• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Challenging the intracellular degradation of histones through the fusion of new technologies.

Research Project

Project/Area Number 21K19544
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research InstitutionOsaka Institute of Technology

Principal Investigator

Kawahara Ko-ichi  大阪工業大学, 工学部, 教授 (10381170)

Co-Investigator(Kenkyū-buntansha) 三浦 直樹  鹿児島大学, 農水産獣医学域獣医学系, 教授 (80508036)
外波 弘之  大阪工業大学, 工学部, 准教授 (90420405)
伊藤 隆史  鹿児島大学, 医歯学総合研究科, 特任准教授 (20381171)
八木下 尚子  聖マリアンナ医科大学, 医学研究科, 講師 (40367389)
藤田 英俊  大阪工業大学, 工学部, 准教授 (90571802)
Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2023: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2022: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords敗血症 / DAMPs / ユビキチンリガーゼ / シノビオリン / フェノールポリマー / PROTAC / ヒストン / ユビキチン
Outline of Research at the Start

敗血症の治療が確立されないのは、細胞障害時に放出されるDAMPs・ヒストンの直接的抑制方法がないからである。本研究では、ヒストンの放出抑制に新規のPROTACと改良型分子インプリンティング、すなわちフェノールポリマー法を用いる。PROTACはユビキチンリガーゼと標的タンパク質のリガンドを必要とする(キメラ化合物)。ユビキチンリガーゼにはシノビオリンを用いる。キメラ化合物の合成は親和性の強いリガンドを必要とするので、フェノールポリマー法によりキメラ化合物を同定し、細胞・動物レベルで検証する。この方法で解決されれば、敗血症に限らず、他の疾患にも応用できる。

Outline of Final Research Achievements

Treatment of sepsis requires the essential inhibition of Damage-Associated Molecular Patterns (DAMPs). Representative molecules such as histones behave as inflammatory cytokines in the extracellular environment. To avoid this, it is necessary to suppress the release of DAMPs. Therefore, we attempted to degrade DAMPs intracellularly using the phenol polymer method and the ubiquitin ligase, Synoviolin. We identified a chimeric phenol polymer capable of binding to both histones and Synoviolin. Additionally, some histones were found to directly bind to Synoviolin, indicating the possibility of ubiquitination. Thus, the potential for containment of histones during cellular damage was suggested.

Academic Significance and Societal Importance of the Research Achievements

敗血症は世界のどこかで3秒に1人が亡くなる疾患である。敗血症の定義改定により、DAMPsが注目された。間接的な細胞外での制御は困難であることが示唆され、本研究の目的「細胞内での直接的なDAMPsの封じ込めの開発・確立」は敗血症の死亡率を下げることとなり、非常に意義がある。本申請では、それぞれの分野が一義的に追求してきた課題、すなわち、医学者は敗血症の新規治療法の開発、化学者は化学合成(フェノールポリマー技術)、獣医・生物学者は細胞内シグナル伝達(ユビキチンリガーゼ・シノビオリン)の解明の融合であり、非常に意義がある。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (8 results)

All 2024 2023 2021

All Journal Article (7 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (1 results)

  • [Journal Article] Upregulation and functional roles of miR-450b in canine oral melanoma2024

    • Author(s)
      Hasan MD Nazmul、Rahman Md. Mahfuzur、Husna Al Asmaul、Arif Mohammad、Jasineviciute Indre、Kato Daiki、Nakagawa Takayuki、Miura Naoki
    • Journal Title

      Non-coding RNA Research

      Volume: 9 Issue: 2 Pages: 376-387

    • DOI

      10.1016/j.ncrna.2024.01.017

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hypoxia-related Y RNA fragments as a novel potential biomarker for distinguishing metastatic oral melanoma from non-metastatic oral melanoma in dogs2024

    • Author(s)
      Hasan MD Nazmul、Rahman MD Mahfuzur、Husna Al Asmaul、Kato Daiki、Nakagawa Takayuki、Arif Mohammad、Miura Naoki
    • Journal Title

      Veterinary Quarterly

      Volume: 44 Issue: 1 Pages: 1-8

    • DOI

      10.1080/01652176.2023.2300943

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] YRNA and tRNA fragments can differentiate benign from malignant canine mammary gland tumors2024

    • Author(s)
      Hasan MD Nazmul、Rahman Md Mahfuzur、Husna Al Asmaul、Nozaki Nobuhiro、Yamato Osamu、Miura Naoki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 691 Pages: 149336-149336

    • DOI

      10.1016/j.bbrc.2023.149336

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hypersensitivity of myelinated A-fibers via toll-like receptor 5 promotes mechanical allodynia in tenascin-X-deficient mice associated with Ehlers?Danlos syndrome2023

    • Author(s)
      Kamada Hiroki、Emura Kousuke、Yamamoto Rikuto、Kawahara Koichi、Uto Sadahito、Minami Toshiaki、Ito Seiji、Matsumoto Ken-ichi、Okuda-Ashitaka Emiko
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41598-023-45638-7

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elevated expression of miR-301a and its functional roles in canine oral melanoma2023

    • Author(s)
      Hasan MD Nazmul、Rahman Md. Mahfuzur、Husna Al Asmaul、Arif Mohammad、Iwanaga Tomoko、Tsukiyama‐Kohara Kyoko、Jasineviciute Indre、Kato Daiki、Nakagawa Takayuki、Miura Naoki
    • Journal Title

      Veterinary and Comparative Oncology

      Volume: 22 Issue: 1 Pages: 78-88

    • DOI

      10.1111/vco.12954

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] microRNAs Are Abundant and Stable in Platelet-Rich Fibrin and Other Autologous Blood Products of Canines2023

    • Author(s)
      Jasineviciute Indre、Hasan Md Nazmul、Grigas Juozas、Pautienius Arnoldas、Stankevicius Arunas、Zymantiene Judita、Miura Naoki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 1 Pages: 770-770

    • DOI

      10.3390/ijms24010770

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 1,5-Anhydro-D-fructose Protects against Rotenone-Induced Neuronal Damage In Vitro through Mitochondrial Biogenesis2021

    • Author(s)
      Kasamo Yuki、Kikuchi Kiyoshi、Yamakuchi Munekazu、Otsuka Shotaro、Takada Seiya、Kambe Yuki、Ito Takashi、Kawahara Ko-ichi、Arita Kazunori、Yoshimoto Koji、Maruyama Ikuro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 18 Pages: 9941-9941

    • DOI

      10.3390/ijms22189941

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] アスコピロンP:ERストレス時のCHOPの発現を抑制する2023

    • Author(s)
      大谷悠人、上野光理、横井春奈、吉永一浩、室屋賢康、丸山征郎、川原幸一
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Annual Research Report

URL: 

Published: 2021-07-13   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi