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Changes in secondar...
Changes in secondary structure of alpha-synuclein during oligomerization induced by reactive aldehydes
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- Cai, Yixiao (author)
- Uppsala universitet,Tillämpad materialvetenskap
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- Lendel, Christofer (author)
- KTH,Tillämpad fysikalisk kemi
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- Österlund, Lars, 1967- (author)
- Uppsala universitet,Fasta tillståndets fysik
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Kasrayan, Alex (author)
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- Lannfelt, Lars (author)
- Uppsala universitet,Geriatrik
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- Ingelsson, Martin (author)
- Uppsala universitet,Geriatrik
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- Nikolajeff, Fredrik (author)
- Uppsala universitet,Tillämpad materialvetenskap
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- Karlsson, Mikael (author)
- Uppsala universitet,Tillämpad materialvetenskap
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- Bergström, Joakim (author)
- Uppsala universitet,Geriatrik
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(creator_code:org_t)
- Elsevier BV, 2015
- 2015
- English.
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In: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 464:1, s. 336-341
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- The oxidative stress-related reactive aldehydes 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) have been shown to promote formation of alpha-synuclein oligomers in vitro. However, the changes in secondary structure of alpha-synuclein and the kinetics of the oligomerization process are not known and were the focus of this study. Size exclusion chromatography showed that after 1 h of incubation, HNE induced the formation of an oligomeric alpha-synuclein peak with a molecular weight of about similar to 2000 kDa, which coincided with a decreasing similar to 50 kDa monomeric peak. With prolonged incubation (up to 24 h) the oligomeric peak became the dominating molecular species. In contrast, in the presence of ONE, a similar to 2000 oligomeric peak was exclusively observed after 15 min of incubation and this peak remained constant with prolonged incubation. Western blot analysis of HNE-induced alpha-synuclein oligomers showed the presence of monomers (15 kDa), SDS-resistant low molecular (30-160 kDa) and high molecular weight oligomers (>= 260 kDa), indicating that the oligomers consisted of both covalent and non-covalent protein. In contrast, ONE-induced alpha-synuclein oligomers only migrated as covalent cross-linked high molecular-weight material (>= 300 kDa). Both circular dichroism (CD) and Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy showed that the formation of HNE- and ONE-induced oligomers coincided with a spectral change from random coil to beta-sheet. However, ONE-induced alpha-synuclein oligomers exhibited a slightly higher degree of beta-sheet. Taken together, our results indicate that both HNE and ONE induce a change from random coil to beta-sheet structure that coincides with the formation of alpha-synuclein oligomers; albeit through different kinetic pathways depending on the degree of cross-linking. (C) 2015 Elsevier Inc. All rights reserved.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- Alpha-synuclein
- Oligomers
- Aggregation
- Amyloid
- Oxidative stress
- 4-Hydroxy-2-nonenal
- 4-Oxo-2-nonenal
- Parkinson's disease
- Dementia with Lewy bodies
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Cai, Yixiao
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Lendel, Christof ...
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Österlund, Lars, ...
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Kasrayan, Alex
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Lannfelt, Lars
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Ingelsson, Marti ...
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show more...
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Nikolajeff, Fred ...
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Karlsson, Mikael
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Bergström, Joaki ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biophysics
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
- Articles in the publication
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Biochemical and ...
- By the university
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Royal Institute of Technology
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Uppsala University