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Oxidative Stress Alters the Morphology and Toxicity of Aortic Medial Amyloid
The aggregation and fibril deposition of amyloid proteins have been implicated in a range of neurodegenerative and vascular diseases, and yet the underlying molecular mechanisms are poorly understood. Here, we use a combination of cell-based assays, biophysical analysis, and atomic force microscopy...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Biophysical Society
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4675884/ https://www.ncbi.nlm.nih.gov/pubmed/26636947 http://dx.doi.org/10.1016/j.bpj.2015.10.034 |
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author | Davies, Hannah A. Phelan, Marie M. Wilkinson, Mark C. Migrino, Raymond Q. Truran, Seth Franco, Daniel A. Liu, Lu-Ning Longmore, Christopher J. Madine, Jillian |
author_facet | Davies, Hannah A. Phelan, Marie M. Wilkinson, Mark C. Migrino, Raymond Q. Truran, Seth Franco, Daniel A. Liu, Lu-Ning Longmore, Christopher J. Madine, Jillian |
author_sort | Davies, Hannah A. |
collection | PubMed |
description | The aggregation and fibril deposition of amyloid proteins have been implicated in a range of neurodegenerative and vascular diseases, and yet the underlying molecular mechanisms are poorly understood. Here, we use a combination of cell-based assays, biophysical analysis, and atomic force microscopy to investigate the potential involvement of oxidative stress in aortic medial amyloid (AMA) pathogenesis and deposition. We show that medin, the main constituent of AMA, can induce an environment rich in oxidative species, increasing superoxide and reducing bioavailable nitric oxide in human cells. We investigate the role that this oxidative environment may play in altering the aggregation process of medin and identify potential posttranslational modification sites where site-specific modification and interaction can be unambiguously demonstrated. In an oxidizing environment, medin is nitrated at tyrosine and tryptophan residues, with resultant effects on morphology that lead to longer fibrils with increased toxicity. This provides further motivation to investigate the role of oxidative stress in AMA pathogenicity. |
format | Online Article Text |
id | pubmed-4675884 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Biophysical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-46758842016-12-01 Oxidative Stress Alters the Morphology and Toxicity of Aortic Medial Amyloid Davies, Hannah A. Phelan, Marie M. Wilkinson, Mark C. Migrino, Raymond Q. Truran, Seth Franco, Daniel A. Liu, Lu-Ning Longmore, Christopher J. Madine, Jillian Biophys J Proteins and Nucleic Acids The aggregation and fibril deposition of amyloid proteins have been implicated in a range of neurodegenerative and vascular diseases, and yet the underlying molecular mechanisms are poorly understood. Here, we use a combination of cell-based assays, biophysical analysis, and atomic force microscopy to investigate the potential involvement of oxidative stress in aortic medial amyloid (AMA) pathogenesis and deposition. We show that medin, the main constituent of AMA, can induce an environment rich in oxidative species, increasing superoxide and reducing bioavailable nitric oxide in human cells. We investigate the role that this oxidative environment may play in altering the aggregation process of medin and identify potential posttranslational modification sites where site-specific modification and interaction can be unambiguously demonstrated. In an oxidizing environment, medin is nitrated at tyrosine and tryptophan residues, with resultant effects on morphology that lead to longer fibrils with increased toxicity. This provides further motivation to investigate the role of oxidative stress in AMA pathogenicity. The Biophysical Society 2015-12-01 2015-12-01 /pmc/articles/PMC4675884/ /pubmed/26636947 http://dx.doi.org/10.1016/j.bpj.2015.10.034 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Proteins and Nucleic Acids Davies, Hannah A. Phelan, Marie M. Wilkinson, Mark C. Migrino, Raymond Q. Truran, Seth Franco, Daniel A. Liu, Lu-Ning Longmore, Christopher J. Madine, Jillian Oxidative Stress Alters the Morphology and Toxicity of Aortic Medial Amyloid |
title | Oxidative Stress Alters the Morphology and Toxicity of Aortic Medial Amyloid |
title_full | Oxidative Stress Alters the Morphology and Toxicity of Aortic Medial Amyloid |
title_fullStr | Oxidative Stress Alters the Morphology and Toxicity of Aortic Medial Amyloid |
title_full_unstemmed | Oxidative Stress Alters the Morphology and Toxicity of Aortic Medial Amyloid |
title_short | Oxidative Stress Alters the Morphology and Toxicity of Aortic Medial Amyloid |
title_sort | oxidative stress alters the morphology and toxicity of aortic medial amyloid |
topic | Proteins and Nucleic Acids |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4675884/ https://www.ncbi.nlm.nih.gov/pubmed/26636947 http://dx.doi.org/10.1016/j.bpj.2015.10.034 |
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