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Study on the role of endogenous CO in the circadian clock system

Research Project

Project/Area Number 17H02208
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomolecular chemistry
Research InstitutionDoshisha University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) 佐上 郁子  京都府立大学, 生命環境科学研究科, 研究員 (10143033)
根木 滋  同志社女子大学, 薬学部, 准教授 (50378866)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2017: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords一酸化炭素 / 体内時計 / 概日リズム / ヘム / 炎症 / 時計遺伝子 / シクロデキストリン / サーガディアンリズム / 超分子錯体 / ガスバイオロジー
Outline of Final Research Achievements

In this study, we investigated the effect of endogenous CO depletion on the circadian clock system using highly selective CO scavenging molecule, hemoCD. Upon injection of hemoCD to mice, the expression levels of clock genes such as Per and Cry were significantly disrupted as a result of CO-depletion. The mechanistic study revealed the activity changes of CO-responsive transcriptional factors, CLOCK and NPAS2. In addition, CO-removal-induced inflammatory responses also caused the disruption of the clock genes. Our study clearly demonstrates, for the first time, that the depletion of endogenous CO induces disruption of circadian clock system. The further mechanistic study is ongoing in our laboratory.

Academic Significance and Societal Importance of the Research Achievements

有毒ガスとして知られる一酸化炭素が体内時計の調節に不可欠な存在であるという直接的な実験的証拠が得られた。学術的にガスバイオロジーの研究成果として意義深いとともに,体内時計の乱れは様々な疾病を引き起こすことが知られているが,そのメカニズム解明の一端を明らかにした研究成果である。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (27 results)

All 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (14 results) (of which Int'l Joint Research: 3 results,  Invited: 10 results) Patent(Industrial Property Rights) (4 results)

  • [Int'l Joint Research] パリ第12大学/ストラスブール大学/レンヌ大学(フランス)

    • Related Report
      2019 Annual Research Report
  • [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 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modelling haemoproteins: porphyrins and cyclodextrins as sources of inspiration2019

    • Author(s)
      Vonesch Maxime、Wytko Jennifer A.、Kitagishi Hiroaki、Kano Koji、Weiss Jean
    • Journal Title

      Chemical Communications

      Volume: 55 Issue: 97 Pages: 14558-14565

    • DOI

      10.1039/c9cc07545c

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Supramolecular Complexation in Biological Media: NMR Study on Inclusion of an Anionic Tetraarylporphyrin into a Per‐ O ‐Methylated β‐Cyclodextrin Cavity in Serum, Blood, and Urine2019

    • Author(s)
      Kitagishi Hiroaki、Saito Mai、Mao Qiyue、Kiriyama Akiko、Negi Shigeru、Kano Koji
    • Journal Title

      Chemistry An Asian Journal

      Volume: 14 Issue: 19 Pages: 3320-3328

    • DOI

      10.1002/asia.201900983

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Design and Biological Evaluation of Manganese- and Ruthenium-based Hybrid CO-RMs (HYCOs)2019

    • Author(s)
      A. Ollivier, R. Foresti, Z. El Ali, T. Martens, H. Kitagishi, R. Motterlini, M. Rivard
    • Journal Title

      ChemMedChem

      Volume: 14 Issue: 18 Pages: 1684-1691

    • DOI

      10.1002/cmdc.201900426

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Circadian clock disruption by selective removal of endogenous carbon monoxide2018

    • Author(s)
      Minegishi Saika、Sagami Ikuko、Negi Shigeru、Kano Koji、Kitagishi Hiroaki
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 11996-11996

    • DOI

      10.1038/s41598-018-30425-6

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optimized synthesis of a per-O-methylated β-cyclodextrin dimer linked at the secondary face by a pyridine ligand2018

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

      Journal of Inclusion Phenomena and Macrocyclic Chemistry

      Volume: 93 Issue: 1-2 Pages: 67-76

    • DOI

      10.1007/s10847-018-0839-4

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PEGylated carboxyhemoglobin bovine (SANGUINATE) ameliorates myocardial infarction in a rat model2018

    • Author(s)
      Kawaguchi Akira T.、Salybekov Amankeldi A.、Yamano Mariko、Kitagishi Hiroaki、Sekine Kaori、Tamaki Tetsuro
    • Journal Title

