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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1989-2-22
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pubmed:abstractText |
The present studies were carried out to investigate the comparative roles of protein cross-linking and alteration in protein phosphorylation in the accumulation of neurofilaments due to aliphatic hexacarbons. In these studies, rats were given 2,5-hexanedione (0, 0.1, 0.25 and 1.0%) for 70 days in their drinking water. In a separate study of in vitro protein phosphorylation rats were given 1% 2,5-hexanedione for 14 days in their drinking water. Spinal cord neurofilaments were isolated and analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblotting using anti-neurofilament antibodies, radioimmunoassays (RIAs) of phosphorylated epitopes on neurofilament proteins and protein phosphorylation. Protein cross-linking of neurofilaments was found in all animals treated with 2,5-hexanedione including the lowest dose (0.1%) which did not produce clinical signs of intoxication. Protein phosphorylation of neurofilament proteins, as well as MAP-2 was significantly decreased upon treatment. Protein staining revealed a decreased amount of neurofilament protein and immunoblotting demonstrated neurofilament protein cross-linking in these animals. Protein staining of glial fibrillary acidic protein (GFAP) was unaltered by this treatment. RIAs of phosphorylated and non-phosphorylated epitopes of neurofilament proteins indicated that in vivo phosphorylation of these proteins was also decreased. Two-dimensional gel electrophoresis indicated a shift of the neurofilament proteins to a basic pI, indicating a dephosphorylation of neurofilament proteins. Cross-linked neurofilament proteins also exhibited a pI which was more basic than any of the individual neurofilament proteins. This report demonstrates differential effects of 2,5-hexanedione on neurofilament proteins and indicates that several mechanisms may be responsible for their accumulation.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2,5-hexanedione,
http://linkedlifedata.com/resource/pubmed/chemical/Hexanones,
http://linkedlifedata.com/resource/pubmed/chemical/Intermediate Filament Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ketones,
http://linkedlifedata.com/resource/pubmed/chemical/Neurofilament Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neurotoxins
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-8993
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
458
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
123-31
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:3145093-Animals,
pubmed-meshheading:3145093-Dose-Response Relationship, Drug,
pubmed-meshheading:3145093-Hexanones,
pubmed-meshheading:3145093-Intermediate Filament Proteins,
pubmed-meshheading:3145093-Intermediate Filaments,
pubmed-meshheading:3145093-Ketones,
pubmed-meshheading:3145093-Male,
pubmed-meshheading:3145093-Molecular Weight,
pubmed-meshheading:3145093-Neurofilament Proteins,
pubmed-meshheading:3145093-Neurotoxins,
pubmed-meshheading:3145093-Phosphorylation,
pubmed-meshheading:3145093-Rats,
pubmed-meshheading:3145093-Rats, Inbred Strains,
pubmed-meshheading:3145093-Reference Values,
pubmed-meshheading:3145093-Spinal Cord
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pubmed:year |
1988
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pubmed:articleTitle |
Evidence for multiple mechanisms responsible for 2,5-hexanedione-induced neuropathy.
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pubmed:affiliation |
Department of Pharmacology, Duke University Medical Center, NC 27710.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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