Ectoine alters subcellular localization of inclusions and reduces apoptotic cell death induced by the truncated Machado–Joseph disease gene product with an expanded polyglutamine stretch
| Autor: | Shin'ichi Shoji, Kentaro Furusho, Toshihiro Yoshizawa |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cytoplasm
Protein Folding Cytoplasmic inclusion Down-Regulation Apoptosis Nerve Tissue Proteins Ectoine Biology lcsh:RC321-571 Gene product Mice chemistry.chemical_compound Gastrointestinal Agents Cell Line Tumor Animals Nuclear protein Ataxin-3 lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Cell Nucleus Inclusion Bodies Neurons Inclusion Dose-Response Relationship Drug Amino Acids Diamino Nuclear Proteins Compatible solute Machado-Joseph Disease Polyglutamine tract Subcellular localization Cell biology Betaine Repressor Proteins Neuroprotective Agents Neurology Biochemistry chemistry Nerve Degeneration Osmoprotectant Chemical chaperone Peptides Trinucleotide Repeat Expansion Polyglutamine Transcription Factors Machado–Joseph disease |
| Zdroj: | Neurobiology of Disease, Vol 20, Iss 1, Pp 170-178 (2005) |
| ISSN: | 0969-9961 |
| DOI: | 10.1016/j.nbd.2005.02.011 |
| Popis: | Protein misfolding is considered a key event in the pathogenesis of polyglutamine disease such as Machado-Joseph disease (MJD). Overexpression of chaperone proteins and the application of chemical chaperones are reported to suppress polyglutamine induced cytotoxicity in vitro and in vivo. The effects of compatible solutes, which are osmoprotectants in bacteria and possess the action in stabilizing proteins under stress, have not, to our knowledge, been studied. We explored the protective effects of the compatible solutes ectoine, hydroxyectoine, and betaine on apoptotic cell death produced by the truncated MJD gene product with an expanded polyglutamine tract in cultured neuro2a cells. Ectoine, but not hydroxyectoine or betaine, decreased large cytoplasmic inclusions and increased the frequency of nuclear inclusions. Immunoblot analysis showed that ectoine reduced the total amount of aggregates. Despite the presence of nuclear inclusions, apoptotic features were less frequently observed after ectoine application. Our findings suggest that ectoine, a natural osmoprotectant in bacteria, may function as a novel molecule protecting cells from polyglutamine-induced toxicity. |
| Databáze: | OpenAIRE |
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