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Polyglutamine expansion, protein aggregation, proteasome activity, and neural survival.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2002 Apr 19; Vol. 277 (16), pp. 13935-42. Date of Electronic Publication: 2002 Jan 08. - Publication Year :
- 2002
-
Abstract
- Huntington's disease (HD) is one of eight established triplet repeat neurodegenerative disorders, which are collectively caused by the genetic expansion of polyglutamine repeats. While the mechanism(s) by which polyglutamine expansion causes neurodegeneration in each of these disorders is being intensely investigated, the underlying cause of polyglutamine toxicity has not been fully elucidated. A number of studies have focused on the potential role of protein aggregation and disruption of the proteasome proteolytic pathway in polyglutamine-mediated neurodegeneration. However, at present it is not clear whether polyglutamine-mediated protein aggregation is sufficient to induce cell death, nor has it been clearly determined whether proteasome inhibition precedes, coincides, or occurs as the result of the formation of polyglutamine-associated protein aggregation. To address these important components of polyglutamine toxicity, in the present study we utilized neural SH-SY5Y cells stably transfected with polyglutamine-green fluorescent protein constructs to examine the effects of polyglutamine expansion on protein aggregation, proteasome activity, and neural cell survival. Data from the present study demonstrate that polyglutamine expansion does not dramatically impair proteasome activity or elevate protein aggregate formation under basal conditions, but does significantly impair the ability of the proteasome to respond to stress, and increases stress-induced protein aggregation following stress, all in the absence of neural cell death.
- Subjects :
- Blotting, Northern
Blotting, Western
Cell Division
Cell Line
Cell Survival
Dose-Response Relationship, Drug
Green Fluorescent Proteins
Hot Temperature
Humans
Luminescent Proteins metabolism
Proteasome Endopeptidase Complex
Protein Binding
Recombinant Fusion Proteins metabolism
Time Factors
Transfection
Cysteine Endopeptidases metabolism
Multienzyme Complexes metabolism
Neurons metabolism
Peptides genetics
Peptides metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 277
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 11782460
- Full Text :
- https://doi.org/10.1074/jbc.M107706200