Linked Life Data

10942430

Source:http://linkedlifedata.com/resource/pubmed/id/10942430

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2000-10-12
pubmed:abstractText
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by polyglutamine expansion in the disease protein, huntingtin. In HD patients and transgenic mice, the affected neurons form characteristic ubiquitin-positive nuclear inclusions (NIs). We have established ecdysone-inducible stable mouse Neuro2a cell lines that express truncated N-terminal huntingtin (tNhtt) with different polyglutamine lengths which form both cytoplasmic and nuclear aggregates in a polyglutamine length- and inducer dose-dependent manner. Here we demonstrate that newly synthesized polyglutamine-expanded truncated huntingtin interacts with members of Hsp40 and Hsp70 families of chaperones in a polyglutamine length-dependent manner. Of these interacting chaperones, only Hdj-2 and Hsc70 frequently (Hdj-2 > Hsc70) co-localize with both the aggregates in the cellular model and with the NIs in the brains of HD exon 1 transgenic mice. However, Hdj-2 and Hsc70 do not co-localize with cytoplasmic aggregates in the brains of transgenic mice despite these chaperones being primarily localized in the cytoplasmic compartment. This strongly suggests that the chaperone interaction and their redistribution to the aggregates are two completely different phenomena of the cellular unfolded protein response. This unfolded protein response is also evident from the dramatic induction of Hsp70 on expression of polyglutamine-expanded protein in the cellular model. Transient overexpression of either Hdj-1 or Hsc70 suppresses the aggregate formation; however, suppression efficiency is much higher in Hdj-1 compared with Hsc70. Overexpression of Hdj-1 and Hsc70 is also able to protect cell death caused by polyglutamine-expanded tNhtt and their combination proved to be most effective.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2009-18
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10942430-Animals, pubmed-meshheading:10942430-Brain, pubmed-meshheading:10942430-Carrier Proteins, pubmed-meshheading:10942430-Cell Death, pubmed-meshheading:10942430-Cell Line, pubmed-meshheading:10942430-Fluorescent Antibody Technique, pubmed-meshheading:10942430-HSP40 Heat-Shock Proteins, pubmed-meshheading:10942430-HSP70 Heat-Shock Proteins, pubmed-meshheading:10942430-Heat-Shock Proteins, pubmed-meshheading:10942430-Huntington Disease, pubmed-meshheading:10942430-Immunohistochemistry, pubmed-meshheading:10942430-Mice, pubmed-meshheading:10942430-Mice, Inbred Strains, pubmed-meshheading:10942430-Mice, Transgenic, pubmed-meshheading:10942430-Nerve Tissue Proteins, pubmed-meshheading:10942430-Nuclear Proteins, pubmed-meshheading:10942430-Peptides, pubmed-meshheading:10942430-Precipitin Tests, pubmed-meshheading:10942430-Protein Binding, pubmed-meshheading:10942430-Protein Folding, pubmed-meshheading:10942430-Ubiquitins
pubmed:year
2000
pubmed:articleTitle
Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity.
pubmed:affiliation
Laboratory for CAG Repeat Diseases, RIKEN Brain Science Institute, Hirosawa, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't