Document Detail

Down-regulation of heat shock protein 27 in neuronal cells and non-neuronal cells expressing mutant ataxin-3.
MedLine Citation:
PMID:  12832059     Owner:  NLM     Status:  MEDLINE    
Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 is an autosomal dominant spinocerebellar degeneration characterized by a wide range of clinical manifestations. Unstable CAG trinucleotide repeat expansion in the MJD gene has been identified as the pathologic mutation of MJD. In this study, human SK-N-SH neuroblastoma cells stably transfected with full-length MJD with 78 CAG repeats were established. Compared with the parental cells, cells expressing mutant ataxin-3 displayed normal morphology for over 80 generations. Less than 1% of the transfected cells contained nuclear aggregates under basal conditions, indicating that this cellular model represented an early disease stage. While t-butyl hydroperoxide (TBH) was used to assess the oxidative tolerance of cells, the results demonstrated that the transfected cells were more susceptible to low concentrations of TBH than the parental cells. Most interestingly, from 2D gel electrophoresis analysis, we identified that the expression of heat shock protein 27 (HSP27), known as a suppressor of poly(Q)-mediated cell death, dramatically decreased in SK-N-SH cells stably transfected with full-length mutant MJD. The same reduction of HSP27 was further confirmed in lymphoblastoid cells from MJD patients. Our results demonstrated that both neuronal and non-neuronal cells with expanded full-length ataxin-3 revealed reduced protein expression of HSP27. We propose that the reduction of HSP27 in the early stage of the disease plays an important role during cell death process in MJD.
Feng-Chen Wen; Yen-Hsien Li; Hui-Fang Tsai; Chao-Hsiung Lin; Chuan Li; Chin-San Liu; Chong-Kuei Lii; Nobuyuki Nukina; Mingli Hsieh
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  FEBS letters     Volume:  546     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-06-30     Completed Date:  2003-08-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  307-14     Citation Subset:  IM    
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
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MeSH Terms
Amino Acid Sequence
Blotting, Western
Electrophoresis, Gel, Two-Dimensional
Heat-Shock Proteins / metabolism*
Molecular Sequence Data
Nerve Tissue Proteins / chemistry,  genetics,  metabolism*
Neurons / metabolism*
Nuclear Proteins
Repressor Proteins
Spectrometry, Mass, Electrospray Ionization
Trinucleotide Repeats
Tumor Cells, Cultured
Reg. No./Substance:
0/Heat-Shock Proteins; 0/Nerve Tissue Proteins; 0/Nuclear Proteins; 0/Repressor Proteins; EC 3.4.22.-/ATXN3 protein, human

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