      Artificial Organs

      Volume: 42 Issue: 12 Pages: 1174-1184

    • DOI

      10.1111/aor.13384

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Carbon monoxide?induced metabolic switch in adipocytes improves insulin resistance in obese mice2018

    • Author(s)
      Braud Laura、Pini Maria、Muchova Lucie、Manin Sylvie、Kitagishi Hiroaki、Sawaki Daigo、Czibik Gabor、Ternacle Julien、Derumeaux Genevi?ve、Foresti Roberta、Motterlini Roberto
    • Journal Title

      JCI Insight

      Volume: 3 Issue: 22

    • DOI

      10.1172/jci.insight.123485

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Biological roles of endogenous carbon monoxide in blood2020

    • Author(s)
      H. Kitagishi
    • Organizer
      The 17th International Symposium on Blood Substitutes and Oxygen Therapeutics
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Supramolecular porphyrin-cyclodextrin complexes as the versatile biomimetic chemical compounds2018

    • Author(s)
      Hiroaki Kitagishi
    • Organizer
      Supramolecular Chemistry of Nitrogen Ligands
    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 生体内一酸化炭素の擬ノックダウン法による機能解明2018

    • Author(s)
      北岸 宏亮
    • Organizer
      第6回バイオ関連シンポジウム若手フォーラム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 生体内COの除去による体内時計の変化2018

    • Author(s)
      北岸 宏亮,峯岸 彩夏, 佐上 郁子,根木 滋,加納 航治
    • Organizer
      第12回バイオ関連化学シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 生体内一酸化炭素の選択的除去が及ぼす体内時計システムへの影響2018

    • Author(s)
      北岸 宏亮,峯岸 彩夏, 佐上 郁子,根木 滋,加納 航治
    • Organizer
      第25回日本血液代替物学会年次大会
    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
  • [Presentation] Detection and removal of endogenous CO in vitro and in vivo by an aqueous hemoprotein model complex2018

    • Author(s)
      Hiroaki Kitagishi
    • Organizer
      10th International Conference on Heme Oxygenase 2018
    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生体で機能するヘムタンパク質モデル としてのメチル化シクロデキストリン/ 鉄ポルフィリン包接錯体2018

    • Author(s)
      北岸 宏亮
    • Organizer
      第12回多糖の未来フォーラム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 高親和性分子間相互作用がもたらす“擬ノックダウン法”の提案2018

    • Author(s)
      北岸 宏亮
    • Organizer
      第3回先端ケミカルバイオロジー研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 生命研究に役立つ ヘムタンパク質ミメティック錯体2018

    • Author(s)
      北岸 宏亮
    • Organizer
      第31回生物無機化学夏季セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 生体内一酸化炭素の擬ノックダウン法による機能解明2018

    • Author(s)
      北岸 宏亮
    • Organizer
      第6回バイオ関連シンポジウム若手フォーラム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 生体内COの除去による体内時計の変化2018

    • Author(s)
      北岸 宏亮,峯岸 彩夏, 佐上 郁子,根木 滋,加納 航治
    • Organizer
      第6回バイオ関連シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 生体で機能するヘムタンパク質モデルとしてのメチル化シクロデキストリン/鉄ポルフィリン包接錯体2018

    • Author(s)
      北岸 宏亮
    • Organizer
      第12回多糖の未来フォーラム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 高親和性分子間相互作用がもたらす“擬ノックダウン法”の提案2018

    • Author(s)
      北岸 宏亮
    • Organizer
      第3回先端ケミカルバイオロジー研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 生命研究に役立つヘムタンパク質ミメティック錯体2018

    • Author(s)
      北岸 宏亮
    • Organizer
      第31回生物無機化学夏季セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [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
      同志社大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-010710
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 新規化合物、炎症性疾患の予防及び/又は治療のための薬剤、又は、一酸化炭素送達物質2019

    • Inventor(s)
      北岸 宏亮,高山 実花子, R. Motterlini
    • Industrial Property Rights Holder
      同志社大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-040610
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 新規化合物、炎症性疾患の予防及び/又は治療のための薬剤、又 は、一酸化炭素送達物質2019

    • Inventor(s)
      同志社大学
    • Industrial Property Rights Holder
      同志社大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 新規化合物、炎症性疾患の予防及び/又は治療のための薬剤、又は、一酸化炭素送達物質2019

    • Inventor(s)
      同志社大学
    • Industrial Property Rights Holder
      同志社大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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