Decreased protein synthesis of Hsp27 associated with cellular toxicity in a cell model of Machado–Joseph disease
| Autor: | Tzu-Jung Chen, Chih-Liang Tien, Mingli Hsieh, Wei-Hsiu Chang, Nobuyuki Nukina |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
endocrine system
congenital hereditary and neonatal diseases and abnormalities animal structures Leupeptins Blotting Western HSP27 Heat-Shock Proteins Gene Expression Nerve Tissue Proteins Cysteine Proteinase Inhibitors Protein degradation Transfection medicine.disease_cause Gene product Hsp27 Stress Physiological Cell Line Tumor Heat shock protein Chlorocebus aethiops medicine Animals Humans RNA Messenger Ataxin-3 Heat-Shock Proteins Neurons biology Reverse Transcriptase Polymerase Chain Reaction General Neuroscience Nuclear Proteins Machado-Joseph Disease Polyglutamine tract medicine.disease Molecular biology Cell biology Repressor Proteins COS Cells embryonic structures biology.protein Peptides Machado–Joseph disease Oxidative stress Molecular Chaperones |
| Zdroj: | Neuroscience Letters. 454:152-156 |
| ISSN: | 0304-3940 |
| Popis: | Machado–Joseph disease is an autosomal dominant spinocerebellar degeneration caused by the expansion of a polyglutamine tract within the gene product, ataxin-3. We have previously shown that increased oxidative stress and decreased expression of Hsp27 may be contributory factors to the disease progression. In this study, we utilized neuroblastoma SK-N-SH cells stably transfected with full-length expanded ataxin-3 to further investigate the mechanism(s) resulting in the decreased expression of Hsp27. Results from 35 S-methionine pulse-chase labeling and protein degradation assays revealed that decreased Hsp27 in mutant MJD cells is due to defects in protein synthesis. Our results further demonstrated that Hsp27 degradation is independent of the proteasome degradation pathway. In addition, we showed that overexpression of Hsp27 desensitizes mutant MJD cells to apoptotic stress. Taken together, these findings provide the first evidence that expanded ataxin-3 interferes with Hsp27 synthesis, which may contribute to the impairment of the cells’ ability to respond to stresses and trigger the progression of this late-onset disease. |
| Databáze: | OpenAIRE |
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