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Study on the role of CO as a signaling molecule in cell differentiation

Research Project

Project/Area Number 19K22260
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 37:Biomolecular chemistry and related fields
Research InstitutionDoshisha University

Principal Investigator

Kitagishi Hiroaki  同志社大学, 理工学部, 教授 (60448090)

Co-Investigator(Kenkyū-buntansha) 青井 貴之  神戸大学, 科学技術イノベーション研究科, 教授 (00546997)
Project Period (FY) 2019-06-28 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywords一酸化炭素 / 細胞分化 / ポルフィリン / シクロデキストリン / ヘム / ヘムオキシゲナーゼ / ガスバイオロジー / ヘモグロビン / ガス状シグナル伝達物質 / iPS細胞
Outline of Research at the Start

細胞内では一酸化炭素がシグナル伝達物質として機能することが注目されているが,その研究手段は乏しい。本研究では細胞内一酸化炭素を定量,追加および除去できる分子ツールを用いて,細胞分化プロセスにおける一酸化炭素の生理的役割について考察する。細胞分化の分子レベルでの本質的機構解明に貢献する。

Outline of Final Research Achievements

In this study, to understand the physiological function of carbon monoxide as an intracellular signal molecule, we investigated utilization of the artificial hemoglobin model complex, hemoCD. hemoCD is a supramolecular complex functions as an in vivo CO scavenger. First, the function of hemoCD on cells was examined. As a result, we have established an assay that accurately quantifies intracellular CO using hemoCD. This assay could also be applied to quantify CO in animal tissues, which has filed a patent application. Using this assay, the pharmacokinetics of CO was clarified. Intracellular CO knockdown by a system combining hemoCD and a cell-permeable peptide (R8-hemoCD), development of CORM401-E, a CO-releasing molecule with improved cell-permeability, a heme derivative that does not emit CO when decomposed intracellularly, have been succeeded in developing a group of chemical tools that can be used to elucidate the physiological function of intracellular CO.

Academic Significance and Societal Importance of the Research Achievements

本研究は有毒ガスでありながら生体内シグナルメディエーターとして機能する一酸化炭素の生理作用について,より深く理解するためのものである。細胞内では様々なシグナル伝達物質により情報が伝達され,細胞分化などの生命が活動するために必要なプロセスを実施している。本研究では(1) 細胞内一酸化炭素を除去する方法,(2)細胞および生体組織内に分布した一酸化炭素を簡単に定量する方法,(3)細胞内に一酸化炭素を効率よくデリバリーする化合物,(4)細胞内で分解されるが一酸化炭素を発しないヘム誘導体などを開発することに成功した。これらの成果は一酸化炭素の生理作用に対する深い理解をもたらすものである。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (16 results)

All 2021 2020 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (7 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] INSERM(フランス)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Functional Myoglobin Model Composed of a Strapped Porphyrin/Cyclodextrin Supramolecular Complex with an Overhanging COOH That Increases O<sub>2</sub>/CO Binding Selectivity in Aqueous Solution2021

    • Author(s)
      Mao Qiyue、Das Pradip K.、Le Gac St?phane、Boitrel Bernard、Dorcet Vincent、Oohora Koji、Hayashi Takashi、Kitagishi Hiroaki
    • Journal Title

      Inorganic Chemistry

      Volume: 60 Issue: 16 Pages: 12392-12404

    • DOI

      10.1021/acs.inorgchem.1c01628

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] FRET‐Based In‐Cell Detection of Highly Selective Supramolecular Complexes of <i>meso</i> ‐Tetraarylporphyrin with Peptide/BODIPY‐Modified Per‐ <i>O</i> ‐Methyl‐β‐Cyclodextrins2021

    • Author(s)
      Nakagami Atsuki、Mao Qiyue、Gouhier G?raldine、Arima Hidetoshi、Kitagishi Hiroaki
    • Journal Title

      ChemBioChem

      Volume: 22 Issue: 22 Pages: 3190-3198

    • DOI

      10.1002/cbic.202100380

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Capture of carbon monoxide using a heme protein model: from biomimetic chemistry of heme proteins to physiological and therapeutic applications2021

    • Author(s)
      Kitagishi Hiroaki、Mao Qiyue
    • Journal Title

      Polymer Journal

      Volume: 54 Issue: 4 Pages: 465-472

    • DOI

      10.1038/s41428-021-00591-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sensitive quantification of carbon monoxide in vivo?reveals a protective role of circulating hemoglobin in CO?intoxication2021

    • Author(s)
      Mao Qiyue、Kawaguchi Akira T.、Mizobata Shun、Motterlini Roberto、Foresti Roberta、Kitagishi Hiroaki
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 425-425

    • DOI

      10.1038/s42003-021-01880-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Synthetic heme protein models that function in aqueous solution2021

    • Author(s)
      Kitagishi Hiroaki、Kano Koji
    • Journal Title

      Chemical Communications

      Volume: 57 Issue: 2 Pages: 148-173

    • DOI

      10.1039/d0cc07044k

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intracellular Delivery of Adamantane-tagged Small Molecule, Proteins, and Liposomes Using an Octaarginine-conjugated β-Cyclodextrin2020

    • Author(s)
      H. Kitagishi, M. Jiromaru, N. Hasegawa
    • Journal Title

      ACS Applied Bio Materials

      Volume: - Issue: 8 Pages: 4902-4911

    • DOI

      10.1021/acsabm.0c00421

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Sensitive and selective quantification of carbon monoxide (CO) distributed in vivo by an iron(II)porphyrin-cyclodextrin supramolecular complex2021

    • Author(s)
      Qiyue Mao, Hiroaki Kitagishi
    • Organizer
      Pacifichem 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Synthetic Analogs of Heme Proteins in Water2021

    • Author(s)
      Hiroaki Kitagishi
    • Organizer
      Pacifichem 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Detection and removal of carbon monoxide (CO) in vivo using a highly selective and sensitive CO-scavenger, hemoCD2021

    • Author(s)
      Hiroaki Kitagishi
    • Organizer
      Pacifichem 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヘムとCO;化学的見地からの理解と展望2021

    • Author(s)
      北岸 宏亮
    • Organizer
      第19回新生児黄疸管理研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 超分子ヘモグロビンモデル錯体のin vivoにおけるガス結合物質としての応用展開2021

    • Author(s)
      北岸 宏亮,毛 斉悦
    • Organizer
      第70回高分子討論会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Biomedical Application of Iron(II)porphyrin-Cyclodextrin Supramolecular Complexes Working as Artificial Hemoglobin In Vivo2021

    • Author(s)
      Hiroaki Kitagishi
    • Organizer
      Waiting for 20th International Cyclodextrin Symposium, Bridge Virtual Meeting
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Removal and quantification of biological CO in mammals using a synthetic heme protein model compound.2021

    • Author(s)
      Qiyue Mao, Hiroaki Kitagishi
    • Organizer
      日本化学会第101春季年会, 2021年3月, オンライン開催
    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] 解毒剤及び解毒剤用キット2021

    • Inventor(s)
      北岸宏亮,毛斉悦
    • Industrial Property Rights Holder
      北岸宏亮,毛斉悦
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 一酸化炭素の定量方法2020

    • Inventor(s)
      北岸 宏亮,毛 斉悦
    • Industrial Property Rights Holder
      北岸 宏亮,毛 斉悦
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-010710
    • Filing Date
      2020
    • Related Report
      2019 Research-status Report

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Published: 2019-07-04   Modified: 2023-01-30  

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