Similarities between spinocerebellar ataxia type 7 (SCA7) cell models and human brain: proteins recruited in inclusions and activation of caspase-3
| Autor: | V. Albanese, Anne-Sophie Lebre, K. H. El Hachimi, Alexis Brice, Cecilia Zander, Hiroto Fujigasaki, Charles Duyckaerts, Junko Takahashi, Giovanni Stevanin |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Proteasome Endopeptidase Complex Ataxin 7 Recombinant Fusion Proteins Green Fluorescent Proteins Nerve Tissue Proteins Caspase 3 Biology Cell Line Multienzyme Complexes Tumor Cells Cultured Genetics medicine Humans Spinocerebellar Ataxias Ataxin-3 Child Molecular Biology Transcription factor Heat-Shock Proteins Genetics (clinical) Ataxin-7 Cell Nucleus Inclusion Bodies Neurons Microscopy Confocal HEK 293 cells Brain Nuclear Proteins General Medicine Human brain Middle Aged medicine.disease Temporal Lobe Cell biology Enzyme Activation Repressor Proteins Cysteine Endopeptidases Luminescent Proteins Microscopy Electron medicine.anatomical_structure Proteasome Cell culture Caspases Mutation Spinocerebellar ataxia biology.protein |
| Zdroj: | Human Molecular Genetics. 10:2569-2579 |
| ISSN: | 1460-2083 |
| DOI: | 10.1093/hmg/10.22.2569 |
| Popis: | Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant polyglutamine disorder presenting with progressive cerebellar ataxia and blindness. The molecular mechanisms underlying the selective neuronal death typical of SCA7 are unknown. We have established SCA7 cell culture models in HEK293 and SH-SY5Y cells, in order to analyse the effects of overexpression of the mutant ataxin-7 protein. The cells readily formed anti-ataxin-7 positive, fibrillar inclusions and small, nuclear electron dense structures. We have compared the inclusions in cells expressing mutant ataxin-7 and in human SCA7 brain tissue. There were consistent signs of ongoing abnormal protein folding, including the recruitment of heat-shock proteins and proteasome subunits. Occasionally, sequestered transcription factors were found. Activated caspase-3 was recruited into the inclusions in both the cell models and human SCA7 brain and its expression was upregulated in cortical neurones, suggesting that it may play a role in the disease process. Finally, on the ultrastructural level, there were signs of autophagy and nuclear indentations, indicative of a major stress response in cells expressing mutant ataxin-7. |
| Databáze: | OpenAIRE |
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