Source:http://linkedlifedata.com/resource/pubmed/id/10860544
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2000-7-17
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| pubmed:abstractText |
alpha-Synuclein is a component of abnormal protein depositions of Lewy bodies and senile plaques found in Parkinson's and Alzheimer's diseases, respectively. By using chemical coupling reagents such as dicyclohexylcarbodiimide or N-(ethoxycarbonyl)-2-ethoxy-1, 2-dihydroquinoline, the protein was shown to experience self-oligomerization in the presence of either copper(II) or Abeta25-35. The oligomers which appeared as a ladder on a 10-20% Tricine/SDS-PAGE have been suggested to participate in the formation of protein aggregations by possibly providing a nucleation center. Since oxidatively modified protein could increase its own tendency toward protein aggregation, metal-catalyzed oxidation of alpha-synuclein has been examined with copper(II) and hydrogen peroxide in the absence of the coupling reagent. Intriguingly, the protein was also self-oligomerized into an SDS-resistant ladder on the gel. This biochemically specific copper-mediated oxidative oligomerization was shown to be dependent upon the acidic C-terminus of alpha-synuclein because the C-terminally truncated proteins such as alpha-syn114 and alpha-syn97 were not affected by the metal and hydrogen peroxide. More importantly, the oxidative oligomerization was synergistically enhanced by the presence of Abeta25-35, indicating that the peptide interaction with alpha-synuclein facilitated the copper(II) binding to the acidic C-terminus and subsequent oxidative crosslinking. It has been, therefore, suggested that abnormalities in copper and H(2)O(2) homeostasis and certain pathological factors functionally similar to the Abeta25-35 could play critical roles in the metal-catalyzed oxidative oligomerization of alpha-synuclein, which may lead to possible protein aggregation and neurodegenerations.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alkylating Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Chlorides,
http://linkedlifedata.com/resource/pubmed/chemical/Copper,
http://linkedlifedata.com/resource/pubmed/chemical/Dicyclohexylcarbodiimide,
http://linkedlifedata.com/resource/pubmed/chemical/EEDQ,
http://linkedlifedata.com/resource/pubmed/chemical/Ferric Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/Metals,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Quinolines,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SNCA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Synucleins,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-Synuclein,
http://linkedlifedata.com/resource/pubmed/chemical/cupric chloride,
http://linkedlifedata.com/resource/pubmed/chemical/ferric chloride
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
0003-9861
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 2000 Academic Press.
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| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
378
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
269-77
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:10860544-Alkylating Agents,
pubmed-meshheading:10860544-Alzheimer Disease,
pubmed-meshheading:10860544-Catalysis,
pubmed-meshheading:10860544-Chlorides,
pubmed-meshheading:10860544-Copper,
pubmed-meshheading:10860544-Dicyclohexylcarbodiimide,
pubmed-meshheading:10860544-Dose-Response Relationship, Drug,
pubmed-meshheading:10860544-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:10860544-Ferric Compounds,
pubmed-meshheading:10860544-Humans,
pubmed-meshheading:10860544-Hydrogen Peroxide,
pubmed-meshheading:10860544-Metals,
pubmed-meshheading:10860544-Nerve Tissue Proteins,
pubmed-meshheading:10860544-Oxidation-Reduction,
pubmed-meshheading:10860544-Quinolines,
pubmed-meshheading:10860544-Recombinant Proteins,
pubmed-meshheading:10860544-Spectrometry, Fluorescence,
pubmed-meshheading:10860544-Synucleins,
pubmed-meshheading:10860544-Time Factors,
pubmed-meshheading:10860544-alpha-Synuclein
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| pubmed:year |
2000
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| pubmed:articleTitle |
Metal-catalyzed oxidation of alpha-synuclein in the presence of Copper(II) and hydrogen peroxide.
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| pubmed:affiliation |
Department of Biochemistry, College of Medicine, Inha University, 253 Yonghyun-Dong, Inchon, 402-751, Korea. sraik@dragon.inha.ac.kr
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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