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The lipid peroxidat...
The lipid peroxidation products 4-oxo-2-nonenal and 4-hydroxy-2-nonenal promote the formation of α-synuclein oligomers with distinct biochemical, morphological, and functional properties
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- Näsström, Thomas (författare)
- Uppsala universitet,Geriatrik
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- Fagerqvist, Therese (författare)
- Uppsala universitet,Institutionen för folkhälso- och vårdvetenskap
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- Barbu, Mikael (författare)
- Uppsala universitet,Institutionen för folkhälso- och vårdvetenskap
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- Karlsson, Mikael (författare)
- Uppsala universitet,Mikrosystemteknik
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- Nikolajeff, Fredrik (författare)
- Uppsala universitet,Mikrosystemteknik
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- Kasrayan, Alex (författare)
- Bioarctic Neuroscience AB, Stockholm
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- Ekberg, Monica (författare)
- Bioarctic Neuroscience AB, Stockholm
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- Lannfelt, Lars (författare)
- Uppsala universitet,Geriatrik
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- Ingelsson, Martin (författare)
- Uppsala universitet,Geriatrik
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- Bergström, Joakim (författare)
- Uppsala universitet,Geriatrik
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(creator_code:org_t)
- Elsevier BV, 2011
- 2011
- Engelska.
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Ingår i: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 50:3, s. 428-437
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Oxidative stress has been implicated in the etiology of neurodegenerative disorders with alpha-synuclein pathology. Lipid peroxidation products such as 4-oxo-2-nonenal (ONE) and 4-hydroxy-2-nonenal (HNE) can covalently modify and structurally alter proteins. Herein, we have characterized ONE- or HNE-induced alpha-synuclein oligomers. Our results demonstrate that both oligomers are rich in beta-sheet structure and have a molecular weight of about 2000 kDa. Atomic force microscopy analysis revealed that ONE-induced alpha-synuclein oligomers were relatively amorphous, with a diameter of 40-80 nm and a height of 4-8 nm. In contrast, the HNE-induced alpha-synuclein oligomers had a protofibril-like morphology with a width of 100-200 nm and a height of 2-4 nm. Furthermore, neither oligomer type polymerized into amyloid-like fibrils despite prolonged incubation. Although more SDS and urea stable, because of a higher degree of cross-linking, ONE-induced alpha-synuclein oligomers were less compact and more sensitive to proteinase K treatment. Finally, both ONE- and HNE-induced alpha-synuclein oligomers were cytotoxic when added exogenously to a neuroblastoma cell line, but HNE-induced alpha-synuclein oligomers were taken up by the cells to a significantly higher degree. Despite nearly identical chemical structures, ONE and HNE induce the formation of off-pathway alpha-synuclein oligomers with distinct biochemical, morphological, and functional properties.
Ämnesord
- TEKNIK OCH TEKNOLOGIER -- Materialteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Materials Engineering (hsv//eng)
Nyckelord
- alpha-Synuclein
- Oligomers
- Lewy bodies
- Lipid peroxidation
- 4-Oxo-2-nonenal
- Oxidative stress
- 4-Hydroxy-2-nonenal
- Free radicals
- MEDICINE
- MEDICIN
- Teknisk fysik med inriktning mot mikrosystemteknik
- Engineering Science with specialization in Microsystems Technology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Näsström, Thomas
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Fagerqvist, Ther ...
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Barbu, Mikael
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Karlsson, Mikael
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Nikolajeff, Fred ...
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Kasrayan, Alex
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visa fler...
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Ekberg, Monica
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Lannfelt, Lars
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Ingelsson, Marti ...
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Bergström, Joaki ...
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visa färre...
- Om ämnet
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- TEKNIK OCH TEKNOLOGIER
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TEKNIK OCH TEKNO ...
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och Materialteknik
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Free Radical Bio ...
- Av lärosätet
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Uppsala universitet