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Proteomic Analysis of Highly Prevalent Amyloid A Amyloidosis Endemic to Endangered Island Foxes
Amyloid A (AA) amyloidosis is a debilitating, often fatal, systemic amyloid disease associated with chronic inflammation and persistently elevated serum amyloid A (SAA). Elevated SAA is necessary but not sufficient to cause disease and the risk factors for AA amyloidosis remain poorly understood. He...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245998/ https://www.ncbi.nlm.nih.gov/pubmed/25429466 http://dx.doi.org/10.1371/journal.pone.0113765 |
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author | Gaffney, Patricia M. Imai, Denise M. Clifford, Deana L. Ghassemian, Majid Sasik, Roman Chang, Aaron N. O’Brien, Timothy D. Coppinger, Judith Trejo, Margarita Masliah, Eliezer Munson, Linda Sigurdson, Christina |
author_facet | Gaffney, Patricia M. Imai, Denise M. Clifford, Deana L. Ghassemian, Majid Sasik, Roman Chang, Aaron N. O’Brien, Timothy D. Coppinger, Judith Trejo, Margarita Masliah, Eliezer Munson, Linda Sigurdson, Christina |
author_sort | Gaffney, Patricia M. |
collection | PubMed |
description | Amyloid A (AA) amyloidosis is a debilitating, often fatal, systemic amyloid disease associated with chronic inflammation and persistently elevated serum amyloid A (SAA). Elevated SAA is necessary but not sufficient to cause disease and the risk factors for AA amyloidosis remain poorly understood. Here we identify an extraordinarily high prevalence of AA amyloidosis (34%) in a genetically isolated population of island foxes (Urocyon littoralis) with concurrent chronic inflammatory diseases. Amyloid deposits were most common in kidney (76%), spleen (58%), oral cavity (45%), and vasculature (44%) and were composed of unbranching, 10 nm in diameter fibrils. Peptide sequencing by mass spectrometry revealed that SAA peptides were dominant in amyloid-laden kidney, together with high levels of apolipoprotein E, apolipoprotein A-IV, fibrinogen-α chain, and complement C3 and C4 (false discovery rate ≤0.05). Reassembled peptide sequences showed island fox SAA as an 111 amino acid protein, most similar to dog and artic fox, with 5 unique amino acid variants among carnivores. SAA peptides extended to the last two C-terminal amino acids in 5 of 9 samples, indicating that near full length SAA was often present in amyloid aggregates. These studies define a remarkably prevalent AA amyloidosis in island foxes with widespread systemic amyloid deposition, a unique SAA sequence, and the co-occurrence of AA with apolipoproteins. |
format | Online Article Text |
id | pubmed-4245998 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42459982014-12-05 Proteomic Analysis of Highly Prevalent Amyloid A Amyloidosis Endemic to Endangered Island Foxes Gaffney, Patricia M. Imai, Denise M. Clifford, Deana L. Ghassemian, Majid Sasik, Roman Chang, Aaron N. O’Brien, Timothy D. Coppinger, Judith Trejo, Margarita Masliah, Eliezer Munson, Linda Sigurdson, Christina PLoS One Research Article Amyloid A (AA) amyloidosis is a debilitating, often fatal, systemic amyloid disease associated with chronic inflammation and persistently elevated serum amyloid A (SAA). Elevated SAA is necessary but not sufficient to cause disease and the risk factors for AA amyloidosis remain poorly understood. Here we identify an extraordinarily high prevalence of AA amyloidosis (34%) in a genetically isolated population of island foxes (Urocyon littoralis) with concurrent chronic inflammatory diseases. Amyloid deposits were most common in kidney (76%), spleen (58%), oral cavity (45%), and vasculature (44%) and were composed of unbranching, 10 nm in diameter fibrils. Peptide sequencing by mass spectrometry revealed that SAA peptides were dominant in amyloid-laden kidney, together with high levels of apolipoprotein E, apolipoprotein A-IV, fibrinogen-α chain, and complement C3 and C4 (false discovery rate ≤0.05). Reassembled peptide sequences showed island fox SAA as an 111 amino acid protein, most similar to dog and artic fox, with 5 unique amino acid variants among carnivores. SAA peptides extended to the last two C-terminal amino acids in 5 of 9 samples, indicating that near full length SAA was often present in amyloid aggregates. These studies define a remarkably prevalent AA amyloidosis in island foxes with widespread systemic amyloid deposition, a unique SAA sequence, and the co-occurrence of AA with apolipoproteins. Public Library of Science 2014-11-26 /pmc/articles/PMC4245998/ /pubmed/25429466 http://dx.doi.org/10.1371/journal.pone.0113765 Text en © 2014 Gaffney et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Gaffney, Patricia M. Imai, Denise M. Clifford, Deana L. Ghassemian, Majid Sasik, Roman Chang, Aaron N. O’Brien, Timothy D. Coppinger, Judith Trejo, Margarita Masliah, Eliezer Munson, Linda Sigurdson, Christina Proteomic Analysis of Highly Prevalent Amyloid A Amyloidosis Endemic to Endangered Island Foxes |
title | Proteomic Analysis of Highly Prevalent Amyloid A Amyloidosis Endemic to Endangered Island Foxes |
title_full | Proteomic Analysis of Highly Prevalent Amyloid A Amyloidosis Endemic to Endangered Island Foxes |
title_fullStr | Proteomic Analysis of Highly Prevalent Amyloid A Amyloidosis Endemic to Endangered Island Foxes |
title_full_unstemmed | Proteomic Analysis of Highly Prevalent Amyloid A Amyloidosis Endemic to Endangered Island Foxes |
title_short | Proteomic Analysis of Highly Prevalent Amyloid A Amyloidosis Endemic to Endangered Island Foxes |
title_sort | proteomic analysis of highly prevalent amyloid a amyloidosis endemic to endangered island foxes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245998/ https://www.ncbi.nlm.nih.gov/pubmed/25429466 http://dx.doi.org/10.1371/journal.pone.0113765 |
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