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The role of cellular redox system in inflammatory disorders of acute lung injury

Research Project

Project/Area Number 15K10551
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Anesthesiology
Research InstitutionThe Tazuke Kofukai

Principal Investigator

ADACHI Takehiko  公益財団法人田附興風会, 医学研究所 第9研究部, 部長 (90252428)

Co-Investigator(Kenkyū-buntansha) 広田 喜一  関西医科大学, 医学部, 教授 (00283606)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords酸素環境 / 敗血症 / 急性肺障害 / thioredoxin / TXNIP / HIF-1 / 低酸素誘導性因子1 / 急性肺傷害
Outline of Final Research Achievements

The aim of this study is to evaluate the clinical significance of the cellular redox system consisting of thioredoxin and thioredoxin interacting protein (Txnip) for the protection against inflammatory disorders including septi shock, ALI, and ARDS. Since inflammation has been associated with hypoxia and the resulting dysregulation of oxygen homeostasis, we investigated the functional interaction between the thioredoxin system and hypoxia-inducible factor 1 (HIF-1) under inflammatory conditions. We showed that thioredoxin enhanced the transcriptional activity of HIF-1. Thioredoxin-induced HIF-1 activation up-regulated the expression level of Txnip, which could, in turn, suppress the function of thioredoxin. These results revealed that the cellular redox environment was maintained by a subtle balance and interplay between these redox-related molecules.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report

Research Products

(9 results)

All 2018 2017 2016 2015

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 7 results,  Acknowledgement Compliant: 5 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Propofol induces a metabolic switch to glycolysis and cell death in a mitochondrial electron transport chain-dependent manner2018

    • Author(s)
      Sumi Chisato、Okamoto Akihisa、Tanaka Hiromasa、Nishi Kenichiro、Kusunoki Munenori、Shoji Tomohiro、Uba Takeo、Matsuo Yoshiyuki、Adachi Takehiko、Hayashi Jun-Ichi、Takenaga Keizo、Hirota Kiichi
    • Journal Title

      PLoS One

      Volume: 13

    • DOI

      10.1371/journal.pone.0192796

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] VHL-deficient renal cancer cells gain resistance to mitochondria-activating apoptosis inducers by activating AKT through the IGF1R-PI3K pathway2017

    • Author(s)
      Yamaguchi R, Harada H, Hirota K
    • Journal Title

      Tumour Biol

      Volume: 37 Pages: 13295-13306

    • DOI

      10.1007/s13277-016-5260-2

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cigarette smoke reversibly activates hypoxia-inducible factor 1 in a reactive oxygen species-dependent manner2016

    • Author(s)
      Daijo H, Hoshino Y, Kai S, Suzuki K, Nishi K, Matsuo Y, Harada H, Hirota K
    • Journal Title

      Sci Rep

      Volume: 6 Pages: 34424-34424

    • DOI

      10.1038/srep34424

    • NAID

      120005850269

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The antioxidant N-acetyl cysteine suppresses lidocaine-induced intracellular reactive oxygen species production and cell death in neuronal SH-SY5Y cells2016

    • Author(s)
      Okamoto A, Tanaka M, Sumi C, Oku K, Kusunoki M, Nishi K, Matsuo Y, Takenaga K, Shingu K, Hirota K
    • Journal Title

      BMC anesthesiology

      Volume: 16 Pages: 104-104

    • DOI

      10.1186/s12871-016-0273-3

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1alpha2015

    • Author(s)
      Goto Y, Zeng L, YeomCJ, Zhu Y, Morinibu A, Shinoyam K, Kobayashi M, Hirota K, Itasaka S, Yoshimura M, Tanimoto K, Sowa T, Menju T, Sonobe M, Kakeya H, Toi M, Date H, Hammond EM, Hiraoka M, Harada H.
    • Journal Title

      Nature communication

      Volume: 6 Pages: 1-10

    • DOI

      10.1038/ncomms7153

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Involvement of hypozia-inducible factors in the dysregulation of oxygen homeostasis in sepsis2015

    • Author(s)
      Hirota K.
    • Journal Title

      Cardiovascular & hematological disorders drug targets.

      Volume: 15 Pages: 29-40

    • DOI

      10.2174/1871529x15666150108115553

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Volatile anesthetics suppress glucose-stimulated insulin secretion in MIN6 cells by inhibiting glucose-induced activation of hypoxia-inducible factor 1.2015

    • Author(s)
      Suzuki K, Sato Y, Kai S, Nishi K, Adachi T, Matsuo Y, Hirota K.
    • Journal Title

      Peer J.

      Volume: 3 Pages: 1498-1498

    • DOI

      10.7717/peerj.1498

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] HIF-1-Mediated Suppression of Mitochondria Electron Transport Chain Function Confers _Resistance to Lidocaine-induced Cell Death2017

    • Author(s)
      SHINICHI KAI, Kiichi Hirota, Chisato Sumi, Akihisa Okamoto, Kenichiro Nishi, Munenori Kusunoki, Yoshiyuki Matsuo, Takehiko Adachi
    • Organizer
      American Society of Anesthesiology 2017 annual meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] transmitochondrial cybrids細胞を用いたプロポフォール細胞毒性の検討-プロポフォール注入症候群の病態生理学2016

    • Author(s)
      広田 喜一, 角 千里, 楠 宗矩, 岡本 明久 田中 宏昌, 西 憲一郎 , 松尾 禎之
    • Organizer
      第23回日本静脈麻酔学会
    • Place of Presentation
      コラッセふくしま(福島市)
    • Related Report
      2016 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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