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Mechanistic study on circadian clock system regulated by heme/CO crosstalk

Research Project

Project/Area Number 20H02871
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
Research InstitutionDoshisha University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) 廣田 毅  名古屋大学, トランスフォーマティブ生命分子研究所, 特任准教授 (50372412)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2021: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2020: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords一酸化炭素 / ヘモグロビン / シクロデキストリン / ポルフィリン / ヘム / サーカディアンリズム / 概日リズム / ヘムオキシゲナーゼ / ガス状シグナル伝達物質 / 時計遺伝子 / ケミカルツール
Outline of Research at the Start

細胞内には約24時間周期で遺伝子発現のリズムが刻まれており,その制御にはヘムやCOといった生体内小分子が関与していると考えられているが,その詳細は明らかではない。本研究では従来の遺伝子工学的手法では制御が困難なヘムおよびCOに対して,これらの動態をコントロールすることのできるケミカルツール群を開発して活用することにより,ヘムとCOがクロストークする概日リズム制御機構の一端を明らかにすることを目的とする。

Outline of Final Research Achievements

In this study, to reveal the biological function of endogenous CO, we investigated in vitro and in vivo on CO using artificial hemoglobin "hemoCD" that was originally developed in our laboratory. In this year, we have developed our hemoCDs as a selective CO and HCN scavenger in vivo. This system has been applicable for fire-gas antidote. The results have been published in PNAS. According to this publication, the research was press-released and seen by many media.

Academic Significance and Societal Importance of the Research Achievements

我々は独自に人工ヘモグロビン化合物hemoCDを開発し,それを体内に導入することで生体内COを選択的に除去するシステムを構築した。この系は生体内における概日リズムに代表されるような様々な生理現象について,COの関与を明らかにできる。それだけでなく火災などで頻発するCO中毒の解毒剤としても利用できる道を見出して,研究をすすめて成果を一般に公表することに至った。これまでにないCO中毒解毒剤の開発は,多くの人命救助につながることが期待され,その社会的意義は大きいと考えられる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (38 results)

All 2023 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 4 results) Presentation (24 results) (of which Int'l Joint Research: 7 results,  Invited: 8 results) Patent(Industrial Property Rights) (2 results)

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

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Spontaneous reduction of iron(iii)porphyrin to iron(ii)porphyrin-CO complex in mouse circulation2023

    • Author(s)
      Noguchi Masataka、Mao Qiyue、Nakagami Atsuki、Kitagishi Hiroaki
    • Journal Title

      Chemical Communications

      Volume: - Issue: 41 Pages: 6211-6214

    • DOI

      10.1039/d3cc00420a

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of carbon monoxide-releasing molecules conjugated to polysaccharides (glyco-CORMs) for delivering CO during obesity2023

    • Author(s)
      Mohan Shruti、Barel Louis-Antoine、Benrahla Djamal Eddine、Do Bernard、Mao Qiyue、Kitagishi Hiroaki、Rivard Michael、Motterlini Roberto、Foresti Roberta
    • Journal Title

      Pharmacological Research

      Volume: 191 Pages: 106770-106770

    • DOI

      10.1016/j.phrs.2023.106770

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Inclusion Complex Formation with Tetra‐PEGylated Tetraphenylporphyrin and Face‐to‐Face Cyclodextrin Dimer through Unprecedented Molecular Threading2023

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

      Chemistry A European Journal

      Volume: - Issue: 32

    • DOI

      10.1002/chem.202300408

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A synthetic porphyrin as an effective dual antidote against carbon monoxide and cyanide poisoning2023

    • Author(s)
      Mao Qiyue、Zhao Xuansu、Kiriyama Akiko、Negi Shigeru、Fukuda Yasutaka、Yoshioka Hideki、Kawaguchi Akira T.、Motterlini Roberto、Foresti Roberta、Kitagishi Hiroaki
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 120 Issue: 9 Pages: 1-10

    • DOI

      10.1073/pnas.2209924120

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of Charged-cluster Distribution of the ZIF268 Zinc Finger Surface on Cell Membrane Permeability2023

    • Author(s)
      Negi Shigeru、Hamori Mami、Kawahara-Nakagawa Yuka、Mashimo Masato、Imanishi Miki、Kuki Nozomi、Kawahito Yuri、Manabe Takayuki、Kawamura Nobuyuki、Yasukawa Jyunichiro、Kitagishi Hiroaki、Sugiura Yukio
    • Journal Title

      Chemistry Letters

      Volume: 52 Issue: 2 Pages: 75-78

    • DOI

      10.1246/cl.220464

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Monolayer Formation and Chiral Recognition of Binaphthyl Amphiphiles at the Air?Water Interface2023

    • Author(s)
      Negi Shigeru、Hamori Mami、Kubo Yoshiyasu、Kitagishi Hiroaki、Kano Koji
    • Journal Title

