Search: WFRF:(Ihse Elisabet 1977 ) >
Low molar excess of...
Low molar excess of 4-oxo-2-nonenal and 4-hydroxy-2-nonenal promote oligomerization of alpha-synuclein through different pathways
-
- Almandoz-Gil, Leire (author)
- Uppsala universitet,Geriatrik
-
- Welander, Hedvig (author)
- Uppsala universitet,Geriatrik
-
- Ihse, Elisabet, 1977- (author)
- Uppsala universitet,Geriatrik
-
show more...
-
- Khoonsari, Payam Emami (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
-
- Musunuri, Sravani (author)
- Uppsala universitet,Analytisk kemi
-
- Lendel, Christofer (author)
- KTH,Tillämpad fysikalisk kemi,KTH, Royal Institute of Technology, Sweden
-
- Sigvardson, Jessica (author)
- BioArctic AB, Sweden
-
- Karlsson, Mikael (author)
- Uppsala universitet,Tillämpad materialvetenskap
-
- Ingelsson, Martin (author)
- Uppsala universitet,Geriatrik
-
- Kultima, Kim (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
-
- Bergström, Joakim (author)
- Uppsala universitet,Geriatrik
-
show less...
-
(creator_code:org_t)
- Elsevier BV, 2017
- 2017
- English.
-
In: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 110, s. 421-431
- Related links:
-
https://doi.org/10.1...
-
show more...
-
https://uu.diva-port... (primary) (Raw object)
-
https://uu.diva-port...
-
https://doi.org/10.1...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
https://urn.kb.se/re...
-
show less...
Abstract
Subject headings
Close
- Aggregated alpha-synuclein is the main component of Lewy bodies, intraneuronal inclusions found in brains with Parkinson's disease and dementia with Lewy bodies. A body of evidence implicates oxidative stress in the pathogenesis of these diseases. For example, a large excess (30:1, aldehyde:protein) of the lipid peroxidation end products 4-oxo-2-nonenal (ONE) or 4-hydroxy-2-nonenal (HNE) can induce alpha-synuclein oligomer formation. The objective of the study was to investigate the effect of these reactive aldehydes on alpha-synuclein at a lower molar excess (3:1) at both physiological (7.4) and acidic (5.4) pH. As observed by size-exclusion chromatography, ONE rapidly induced the formation of alpha-synuclein oligomers at both pH values, but the effect was less pronounced under the acidic condition. In contrast, only a small proportion of alpha-synuclein oligomers were formed with low excess HNE-treatment at physiological pH and no oligomers at all under the acidic condition. With prolonged incubation times (up to 96 h), more alpha-synuclein was oligomerized at physiological pH for both ONE and HNE. As determined by Western blot, ONE-oligomers were more SDS-stable and to a higher-degree cross-linked as compared to the HNE-induced oligomers. However, as shown by their greater sensitivity to proteinase K treatment, ONE-oligomers, exhibited a less compact structure than HNE-oligomers. As indicated by mass spectrometry, ONE modified most Lys residues, whereas HNE primarily modified the His50 residue and fewer Lys residues, albeit to a higher degree than ONE. Taken together, our data show that the aldehydes ONE and HNE can modify alpha-synuclein and induce oligomerization, even at low molar excess, but to a higher degree at physiological pH and seemingly through different pathways.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Keyword
- Alpha-synuclein
- Oligomers
- 4-oxo-2-nonenal
- 4-hydroxy-2-nonenal
- Oxidative stress
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Almandoz-Gil, Le ...
-
Welander, Hedvig
-
Ihse, Elisabet, ...
-
Khoonsari, Payam ...
-
Musunuri, Sravan ...
-
Lendel, Christof ...
-
show more...
-
Sigvardson, Jess ...
-
Karlsson, Mikael
-
Ingelsson, Marti ...
-
Kultima, Kim
-
Bergström, Joaki ...
-
show less...
- About the subject
-
- NATURAL SCIENCES
-
NATURAL SCIENCES
-
and Biological Scien ...
-
and Biochemistry and ...
-
- NATURAL SCIENCES
-
NATURAL SCIENCES
-
and Biological Scien ...
- Articles in the publication
-
Free Radical Bio ...
- By the university
-
Uppsala University
-
Royal Institute of Technology