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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2006-4-5
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pubmed:abstractText |
Accumulation of misfolded Cu/Zn superoxide dismutase (SOD1) occurs in patients with a subgroup of familial amyotrophic lateral sclerosis (fALS). To identify the conversion of SOD1 from a normally soluble form to insoluble aggregates, we investigated the change of SOD1 solubility with aging in fALS-linked H46R SOD1 transgenic mice. Mutant SOD1 specifically altered to insoluble forms, which were sequentially separated into Triton X-100-insoluble/sodium dodecyl sulfate (SDS)-soluble and SDS-insoluble/formic acid-soluble species. In spinal cords, the levels of SDS-dissociable soluble SOD1 monomers and SDS-stable soluble dimers were significantly elevated before motor dysfunction onset. In COS-7 cells expressing H46R SOD1, treatment with proteasome inhibitors recapitulated the alteration of SOD1 solubility in transgenic mice. In contrast, overexpression of Hsp70 reduced accumulation of mutant-specific insoluble SOD1. SDS-soluble low molecular weight species of H46R SOD1 may appear as early misfolded intermediates when their concentration exceeds the capacity of the proteasome and molecular chaperones.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0006-291X
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pubmed:author |
pubmed-author:AokiMasashiM,
pubmed-author:ArawakaShigekiS,
pubmed-author:ChanPak HPH,
pubmed-author:ItoyamaYasutoY,
pubmed-author:KatoMasaakiM,
pubmed-author:KatoTakeoT,
pubmed-author:KawanamiToruT,
pubmed-author:KoyamaShingoS,
pubmed-author:KuritaKeijiK,
pubmed-author:NagaiMakikoM,
pubmed-author:RenChang-HongCH,
pubmed-author:SobueGenG,
pubmed-author:WadaManabuM
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pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
343
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
719-30
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16563356-Age Factors,
pubmed-meshheading:16563356-Aging,
pubmed-meshheading:16563356-Amyotrophic Lateral Sclerosis,
pubmed-meshheading:16563356-Animals,
pubmed-meshheading:16563356-COS Cells,
pubmed-meshheading:16563356-Cercopithecus aethiops,
pubmed-meshheading:16563356-Disease Progression,
pubmed-meshheading:16563356-HSP40 Heat-Shock Proteins,
pubmed-meshheading:16563356-HSP70 Heat-Shock Proteins,
pubmed-meshheading:16563356-Humans,
pubmed-meshheading:16563356-Mice,
pubmed-meshheading:16563356-Mice, Transgenic,
pubmed-meshheading:16563356-Mutation,
pubmed-meshheading:16563356-Proteasome Endopeptidase Complex,
pubmed-meshheading:16563356-Protein Folding,
pubmed-meshheading:16563356-Sodium Dodecyl Sulfate,
pubmed-meshheading:16563356-Solubility,
pubmed-meshheading:16563356-Superoxide Dismutase
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pubmed:year |
2006
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pubmed:articleTitle |
Alteration of familial ALS-linked mutant SOD1 solubility with disease progression: its modulation by the proteasome and Hsp70.
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pubmed:affiliation |
Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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