| Macroautophagy-generated increase of lysosomal amyloid β-protein mediates oxidant-induced apoptosis of cultured neuroblastoma cells. | |
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MedLine Citation:
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PMID: 22108004 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 aditional support for the interactive role of oxidative stress and the lysosomal system in AD-related neurodegeneration. |
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Authors:
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Lin Zheng; Alexei Terman; Martin Hallbeck; Nodi Dehvari; Richard F Cowburn; Eirikur Benedikz; Katarina Kågedal; Angel Cedazo-Minguez; Jan Marcusson |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-01 |
Journal Detail:
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Title: Autophagy Volume: 7 ISSN: 1554-8635 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-11-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101265188 Medline TA: Autophagy Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Geriatric Medicine; Department of Clinical and Experimental Medicine; IKE; Faculty of Health Sciences; Linköping University; Linköping, Sweden. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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