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Analysis of carbon monoxide toxicity using water-soluble CORMs

Research Project

Project/Area Number 17H04147
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Legal medicine
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Aki Toshihiko  東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (60304474)

Co-Investigator(Kenkyū-buntansha) 鵜沼 香奈  東京医科歯科大学, 大学院医歯学総合研究科, 講師 (30586425)
船越 丈司  東京医科歯科大学, 大学院医歯学総合研究科, 助教 (40444715)
則竹 香菜子  東京医科歯科大学, 大学院医歯学総合研究科, 特任助教 (40758067)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords一酸化炭素 / CORM-3 / フィブロネクチン / p62 / 硫化水素 / メタボロミクス / プロテオミクス / ミトコンドリア / タンパク質凝集体 / ヘム / プロテオーム / 法医病理
Outline of Final Research Achievements

Carbon monoxide is a toxic gas, due to its high affinity to heme and resultant inhibition of binding of oxygen to heme. On the other side, carbon monoxide is generated in human body and has protective roles against stresses. Water soluble carbon monoxide releasing molecules (CORMs) has been attracted much attention due to its easy use for experiments. We found that exposure of a high concentration of CORM-3 to cells resulted in the aggregation of p62 as well as fibronectin. Since these two molecules are essential to autophagy as well as formation of extracellular matrix, CORM-3 should impairs these processes when applied to cells at high concentrations.

Academic Significance and Societal Importance of the Research Achievements

一酸化炭素は近年、その毒性よりむしろ低濃度における細胞・臓器保護作用が注目を集め、各種一酸化炭素発生剤が開発されてきた。その中でも水溶性一酸化炭素発生剤であるCORM-A1, CORM-3はその実用性から注目を集めている。本研究で、CORM-3には高濃度で用いた場合にある特定のタンパク質に凝集体形成を誘導する作用があることが判明し、水溶性一酸化炭素発生剤の適正な使用法への一助になったものと考えられる。

Report

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

    (14 results)

All 2019 2018 2017

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 5 results) Presentation (4 results) (of which Int'l Joint Research: 1 results) Book (2 results)

  • [Journal Article] Increased circulating peroxiredoxin-4 in sepsis model rats involves secretion from hepatocytes and is mitigated by GYY41372019

    • Author(s)
      Unuma Kana、Yoshikawa Ayaka、Aki Toshihiko、Uemura Koichi
    • Journal Title

      Journal of Toxicologic Pathology

      Volume: 32 Issue: 4 Pages: 305-310

    • DOI

      10.1293/tox.2019-0030

    • NAID

      130007731846

    • ISSN
      0914-9198, 1881-915X
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Formation of high molecular weight p62 by CORM-32019

    • Author(s)
      Aki Toshihiko、Unuma Kana、Noritake Kanako、Hirayama Naho、Funakoshi Takeshi、Uemura Koichi
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 1 Pages: e0210474-e0210474

    • DOI

      10.1371/journal.pone.0210474

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hydrogen sulfide donor NaHS causes bronchitis with enhanced respiratory secretion in rats2019

    • Author(s)
      Unuma Kana、Aki Toshihiko、Yamashita Ayaka、Yoshikawa Ayaka、Uemura Koichi
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 44 Issue: 2 Pages: 107-112

    • DOI

      10.2131/jts.44.107

    • NAID

      130007590450

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interaction of carbon monoxide-releasing ruthenium carbonyl CORM-3 with plasma fibronectin2018

    • Author(s)
      Aki Toshihiko、Unuma Kana、Noritake Kanako、Kurahashi Hatsumi、Funakoshi Takeshi、Uemura Koichi
    • Journal Title

      Toxicology in Vitro

      Volume: 50 Pages: 201-209

    • DOI

      10.1016/j.tiv.2018.03.010

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The down-regulation of cardiac contractile proteins underlies myocardial depression during sepsis and is mitigated by carbon monoxide2018

    • Author(s)
      Unuma Kana、Aki Toshihiko、Nagano Suguru、Watanabe Ryo、Uemura Koichi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 495 Issue: 2 Pages: 1668-1674

    • DOI

      10.1016/j.bbrc.2017.12.020

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Necrosis in human neuronal cells exposed to paraquat2018

    • Author(s)
      Naho Hirayama, Toshihiko Aki, Takeshi Funakoshi, Kanako Noritake, Kana Unuma, Koichi Uemura.
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 43 Issue: 3 Pages: 193-202

    • DOI

      10.2131/jts.43.193

    • NAID

      130006507321

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Emerging roles of mitochondria and autophagy in liver injury during sepsis2017

    • Author(s)
      Aki Toshihiko、Unuma Kana、Uemura Koichi
    • Journal Title

      Cell Stress

      Volume: 1 Issue: 2 Pages: 79-89

    • DOI

      10.15698/cst2017.11.110

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Restoration of YAP activation rescues HL-1 cardiomyocytes from apoptotic death by ethanol2017

    • Author(s)
      Kanako Noritake, Toshihiko Aki, Moe Kimura, Takeshi Funakoshi, Kana Unuma, Koichi Uemura.
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 42 Issue: 5 Pages: 545-551

    • DOI

      10.2131/jts.42.545

    • NAID

      130006076729

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 敗血症性肝障害に対する硫化水素の影響2019

    • Author(s)
      鵜沼香奈、秋利彦、吉川綾香、上村公一
    • Organizer
      第103 次日本法医学会学術全国集会、 仙台
    • Related Report
      2019 Annual Research Report
  • [Presentation] Down-regulation of cardiac contractile protein is involved in cardiac dysfunction during sepsis and is mitigated by carbon monoxide.2018

    • Author(s)
      Kana Unuma, Toshihiko Aki, Ryo Watanabe, Koichi Uemura
    • Organizer
      IALM 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経細胞SH-SY5Yにおけるパラコート曝露による細胞死とそのメカニズムの検討2017

    • Author(s)
      平山菜穂、秋利彦、上村公一
    • Organizer
      第86回日本法医学会学術関東地方集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] エタノールによる心筋細胞死は YAP 活性化により抑制される2017

    • Author(s)
      則竹香菜子, 秋 利彦, 上村公一
    • Organizer
      第52回 日本アルコール・アディクション医学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Book] Autophagy in health and disease2018

    • Author(s)
      Toshihiko Aki, Kanako Noritake, Kana Unuma, Koichi Uemura
    • Total Pages
      18
    • Publisher
      Humana press
    • ISBN
      9783319981451
    • Related Report
      2018 Annual Research Report
  • [Book] Comprehensive Toxicology 3rd ed Volume 1 (General subjects).2018

    • Author(s)
      Toshihiko Aki, Kanako Noritake, Takeshi Funakoshi, Koichi Uemura.
    • Total Pages
      25
    • Publisher
      Elsevier
    • ISBN
      9780081006016
    • Related Report
      2017 Annual Research Report

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

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