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Formation of soluble amyloid oligomers and amyloid fibrils by the multifunctional protein vitronectin

BACKGROUND: The multifunctional protein vitronectin is present within the deposits associated with Alzheimer disease (AD), age-related macular degeneration (AMD), atherosclerosis, systemic amyloidoses, and glomerulonephritis. The extent to which vitronectin contributes to amyloid formation within th...

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Autores principales: Shin, Thuzar M, Isas, J Mario, Hsieh, Chia-Ling, Kayed, Rakez, Glabe, Charles G, Langen, Ralf, Chen, Jeannie
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577670/
https://www.ncbi.nlm.nih.gov/pubmed/18939994
http://dx.doi.org/10.1186/1750-1326-3-16
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author Shin, Thuzar M
Isas, J Mario
Hsieh, Chia-Ling
Kayed, Rakez
Glabe, Charles G
Langen, Ralf
Chen, Jeannie
author_facet Shin, Thuzar M
Isas, J Mario
Hsieh, Chia-Ling
Kayed, Rakez
Glabe, Charles G
Langen, Ralf
Chen, Jeannie
author_sort Shin, Thuzar M
collection PubMed
description BACKGROUND: The multifunctional protein vitronectin is present within the deposits associated with Alzheimer disease (AD), age-related macular degeneration (AMD), atherosclerosis, systemic amyloidoses, and glomerulonephritis. The extent to which vitronectin contributes to amyloid formation within these plaques, which contain misfolded, amyloidogenic proteins, and the role of vitronectin in the pathophysiology of the aforementioned diseases is currently unknown. The investigation of vitronectin aggregation is significant since the formation of oligomeric and fibrillar structures are common features of amyloid proteins. RESULTS: We observed vitronectin immunoreactivity in senile plaques of AD brain, which exhibited overlap with the amyloid fibril-specific OC antibody, suggesting that vitronectin is deposited at sites of amyloid formation. Of particular interest is the growing body of evidence indicating that soluble nonfibrillar oligomers may be responsible for the development and progression of amyloid diseases. In this study we demonstrate that both plasma-purified and recombinant human vitronectin readily form spherical oligomers and typical amyloid fibrils. Vitronectin oligomers are toxic to cultured neuroblastoma and retinal pigment epithelium (RPE) cells, possibly via a membrane-dependent mechanism, as they cause leakage of synthetic vesicles. Oligomer toxicity was attenuated in RPE cells by the anti-oligomer A11 antibody. Vitronectin fibrils contain a C-terminal protease-resistant fragment, which may approximate the core region of residues essential to amyloid formation. CONCLUSION: These data reveal the propensity of vitronectin to behave as an amyloid protein and put forth the possibilities that accumulation of misfolded vitronectin may contribute to aggregate formation seen in age-related amyloid diseases.
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spelling pubmed-25776702008-11-04 Formation of soluble amyloid oligomers and amyloid fibrils by the multifunctional protein vitronectin Shin, Thuzar M Isas, J Mario Hsieh, Chia-Ling Kayed, Rakez Glabe, Charles G Langen, Ralf Chen, Jeannie Mol Neurodegener Research Article BACKGROUND: The multifunctional protein vitronectin is present within the deposits associated with Alzheimer disease (AD), age-related macular degeneration (AMD), atherosclerosis, systemic amyloidoses, and glomerulonephritis. The extent to which vitronectin contributes to amyloid formation within these plaques, which contain misfolded, amyloidogenic proteins, and the role of vitronectin in the pathophysiology of the aforementioned diseases is currently unknown. The investigation of vitronectin aggregation is significant since the formation of oligomeric and fibrillar structures are common features of amyloid proteins. RESULTS: We observed vitronectin immunoreactivity in senile plaques of AD brain, which exhibited overlap with the amyloid fibril-specific OC antibody, suggesting that vitronectin is deposited at sites of amyloid formation. Of particular interest is the growing body of evidence indicating that soluble nonfibrillar oligomers may be responsible for the development and progression of amyloid diseases. In this study we demonstrate that both plasma-purified and recombinant human vitronectin readily form spherical oligomers and typical amyloid fibrils. Vitronectin oligomers are toxic to cultured neuroblastoma and retinal pigment epithelium (RPE) cells, possibly via a membrane-dependent mechanism, as they cause leakage of synthetic vesicles. Oligomer toxicity was attenuated in RPE cells by the anti-oligomer A11 antibody. Vitronectin fibrils contain a C-terminal protease-resistant fragment, which may approximate the core region of residues essential to amyloid formation. CONCLUSION: These data reveal the propensity of vitronectin to behave as an amyloid protein and put forth the possibilities that accumulation of misfolded vitronectin may contribute to aggregate formation seen in age-related amyloid diseases. BioMed Central 2008-10-21 /pmc/articles/PMC2577670/ /pubmed/18939994 http://dx.doi.org/10.1186/1750-1326-3-16 Text en Copyright © 2008 Shin et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Shin, Thuzar M
Isas, J Mario
Hsieh, Chia-Ling
Kayed, Rakez
Glabe, Charles G
Langen, Ralf
Chen, Jeannie
Formation of soluble amyloid oligomers and amyloid fibrils by the multifunctional protein vitronectin
title Formation of soluble amyloid oligomers and amyloid fibrils by the multifunctional protein vitronectin
title_full Formation of soluble amyloid oligomers and amyloid fibrils by the multifunctional protein vitronectin
title_fullStr Formation of soluble amyloid oligomers and amyloid fibrils by the multifunctional protein vitronectin
title_full_unstemmed Formation of soluble amyloid oligomers and amyloid fibrils by the multifunctional protein vitronectin
title_short Formation of soluble amyloid oligomers and amyloid fibrils by the multifunctional protein vitronectin
title_sort formation of soluble amyloid oligomers and amyloid fibrils by the multifunctional protein vitronectin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577670/
https://www.ncbi.nlm.nih.gov/pubmed/18939994
http://dx.doi.org/10.1186/1750-1326-3-16
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