Faculty of Health Sciences, Linköping University, Sweden. linzh@inr.liu.se
Roberg
Karin
K
Jerhammar
Fredrik
F
Marcusson
Jan
J
Terman
Alexei
A
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
D016229:Amyloid beta-Peptides; C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins