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Co-precipitation molecules hemopexin and transferrin may be key molecules for fibrillogenesis in TTR V30M amyloidogenesis
The disease model of familial amyloidotic polyneuropathy—7.2-hMet30 mice—manifests amyloid deposition that consists of a human amyloidogenic mutant transthyretin (TTR) (TTR V30M). Our previous study found amyloid deposits in 14 of 27 7.2-hMet30 mice at 21–24 months of age. In addition, non-fibrillar...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847157/ https://www.ncbi.nlm.nih.gov/pubmed/29288430 http://dx.doi.org/10.1007/s11248-017-0054-x |
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author | Ohta, Mika Sugano, Aki Hatano, Naoya Sato, Hirotaka Shimada, Hirofumi Niwa, Hitoshi Sakaeda, Toshiyuki Tei, Hajime Sakaki, Yoshiyuki Yamamura, Ken-ichi Takaoka, Yutaka |
author_facet | Ohta, Mika Sugano, Aki Hatano, Naoya Sato, Hirotaka Shimada, Hirofumi Niwa, Hitoshi Sakaeda, Toshiyuki Tei, Hajime Sakaki, Yoshiyuki Yamamura, Ken-ichi Takaoka, Yutaka |
author_sort | Ohta, Mika |
collection | PubMed |
description | The disease model of familial amyloidotic polyneuropathy—7.2-hMet30 mice—manifests amyloid deposition that consists of a human amyloidogenic mutant transthyretin (TTR) (TTR V30M). Our previous study found amyloid deposits in 14 of 27 7.2-hMet30 mice at 21–24 months of age. In addition, non-fibrillar TTR deposits were found in amyloid-negative 7.2hMet30 mice. These results suggested that TTR amyloidogenesis required not only mutant TTR but also an additional factor (or factors) as an etiologic molecule. To determine the differences in serum proteome in amyloid-positive and amyloid-negative mice in the 7.2-hMet30 model, we used proteomic analyses and studied serum samples obtained from these mice. Hemopexin (HPX) and transferrin (Tf) were detected in the serum samples from amyloid-positive mice and were also found in amyloid deposits via immunohistochemistry, but serum samples from amyloid-negative mice did not contain HPX and Tf. These two proteins were also not detected in non-fibrillar TTR deposits. In addition, in silico analyses suggested that HPX and Tf facilitate destabilization of TTR secondary structures and misfolding of TTR. These results suggest that HPX and Tf may be associated with TTR amyloidogenesis after fibrillogenesis in vivo. |
format | Online Article Text |
id | pubmed-5847157 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-58471572018-03-20 Co-precipitation molecules hemopexin and transferrin may be key molecules for fibrillogenesis in TTR V30M amyloidogenesis Ohta, Mika Sugano, Aki Hatano, Naoya Sato, Hirotaka Shimada, Hirofumi Niwa, Hitoshi Sakaeda, Toshiyuki Tei, Hajime Sakaki, Yoshiyuki Yamamura, Ken-ichi Takaoka, Yutaka Transgenic Res Original Article The disease model of familial amyloidotic polyneuropathy—7.2-hMet30 mice—manifests amyloid deposition that consists of a human amyloidogenic mutant transthyretin (TTR) (TTR V30M). Our previous study found amyloid deposits in 14 of 27 7.2-hMet30 mice at 21–24 months of age. In addition, non-fibrillar TTR deposits were found in amyloid-negative 7.2hMet30 mice. These results suggested that TTR amyloidogenesis required not only mutant TTR but also an additional factor (or factors) as an etiologic molecule. To determine the differences in serum proteome in amyloid-positive and amyloid-negative mice in the 7.2-hMet30 model, we used proteomic analyses and studied serum samples obtained from these mice. Hemopexin (HPX) and transferrin (Tf) were detected in the serum samples from amyloid-positive mice and were also found in amyloid deposits via immunohistochemistry, but serum samples from amyloid-negative mice did not contain HPX and Tf. These two proteins were also not detected in non-fibrillar TTR deposits. In addition, in silico analyses suggested that HPX and Tf facilitate destabilization of TTR secondary structures and misfolding of TTR. These results suggest that HPX and Tf may be associated with TTR amyloidogenesis after fibrillogenesis in vivo. Springer International Publishing 2017-12-29 2018 /pmc/articles/PMC5847157/ /pubmed/29288430 http://dx.doi.org/10.1007/s11248-017-0054-x Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Article Ohta, Mika Sugano, Aki Hatano, Naoya Sato, Hirotaka Shimada, Hirofumi Niwa, Hitoshi Sakaeda, Toshiyuki Tei, Hajime Sakaki, Yoshiyuki Yamamura, Ken-ichi Takaoka, Yutaka Co-precipitation molecules hemopexin and transferrin may be key molecules for fibrillogenesis in TTR V30M amyloidogenesis |
title | Co-precipitation molecules hemopexin and transferrin may be key molecules for fibrillogenesis in TTR V30M amyloidogenesis |
title_full | Co-precipitation molecules hemopexin and transferrin may be key molecules for fibrillogenesis in TTR V30M amyloidogenesis |
title_fullStr | Co-precipitation molecules hemopexin and transferrin may be key molecules for fibrillogenesis in TTR V30M amyloidogenesis |
title_full_unstemmed | Co-precipitation molecules hemopexin and transferrin may be key molecules for fibrillogenesis in TTR V30M amyloidogenesis |
title_short | Co-precipitation molecules hemopexin and transferrin may be key molecules for fibrillogenesis in TTR V30M amyloidogenesis |
title_sort | co-precipitation molecules hemopexin and transferrin may be key molecules for fibrillogenesis in ttr v30m amyloidogenesis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847157/ https://www.ncbi.nlm.nih.gov/pubmed/29288430 http://dx.doi.org/10.1007/s11248-017-0054-x |
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