Co-precipitation molecules hemopexin and transferrin may be key molecules for fibrillogenesis in TTR V30M amyloidogenesis

Mika Ohta, Aki Sugano, Naoya Hatano, Hirotaka Sato, Hirofumi Shimada, Hitoshi Niwa, Toshiyuki Sakaeda, Hajime Tei, Yoshiyuki Sakaki, Ken ichi Yamamura, Yutaka Takaoka

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)15-23
Number of pages9
JournalTransgenic Research
Volume27
Issue number1
DOIs
Publication statusPublished - Feb 1 2018
Externally publishedYes

Keywords

  • Hemopexin
  • Molecular dynamics simulation
  • Proteomic analysis
  • TTR amyloidogenesis
  • Transferrin

ASJC Scopus subject areas

  • Biotechnology
  • Animal Science and Zoology
  • Agronomy and Crop Science
  • Genetics

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  • Cite this

    Ohta, M., Sugano, A., Hatano, N., Sato, H., Shimada, H., Niwa, H., Sakaeda, T., Tei, H., Sakaki, Y., Yamamura, K. I., & Takaoka, Y. (2018). Co-precipitation molecules hemopexin and transferrin may be key molecules for fibrillogenesis in TTR V30M amyloidogenesis. Transgenic Research, 27(1), 15-23. https://doi.org/10.1007/s11248-017-0054-x