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Macroautophagy-gene...
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Zheng, LinLinköpings universitet,Geriatrik,Hälsouniversitetet
(författare)
Macroautophagy-generated increase of lysosomal amyloid β-protein mediates oxidant-induced apoptosis of cultured neuroblastoma cells
- Artikel/kapitelEngelska2011
Förlag, utgivningsår, omfång ...
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2014-10-28
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Landes Bioscience,2011
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:liu-72778
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-72778URI
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https://doi.org/10.4161/auto.7.12.18051DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:123745461URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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Funding agencies|Gustav V and Queen Victoria Foundation||County Council of Ostergotland||Stiftelsen Olle Engkvist Byggmastare||Stifielsen for Gamla Tjanarinnor||Gunoch Bertil Stohnes Stiftelse||Lions forskningsfond||Svenska Lundbeckstiftelsen||Karolinska Institute Fund for Geriatric Research||Alice och Knut Wallenberg Stiftelse||Swedish Alzheimer Foundation||Swedish Brain Power||
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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.
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Terman, AlexiKarolinska Institutet,Karolinska University Hospital, Stockholm
(författare)
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Hallbeck, MartinÖstergötlands Läns Landsting,Linköpings universitet,Experimentell patologi,Hälsouniversitetet,Klinisk patologi och klinisk genetik(Swepub:liu)marha90
(författare)
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Dehvari, NodiKarolinska Institutet, Stockholm
(författare)
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Cowburn, Richard F.Karolinska Institutet,AstraZeneca, Södertälje
(författare)
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Benedikz, EirikurKarolinska Institutet
(författare)
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Kågedal, KatarinaLinköpings universitet,Experimentell patologi,Hälsouniversitetet(Swepub:liu)katka10
(författare)
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Cedazo-Minguez, AngelKarolinska Institutet
(författare)
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Marcusson, JanÖstergötlands Läns Landsting,Linköpings universitet,Geriatrik,Hälsouniversitetet,Geriatriska kliniken(Swepub:liu)janma25
(författare)
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Linköpings universitetGeriatrik
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Autophagy: Landes Bioscience7:12, s. 1528-15451554-86271554-8635
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