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Investigation for establishment for a novel intervention to protect kidney against hypoxic injury by inducing metabolic reprogramming by manipulating the transcription factor HIF-1 activity

Research Project

Project/Area Number 24659695
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Anesthesiology/Resuscitation studies
Research InstitutionKansai Medical University (2013)
Kyoto University (2012)

Principal Investigator

HIROTA Kiichi  関西医科大学, 医学部, 准教授 (00283606)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords低酸素 / 腎臓 / HIF-1 / 代謝 / リプログラミング / 保護 / 解糖
Research Abstract

In order to established a novel method to protect kidney from ischemic injury, we explored an intervention by manipulate the transcription factor HIF-1 activity with the small molecular compound n-propyl gallate (nPG). We demonstrated that forced activation of hypoxia-inducible factor 1(HIF-1) by the exogenous small molecule n-propyl gallate (nPG) induced metabolic reprograming from cellular energy generation dependent on OXPHOS in mitochondria to glycolysis-dominant one in the primary cultured tubular and glomerular cells. Moreover, we indicated that nPG pretreatment induced HIF-1 activation and expression of glycolytic enzymes and conferred tolerance against hypoxia-induced cell death of cells derived from kidney.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report

Research Products

(41 results)

All 2014 2013 2012 Other

All Journal Article (25 results) (of which Peer Reviewed: 21 results) Presentation (16 results) (of which Invited: 4 results)

  • [Journal Article] 肺胞低酸素と炎症-低酸素誘導性因子活性化の視点から-2014

    • Author(s)
      広田喜一
    • Journal Title

      分子呼吸器病

      Volume: 18 Pages: 73-5

    • Related Report
      2013 Final Research Report
  • [Journal Article] 肺内酸素環境と肺疾患-低酸素-HIF-炎症-2014

    • Author(s)
      広田喜一
    • Journal Title

      呼吸器内科

      Volume: 25 Pages: 270-5

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Macrophage migration inhibitory factor diminishes muscle glucose transport induced by insulin and AICAR in a muscle type-dependent manner2014

    • Author(s)
      Miyatake S, Manabe Y, Inagaki A, Furuichi Y, Takagi M, Taoka M, Isobe T, Hirota K, Fujii NL
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 444 Pages: 496-501

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The volatile anesthetic isoflurane differentially suppresses the induction of erythropoietin synthesis elicited by acute anemia and systemic hypoxemia in mice in an hypoxia-inducible factor-2-dependent manner2014

    • Author(s)
      Kai S, Tanaka T, Matsuyama T, Suzuki K, Hirota K
    • Journal Title

      Eur J Pharmacol

      Volume: 732C Pages: 43-9

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 肺内酸素環境と肺疾患 -低酸素-HIF-炎症-2014

    • Author(s)
      広田喜一
    • Journal Title

      呼吸器内科

      Volume: 25 Pages: 270-275

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 肺胞低酸素と炎症 -低酸素誘導性因子活性化の視点から-2014

    • Author(s)
      広田喜一
    • Journal Title

      分子呼吸器病

      Volume: 18 Pages: 73-75

    • Related Report
      2013 Annual Research Report
  • [Journal Article] The volatile anesthetic isoflurane differentially suppresses the induction of erythropoietin synthesis elicited by acute anemia and systemic hypoxemia in mice in an hypoxia-inducible factor-2-dependent manner.2014

    • Author(s)
      Kai S, Tanaka T, Matsuyama T, Suzuki K, Hirota K.
    • Journal Title

      Eur J Pharmacol

      Volume: 732C Pages: 43-49

    • DOI

      10.1016/j.ejphar.2014.03.020

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 疾患の病態生理学と低酸素誘導性因子2013

    • Author(s)
      広田喜一
    • Journal Title

      細胞

      Volume: 45 Pages: 415-8

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 硫化水素はミトコンドリア依存的に低酸素誘導性遺伝子応答を調節する2013

    • Author(s)
      広田喜一
    • Journal Title

      Medical Gases

      Volume: 15 Pages: 25-7

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of decreased hypoxia-inducible factor 1 activity and resultant G(1)-S cell cycle transition in radioresistance of perinecrotic tumor cells2013

    • Author(s)
      Zhu Y, Zhao T, Itasaka S, Zeng L, Yeom CJ, Hirota K, Suzuki K, Morinibu A, Shinomiya K, Ou G, Yoshimura M, Hiraoka M, Harada H
    • Journal Title

      Oncogene

      Volume: 32 Pages: 2058-68

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] General Anesthetics Inhibit LPS-Induced IL-1beta Expression in Glial Cells.2013

    • Author(s)
      Tanaka T, Kai S, Matsuyama T, Adachi T, Fukuda K, Hirota K.
    • Journal Title

