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| Content Provider | PubMed Central |
|---|---|
| Author | Zheng, Lin Terman, Alexei Hallbeck, Martin Dehvari, Nodi Cowburn, Richard F. Benedikz, Eirikur Katarina, Kågedal Angel, Cedazo-minguez Jan, Marcusson |
| Copyright Year | 2011 |
| Abstract | Increasing evidence suggests the toxicity of intracellular amyloid β-protein (Aβ) to neurons, as well as the involvement of oxidative stress in Alzheimer disease (AD). Here we show that normobaric hyperoxia (exposure of cells to 40% oxygen for five days), and consequent activation of macroautophagy and accumulation of Aβ within lysosomes, induced apoptosis in differentiated SH-SY5Y neuroblastoma cells. Cells under hyperoxia showed: (1) increased numbers of autophagic vacuoles that contained amyloid precursor protein (APP) as well as Aβ monomers and oligomers, (2) increased reactive oxygen species production, and (3) enhanced apoptosis. Oxidant-induced apoptosis positively correlated with cellular Aβ production, being the highest in cells that were stably transfected with APP Swedish KM670/671NL double mutation. Inhibition of γ-secretase, prior and/or in parallel to hyperoxia, suggested that the increase of lysosomal Aβ resulted mainly from its autophagic uptake, but also from APP processing within autophagic vacuoles. The oxidative stress-mediated effects were prevented by macroautophagy inhibition using 3-methyladenine or ATG5 downregulation. Our results suggest that upregulation of macroautophagy and resulting lysosomal Aβ accumulation are essential for oxidant-induced apoptosis in cultured neuroblastoma cells and provide additional support for the interactive role of oxidative stress and the lysosomal system in AD-related neurodegeneration. |
| Related Links | http://dx.doi.org/10.4161/auto.7.12.18051 |
| Starting Page | 1528 |
| File Format | |
| ISSN | 15548635 |
| e-ISSN | 15548635 |
| Journal | Autophagy |
| Issue Number | 12 |
| Volume Number | 7 |
| Language | English |
| Publisher | Landes Bioscience |
| Publisher Date | 2011-12-01 |
| Access Restriction | Open |
| Rights Holder | Landes Bioscience |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
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