| Concanavalin A aggregation and toxicity on cell cultures. | |
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MedLine Citation:
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PMID: 19782769 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A number of neurodegenerative diseases are known to involve protein aggregation. Common mechanisms and structural properties of amyloids are thought to be involved in aggregation-related cytotoxicity. In this context we propose an experimental study on Concanavalin A (Con A) aggregation and use it as a model to study the relationship between cell toxicity and aggregation processes. Depending on solution conditions, Con A aggregation has been monitored by static and dynamic light scattering, Thioflavin T emission, and FTIR absorption. The morphology of different aggregate species was verified by means of Atomic Force Microscopy and Confocal Microscopy. During the aggregation pathway the native protein conformation is destabilized and as a consequence, the simultaneous occurrence of conformational changes and protein aggregation is observed in both conditions. The effects of the extracellular addition of native protein, oligomers and mature fibrils were tested on LAN5 neuroblastoma cells by MTS assay. Results showed the toxicity of the first two species while a negligible effect was detected for amyloid fibrils. Both native and oligomeric aggregates were found to be able to activate apoptosis exclusively by extrinsic pathway through caspase 8 activation. Those results suggest that cytotoxicity mechanisms arise from specific membrane interactions with reactive conformations of destabilized molecules occurring during the amyloidal aggregation pathway. Those conformations, populated when native or preformed oligomers are incubated, are unavailable to bind cell membrane proteins. This happens because they are recruited in the mature fibrillar structure which-as a consequence-turns out to be non-toxic. |
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Authors:
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Valeria Vetri; Rita Carrotta; Pasquale Picone; Marta Di Carlo; Valeria Militello |
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Publication Detail:
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Type: Journal Article Date: 2009-09-25 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1804 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2009-11-25 Completed Date: 2010-03-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 173-83 Citation Subset: IM |
Affiliation:
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Dipartimento di Scienze Fisiche ed Astronomiche, Universit? di Palermo and CNISM-MeSIAM, 90123 Palermo, Italy. valeria.vetri@fisica.unipa.it |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amyloid
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chemistry* Apoptosis / drug effects Cell Line, Tumor Cell Survival Concanavalin A / metabolism*, pharmacology Humans Microscopy, Atomic Force Neurons / metabolism Protein Structure, Quaternary* Spectroscopy, Fourier Transform Infrared |
| Chemical | |
Reg. No./Substance:
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0/Amyloid; 11028-71-0/Concanavalin A |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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