      Plos one

      Volume: 8 Pages: 82930-82930

    • DOI

      10.1371/journal.pone.0082930

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential roles of prostaglandin E-type receptors in activation of hypoxia-inducible factor 1 by prostaglandin E1 in vascular-derived cells under non-hypoxic conditions.2013

    • Author(s)
      Suzuki K, Nishi K, Takabuchi S, Kai S, Matsuyama T, Kurosawa S, Adachi T, Maruyama T, Fukuda K, Hirota K.
    • Journal Title

      Peer J

      Volume: 1 Pages: 1-20

    • DOI

      10.7717/peerj.220

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of gankyrin in mouse hepatocytes induces hemangioma by suppressing factor inhibiting hypoxia-inducible factor-1 (FIH-1) and activating hypoxia-inducible factor-12013

    • Author(s)
      Liu Y, Higashitsuji H, Higashitsuji H, Itoh K, Sakurai T, Koike K, Hirota K, Fukumoto M, Fujita J
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 132 Pages: 22-7

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of decreased hypoxia-inducible factor 1 activity and resultant G(1)-S cell cycle transition in radioresistance of perinecrotic tumor cells2013

    • Author(s)
      Y. Zhu, T. Zhao, S. Itasaka, L. Zeng, C.J. Yeom, K. Hirota, K. Suzuki, A. Morinibu, K. Shinomiya, G. Ou, M. Yoshimura, M. Hiraoka, H. Harada
    • Journal Title

      Oncogene

      Volume: 32 Pages: 2058-2068

    • DOI

      10.1038/onc.2012.223

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Overexpression of gankyrin in mouse hepatocytes induces hemangioma by suppressing factor inhibiting hypoxia-inducible factor-1 (FIH-1) and activating hypoxia-inducible factor-12013

    • Author(s)
      Y. Liu, H. Higashitsuji, K. Itoh, T. Sakurai, K. Koike, K. Hirota, M. Fukumoto, J. Fujita
    • Journal Title

      BBRC

      Volume: 432 Pages: 0-0

    • DOI

      10.1016/j.bbrc.2013.01.093

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] グルタミノリシス2012

    • Author(s)
      広田喜一
    • Journal Title

      がんと代謝(実験医学増刊)(東京 : 羊土社)(朋義曽,浩安江, editors)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of n-propyl gallate on neuronal survival after forebrain ischemia in rats2012

    • Author(s)
      Kawano Y, Kawaguchi M, Hirota K, Kai S, Konishi N, Furuya H
    • Journal Title

      Resuscitation

      Volume: 83 Pages: 249-52

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hydrogen sulfide inhibits hypoxia- but not anoxia-induced hypoxia-inducible factor 1 activation in a von hippel-lindau- and mitochondria-dependent manner2012

    • Author(s)
      Kai S, Tanaka T, Daijo H, Harada H, Kishimoto S, Suzuki K, Takabuchi S, Takenaga K, Fukuda K, Hirota K
    • Journal Title

      Antioxidants & redox signaling

      Volume: 16 Pages: 203-16

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hypoxia and hypoxia-inducible factor in inflammation2012

    • Author(s)
      Hirota K
    • Journal Title

      In : Roy S, editor. Chronic Inflammation : Molecular Pathophysiology, Nutritional and Therapeutic Interventions : Taylor & Francis

      Pages: 51-65

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cancer cells that survive radiation therapy acquire HIF-1 activity and translocate towards tumour blood vessels2012

    • Author(s)
      Harada H, Inoue M, Itasaka S, Hirota K, Morinibu A, Shinomiya K, Zeng L, Ou G, Zhu Y, Yoshimura M, McKenna WG, Muschel RJ, Hiraoka M
    • Journal Title

      Nature communications

      Volume: 3 Pages: 783-783

    • NAID

      120004007582

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cancer cells that survive radiation therapy acquire HIF-1 activity and translocate towards tumour blood vessels2012

    • Author(s)
      H. Harada, M. Inoue, S. Itasaka, K. Hirota,A. Morinibu, K. Shinomiya, L. Zeng, G. Ou, Y. Zhu, M. Yoshimura, W.G. McKenna, R.J. Muschel, M. Hiraoka
    • Journal Title

      Nat Commun

      Volume: 3 Pages: 783-783

    • DOI

      10.1038/ncomms1786

    • NAID

      120004007582

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hydrogen sulfide inhibits hypoxia- but not anoxia-induced hypoxia-inducible factor 1 activation in a von hippel-lindau- and mitochondria-dependent manner.2012

    • Author(s)
      甲斐慎一、田中具治、大条紘樹、原田浩、岸本俊、鈴木堅悟、高淵聡史、竹永敬三、福田和彦、広田喜一
    • Journal Title

