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- W1968643079 abstract "Increasing evidence suggests the toxicity of intracellular amyloid beta-protein (Ab) to neurons and the involvement of lysosomes in this process in Alzheimer's disease (AD). We have previously shown that oxidative stress enhances autophagy and leads to intralysosomal accumulation of Ab in cultured neuroblastoma cells. Furthermore, we have found that oxidative stress can induce neuronal death through autophagy of Ab and consequent lysosomal membrane permeabilization in cultured HEK293 cells. To further investigate the involvement of autophagy in Ab cytotocicity, we compared the effects of hyperoxia (exposure of cells to 40% ambient oxygen for five days) in retinoic acid differentiated neuroblastoma SH-SY5Y (neuronal-like) cells that were stably transfected with APPwt, or APPswe or vector only. Autophagy was detected by immunofluorecsence microscopy (immunoreactivity to LC3 and LAMP-2), western blotting (using antibodies to LC3) and electron microscopy. Reactive oxygen species (ROS) were assessed by flow cytometry (DCFH oxidation method). Hyperoxia-exposed neuroblastoma cells showed an increased content of Ab-containing lysosomes/autophagic vacuoles, enhanced apoptosis, as well as increased ROS production as compared to cells cultured at normoxic conditions. This effect of hyperoxia was more pronounced in Ab-overproducing cells (vector<APPwt<APPswe). Furthermore, an inhibitor of macroautophagy 3-methyladenine (3MA), prevented these effects of hyperoxia in all neuroblastoma cell lines used in the study. These results suggest that autophagy of Ab is crucial for oxidant-induced apoptosis in cultured neuroblastoma cells. They may help better understanding of the mechanisms behind neuronal loss in AD and suggest new therapeutic approaches for its management." @default.
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- W1968643079 date "2010-07-01" @default.
- W1968643079 modified "2023-10-02" @default.
- W1968643079 title "P4‐042: The Role of Oxidative Stress and Autophagy in Amyloid Beta‐protein Toxicity to Cultured Neuroblastoma Cells" @default.
- W1968643079 doi "https://doi.org/10.1016/j.jalz.2010.08.102" @default.
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