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N-terminal peptide fragment constitutes core of amyloid deposition of serum amyloid A: An imaging mass spectrometry study

Serum amyloid A (SAA) is an acute phase protein, which undergoes structural changes and deposits in the extracellular matrix, causing organ damage. Systemic AA amyloidosis is a relatively common amyloid subtype among the more than 30 amyloid subtypes, but the mechanism of amyloid fibril formation re...

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Autores principales: Shintani-Domoto, Yukako, Sugiura, Yuki, Ogawa, Makiko, Sugiyama, Eiji, Abe, Hiroyuki, Sakatani, Takashi, Ohashi, Ryuji, Ushiku, Tetsuo, Fukayama, Masashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9565386/
https://www.ncbi.nlm.nih.gov/pubmed/36240260
http://dx.doi.org/10.1371/journal.pone.0275993
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author Shintani-Domoto, Yukako
Sugiura, Yuki
Ogawa, Makiko
Sugiyama, Eiji
Abe, Hiroyuki
Sakatani, Takashi
Ohashi, Ryuji
Ushiku, Tetsuo
Fukayama, Masashi
author_facet Shintani-Domoto, Yukako
Sugiura, Yuki
Ogawa, Makiko
Sugiyama, Eiji
Abe, Hiroyuki
Sakatani, Takashi
Ohashi, Ryuji
Ushiku, Tetsuo
Fukayama, Masashi
author_sort Shintani-Domoto, Yukako
collection PubMed
description Serum amyloid A (SAA) is an acute phase protein, which undergoes structural changes and deposits in the extracellular matrix, causing organ damage. Systemic AA amyloidosis is a relatively common amyloid subtype among the more than 30 amyloid subtypes, but the mechanism of amyloid fibril formation remains unclear. In this study, we investigated the tissue distribution of SAA derived peptides in formalin-fixed paraffin embedded (FFPE) specimens of human myocardium with amyloidosis using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS). In the whole SAA protein, four trypsin-digested peptides in the range of SAA2-67 were visualized and the N-terminal peptide; SAA2-15, was selectively localized in the Congo red-positive region. The C-terminal peptides; SAA47-62, SAA48-62, and SAA63-67 were detected not only in the Congo red-positive region but also in the surrounding negative region. Our results demonstrate that the N-terminal SAA2-15 plays a critical role in the formation of AA amyloid fibril, as previously reported. Roles of the C-terminal peptides require further investigation.
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spelling pubmed-95653862022-10-15 N-terminal peptide fragment constitutes core of amyloid deposition of serum amyloid A: An imaging mass spectrometry study Shintani-Domoto, Yukako Sugiura, Yuki Ogawa, Makiko Sugiyama, Eiji Abe, Hiroyuki Sakatani, Takashi Ohashi, Ryuji Ushiku, Tetsuo Fukayama, Masashi PLoS One Research Article Serum amyloid A (SAA) is an acute phase protein, which undergoes structural changes and deposits in the extracellular matrix, causing organ damage. Systemic AA amyloidosis is a relatively common amyloid subtype among the more than 30 amyloid subtypes, but the mechanism of amyloid fibril formation remains unclear. In this study, we investigated the tissue distribution of SAA derived peptides in formalin-fixed paraffin embedded (FFPE) specimens of human myocardium with amyloidosis using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS). In the whole SAA protein, four trypsin-digested peptides in the range of SAA2-67 were visualized and the N-terminal peptide; SAA2-15, was selectively localized in the Congo red-positive region. The C-terminal peptides; SAA47-62, SAA48-62, and SAA63-67 were detected not only in the Congo red-positive region but also in the surrounding negative region. Our results demonstrate that the N-terminal SAA2-15 plays a critical role in the formation of AA amyloid fibril, as previously reported. Roles of the C-terminal peptides require further investigation. Public Library of Science 2022-10-14 /pmc/articles/PMC9565386/ /pubmed/36240260 http://dx.doi.org/10.1371/journal.pone.0275993 Text en © 2022 Shintani-Domoto et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Shintani-Domoto, Yukako
Sugiura, Yuki
Ogawa, Makiko
Sugiyama, Eiji
Abe, Hiroyuki
Sakatani, Takashi
Ohashi, Ryuji
Ushiku, Tetsuo
Fukayama, Masashi
N-terminal peptide fragment constitutes core of amyloid deposition of serum amyloid A: An imaging mass spectrometry study
title N-terminal peptide fragment constitutes core of amyloid deposition of serum amyloid A: An imaging mass spectrometry study
title_full N-terminal peptide fragment constitutes core of amyloid deposition of serum amyloid A: An imaging mass spectrometry study
title_fullStr N-terminal peptide fragment constitutes core of amyloid deposition of serum amyloid A: An imaging mass spectrometry study
title_full_unstemmed N-terminal peptide fragment constitutes core of amyloid deposition of serum amyloid A: An imaging mass spectrometry study
title_short N-terminal peptide fragment constitutes core of amyloid deposition of serum amyloid A: An imaging mass spectrometry study
title_sort n-terminal peptide fragment constitutes core of amyloid deposition of serum amyloid a: an imaging mass spectrometry study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9565386/
https://www.ncbi.nlm.nih.gov/pubmed/36240260
http://dx.doi.org/10.1371/journal.pone.0275993
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