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Mechanism of fibril formation of human lysozyme mutants and analysis of its toxicity in the amyloid disease model mice

Research Project

Project/Area Number 25450476
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Integrative animal science
Research InstitutionKagoshima University

Principal Investigator

Sugimoto Yasushi  鹿児島大学, 農水産獣医学域農学系, 教授 (10100736)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsリゾチーム / アミロイド線維 / 分子シャペロン / 小胞体ストレス / GRP78/BiP / トランスサイレチン / トランスジェニックマウス / アミロイド病 / 変異体 / フォールディング / ERストレス / UPR / アミロイドーシス / タンパク質凝集体 / アポトーシス
Outline of Final Research Achievements

The toxicity of the human lysozyme mutants that cause a systemic amyloidosis could be verified at the cellular level and the biological level. Lysozyme mutants accumulate in the endoplasmic reticulum, remaining bound to molecular chaperone GRP78 / BiP. The accumulation of both proteins result in activating the IRE1-XBP1-GRP78 / BiP pathway, which induces endoplasmic reticulum stress. Transthyretin mutants accumulated in the endoplasmic reticulum and activated the IRE1-XBP1-GRP78 / BiP pathway and induced ER stress as well as lysozyme. Furthermore, transthyretin mutants remained bound to GRP78 / BiP. Amyloidosis caused by abnormal secreted proteins might have in common. Aggregating proteins tend to form amyloid fibrils and accumulate in the endoplasmic reticulum and provide damage for cell. Cell damage lead to loss of the cell function and cell death. In conclusion, amyloidosis of lysozyme is assumed to be caused by the accumulation of abnormal protein in the cell over long period.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (15 results)

All 2016 2015 2014 2013

All Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Open Access: 8 results,  Acknowledgement Compliant: 4 results) Presentation (6 results)

  • [Journal Article] Lysozyme Mutants Accumulate in Cells while Associated at their N-terminal Alpha-domain with the Endoplasmic Reticulum Chaperone GRP78/BiP.2016

    • Author(s)
      Kamada Y, Nawata Y, Sugimoto Y.
    • Journal Title

      Int. J. Biol. Sci.

      Volume: 12 Issue: 2 Pages: 184-197

    • DOI

      10.7150/ijbs.13710

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Amyloidogenic lysozymes accumulate in the endoplasmic reticulum accompanied by the augmentation of ER stress signals.2015

    • Author(s)
      Kamada Y, Kusakabe T, Sugimoto Y.
    • Journal Title

      Biochim. Biophys. Acta.

      Volume: 1850 Pages: 1107-1119

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Heat shock protein 90 acts in brassinosteroid signaling through interaction with BES1/BZR1 transcription factor.2015

    • Author(s)
      Shigeta T, Zaizen Y, Sugimoto Y, Nakamura Y, Matsuo T, Okamoto S.
    • Journal Title

      J. Plant Physiol.

      Volume: 178 Pages: 69-73

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ethanol extract of Brazilian propolis ameliorates cognitive dysfunction and suppressed protein aggregations caused by hyperhomocysteinemia.2015

    • Author(s)
      Miyazaki Y, Sugimoto Y, Fujita A, Kanouchi H.
    • Journal Title

      Biosci. Biotechnol. Biochem.

      Volume: 79 Pages: 1884-1889

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Amyloid fibril formation from a 9 amino acid peptide, 55th-63rd residues of human lysozyme.2015

    • Author(s)
      Tokunaga Y, Matsumoto M, Sugimoto Y.
    • Journal Title

      Int. J. Biol. Macromol.

      Volume: 80 Pages: 208-216

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Amyloidogenic lysozymes accumulate in the endoplasmic reticulum accompanied by the augmentation of ER stress signals.2015

    • Author(s)
      Kamada Y, Kusakabe T, Sugimoto Y.
    • Journal Title

      Biochim Biophys Acta

      Volume: 1850 Pages: 1107-1119

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Heat shock protein 90 acts in brassinosteroid signaling through interaction with BES1/BZR1 transcription factor.2015

    • Author(s)
      Shigeta T, Zaizen Y, Sugimoto Y, Nakamura Y, Matsuo T, Okamoto S.
    • Journal Title

      Journal of Plant Physiology

      Volume: 178 Pages: 69-73

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular evidence of the involvement of heat shock protein 90 in brassinosteroid signaling in Arabidopsis T87 cultured cells.2014

    • Author(s)
      Shigeta T, Zaizen Y, Asami T, Yoshida S, Nakamura Y, Okamoto S, Matsuo T, Sugimoto Y.
    • Journal Title

      Plant Cell Report

      Volume: 33 Issue: 3 Pages: 499-510

    • DOI

      10.1007/s00299-013-1550-y

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Amyloid fibril formation in vitro from halophilic metal binding protein: its high solubility and reversibility minimized formation of amorphous protein aggregations.2013

    • Author(s)
      Tokunaga Y, Matsumoto M, Tokunaga M, Arakawa T, Sugimoto Y.
    • Journal Title

      Protein Science

      Volume: 22(11) Issue: 11 Pages: 1582-1591

    • DOI

      10.1002/pro.2359

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] アミロイドジェニックリゾチームはGRP78/BiPと小胞体内に蓄積し、小胞体ストレスを誘発する2015

    • Author(s)
      縄田 勇介 , 釜田 佳季, 新田 絢乃, 田中 志穂実, 杉元 康志
    • Organizer
      第 38回日本分子生物学会年会、第 88回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド( 兵庫県神戸市 )
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] リゾチーム変異体の小胞体への蓄積と小胞体ストレス2014

    • Author(s)
      杉元 康志, 釜田 佳季, 縄田 勇介
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パシフィコ 横浜 ( 神奈川県、横浜市)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] リゾチームアミロイド線維の細胞毒性について2013

    • Author(s)
      釜田佳季、中屋直仁、杉元康志
    • Organizer
      日本生化学会九州支部例会
    • Place of Presentation
      佐賀大学
    • Related Report
      2013 Research-status Report
  • [Presentation] リゾチームアミロイド線維形成コアペプチドのシーズ効2013

    • Author(s)
      有馬拓広、徳永雄平、縄田勇介、釜田佳季、杉元康志、渡邉啓一
    • Organizer
      日本生化学会九州支部例会
    • Place of Presentation
      佐賀大学
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒトリゾチーム変異体発現による凝集体の解析2013

    • Author(s)
      釜田 佳季,縄田 勇介,懸野崎 知世,杉元 康志,
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2013 Research-status Report
  • [Presentation] ピキア酵母におけるヒトリゾチーム変異体の遺伝子発現とタンパク産生2013

    • Author(s)
      有馬 拓広,中屋 直仁,釜田 佳季,田代 康介,久原 哲,杉元 康志
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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