      Bulletin of the Chemical Society of Japan

      Volume: 96 Issue: 1 Pages: 48-56

    • DOI

      10.1246/bcsj.20220286

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [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 Annual Research 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 Annual Research Report
    • Peer Reviewed
  • [Presentation] COとHCN同時ガス中毒に対する人工ヘモグロビンモデル錯体の解毒有効性の評価2022

    • Author(s)
      毛 斉悦、北岸 宏亮
    • Organizer
      第29回日本血液代替物学会年次大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Capture of Carbon Monoxide and Cyanide In Vivo Using Synthetic Hemoglobin Model Complexes2022

    • Author(s)
      Hiroaki Kitagishi, Qiyue Mao
    • Organizer
      10th Asian Biological Inorganic Conference
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] High affinity threading of porphyrin having polymer arms through a methylated cyclodextrin dimer2022

    • Author(s)
      Qiyue Mao, Hiroaki Kitagishi
    • Organizer
      10th Asian Biological Inorganic Conference
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] シクロデキストリンを使った人工ヘモグロビンの合成とそれを用いた創薬チャレンジ2022

    • Author(s)
      北岸 宏亮
    • Organizer
      第19回糖鎖科学コンソーシアムシンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 有機化学から生体機能解明への挑戦2022

    • Author(s)
      北岸 宏亮
    • Organizer
      日本化学会ディビジョン講演会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] ヘモグロビン・バイオミメティック錯体を利用した火災ガス中毒治療薬の開発2022

    • Author(s)
      北岸 宏亮, 毛 斉悦
    • Organizer
      メタルバイオサイエンス研究会2022
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Selective Depletion of Endogenous CO In Vitro and In Vivo by Hemoprotein Biomimetic Model Complexes2022

    • Author(s)
      Hiroaki Kitagishi
    • Organizer
      Gordon Research Conference (Chemistry and Biology of Tetrapyrroles)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 火災ガス中毒を治療する人工ヘモグロビン化合物2022

    • Author(s)
      北岸 宏亮
    • Organizer
      日本中毒学会西日本地方会
    • Related Report
      2021 Annual Research Report
  • [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
  • [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] Intracellular delivery of small molecules, proteins, and liposomes using cell-penetrating cyclodextrins2021

    • Author(s)
      Hiroaki Kitagishi
    • Organizer
      Pacifichem 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ポルフィリン鉄錯体とシクロデキストリン二量体から構成される人工ヘモグロビンの構築と生体内ガスの吸着試薬としての利用2021

    • Author(s)
      北岸 宏亮, 毛 斉悦
    • Organizer
      第28回日本血液代替物学会年次大会
    • Related Report
      2021 Annual Research Report
  • [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] 人工ヘモグロビンモデル錯体による生体内一酸化炭素の定量および除去2021

    • Author(s)
      北岸 宏亮,毛 斉悦
    • Organizer
      第18回ホストーゲスト・超分子化学シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] 分子Tシャツ:PEG鎖を有するテトラアリールポルフィリンとメチル化シクロデキストリン二量体との不可逆的な包接錯体形成2021

    • Author(s)
      毛 斉悦, 松下 麟太郎, 北岸 宏亮
    • Organizer
      第18回ホストーゲスト・超分子化学シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] マレイミド基を側鎖に有するhemoCDによる動物体内COの選択的除去2021

    • Author(s)
      野口大貴, 毛斉悦, 北岸宏亮
    • Organizer
      第37回シクロデキストリンシンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] ピリジンストラップポルフィリン鉄錯体と銅錯体をリンカーに有するシクロデキストリン二量体を用いたシトクロムcオキシダーゼモデル錯体2021

    • Author(s)
      北口 文都, 毛 斉悦, 北岸 宏亮
    • Organizer
      第37回シクロデキストリンシンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] 水中オレフィンメタセシス反応を利用したシクロデキストリン/ポルフィリン超分子カテナン錯体の形成2021

    • Author(s)
      浅井 薫、毛 斉悦、北岸 宏亮
    • Organizer
      第37回シクロデキストリンシンポジウム
    • Related Report
      2021 Annual Research Report
  • [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 Annual Research Report
  • [Presentation] マレイミド修飾hemoCDの投与による動物体内COの選択的除去2021

    • Author(s)
      野口大貴,毛 斉悦,北岸宏亮
    • 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 Annual Research Report
  • [Presentation] ピリジン配位子をストラップ部位に組み込んだ水溶性ポルフィリンの合成とそのメチル化シクロデキストリン超分子錯体2021

    • Author(s)
      北口文都, 毛 斉悦, 北岸宏亮
    • 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 Annual Research Report
  • [Patent(Industrial Property Rights)] 一酸化炭素の定量方法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)] 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

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Published: 2020-04-28   Modified: 2024-01-30  

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