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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
2003-7-4
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pubmed:abstractText |
Heat shock protein 70 (Hsp70) protects cultured motor neurons from the toxic effects of mutations in Cu/Zn-superoxide dismutase (SOD-1), which is responsible for a familial form of the disease, amyotrophic lateral sclerosis (ALS). Here, the endogenous heat shock response of motor neurons was investigated to determine whether a high threshold for activating this protective mechanism contributes to their vulnerability to stresses associated with ALS. When heat shocked, cultured motor neurons failed to express Hsp70 or transactivate a green fluorescent protein reporter gene driven by the Hsp70 promoter, although Hsp70 was induced in glial cells. No increase in Hsp70 occurred in motor neurons after exposure to excitotoxic glutamate or expression of mutant SOD-1 with a glycine--> alanine substitution at residue 93 (G93A), nor was Hsp70 increased in spinal cords of G93A SOD-1 transgenic mice or sporadic or familial ALS patients. In contrast, strong Hsp70 induction occurred in motor neurons with expression of a constitutively active form of heat shock transcription factor (HSF)-1 or when proteasome activity was sufficiently inhibited to induce accumulation of an alternative transcription factor HSF2. These results indicate that the high threshold for induction of the stress response in motor neurons stems from an impaired ability to activate the main heat shock-stress sensor, HSF1.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/HSF2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/HSP70 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/SOD1 G93A protein,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/heat shock transcription factor
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1529-2401
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
2
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5789-98
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12843283-Amyotrophic Lateral Sclerosis,
pubmed-meshheading:12843283-Animals,
pubmed-meshheading:12843283-Cells, Cultured,
pubmed-meshheading:12843283-Cysteine Endopeptidases,
pubmed-meshheading:12843283-DNA-Binding Proteins,
pubmed-meshheading:12843283-Disease Models, Animal,
pubmed-meshheading:12843283-Enzyme Inhibitors,
pubmed-meshheading:12843283-Gene Expression Regulation,
pubmed-meshheading:12843283-Genes, Reporter,
pubmed-meshheading:12843283-Glutamic Acid,
pubmed-meshheading:12843283-HSP70 Heat-Shock Proteins,
pubmed-meshheading:12843283-Heat-Shock Proteins,
pubmed-meshheading:12843283-Heat-Shock Response,
pubmed-meshheading:12843283-Hot Temperature,
pubmed-meshheading:12843283-Humans,
pubmed-meshheading:12843283-Mice,
pubmed-meshheading:12843283-Mice, Transgenic,
pubmed-meshheading:12843283-Motor Neurons,
pubmed-meshheading:12843283-Multienzyme Complexes,
pubmed-meshheading:12843283-Promoter Regions, Genetic,
pubmed-meshheading:12843283-Proteasome Endopeptidase Complex,
pubmed-meshheading:12843283-Spinal Cord,
pubmed-meshheading:12843283-Superoxide Dismutase,
pubmed-meshheading:12843283-Transcription Factors
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pubmed:year |
2003
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pubmed:articleTitle |
High threshold for induction of the stress response in motor neurons is associated with failure to activate HSF1.
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pubmed:affiliation |
Montreal Neurological Institute and Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H3A 2B4.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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