      Antioxidants & Redox signaling

      Volume: 16 Pages: 203-216

    • DOI

      10.1089/ars.2011.3882

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of n-propyl gallate on neuronal survival after forebrain ischemia in rats2012

    • Author(s)
      Y. Kawano, M. Kawaguchi, K. Hirota, S. Kai, N. Konishi, H. Furuya
    • Journal Title

      Resuscitation

      Volume: 83 Pages: 249-252

    • DOI

      10.1016/j.resuscitation.2011.07.024

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hypoxia and hypoxia-inducible factor in inflammation2012

    • Author(s)
      Kiichi, Hirota
    • Journal Title

      Chronic Inflammation: Molecular Pathophysiology, Nutritional and Therapeutic Interventions

      Volume: 1 Pages: 51-65

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] グルタミノリシス2012

    • Author(s)
      広田喜一
    • Journal Title

      実験医学

      Volume: 30 Pages: 2400-2406

    • Related Report
      2012 Research-status Report
  • [Presentation] 麻酔薬は敗血症時の視床下部における炎症性サイトカイン誘導を抑制する2013

    • Author(s)
      田中具治,広田喜一,甲斐慎一,松山智紀,福田和彦
    • Organizer
      日本麻酔科学会第60回学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      2013-05-24
    • Related Report
      2013 Final Research Report
  • [Presentation] 神経因性疼痛モデルラット脊髄における低酸素誘導性因子とその下流遺伝子の発現について2013

    • Author(s)
      松山智紀, 佐々木美佳, 天谷文昌, 広田喜一, 福田和彦
    • Organizer
      日本麻酔科学会第60回学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      2013-05-24
    • Related Report
      2013 Final Research Report
  • [Presentation] シンポジウム急性肺損傷・肺循環障害の分子病態低酸素と肺胞炎症2013

    • Author(s)
      広田喜一
    • Organizer
      日本呼吸器学会
    • Place of Presentation
      東京都東京国際フォーラム
    • Year and Date
      2013-04-21
    • Related Report
      2013 Final Research Report
  • [Presentation] シンポジウム : 1S12低酸素応答が制御する多彩な生命現象-生理機能の解明から疾患に迫る-『炎症・インフラマソームのレドックス制御とTXNIP/HIF-1システム』2012

    • Author(s)
      広田喜一
    • Organizer
      第85回日本生化学会
    • Place of Presentation
      福岡市
    • Year and Date
      2012-12-14
    • Related Report
      2013 Final Research Report
  • [Presentation] 「低酸素研究の10年」hypoxia-inducible factorの20年と5つの未解決問題2012

    • Author(s)
      広田喜一
    • Organizer
      第10回がんとハイポキシア研究会
    • Place of Presentation
      横浜市横浜開港会館
    • Year and Date
      2012-12-06
    • Related Report
      2013 Final Research Report
  • [Presentation] シンポジウム「生体ガスと臓器保護」-「硫化水素はミトコンドリア依存的に低酸素誘導性遺伝子応答を調節する」2012

    • Author(s)
      広田喜一
    • Organizer
      第16回日本医療ガス学会学術大会・総会
    • Place of Presentation
      東京都東京ステーションコンファレンス
    • Year and Date
      2012-11-17
    • Related Report
      2013 Final Research Report
  • [Presentation] 「ハイポキシア生物学ー酸素代謝からみる生命現象の方程式」2012

    • Author(s)
      広田喜一
    • Organizer
      第47回日本高気圧環境・潜水医学会学術集会
    • Place of Presentation
      札幌市北海道大学学術交流会館
    • Year and Date
      2012-11-06
    • Related Report
      2013 Final Research Report
  • [Presentation] Odidative stress and Diseases2012

    • Author(s)
      Kiichi Hirota
    • Organizer
      33rd Naito Conference Oxygen Biology Hypoxia
    • Place of Presentation
      Sapporo
    • Year and Date
      2012-06-28
    • Related Report
      2013 Final Research Report
  • [Presentation] グリア細胞におけるLPS刺激によるIL-1beta遺伝子の発現は、全身麻酔薬により抑制される2012

    • Author(s)
      田中具治, 広田喜一, 甲斐慎一, 松山智紀, 福田和彦
    • Organizer
      日本麻酔科学会第59回学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-06-08
    • Related Report
      2013 Final Research Report
  • [Presentation] マイクログリアの活性化と酸素環境が低酸素誘導性遺伝子発現と神経因性疼痛関連遺伝子発現に与える影響2012

    • Author(s)
      松山智紀,廣田喜一, 鈴木堅悟, 甲斐慎一, 大条紘樹, 福田和彦
    • Organizer
      日本麻酔科学会第59回学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-06-07
    • Related Report
      2013 Final Research Report
  • [Presentation] イソフルランは、急性貧血により誘導される血中エリスロポエチンの上昇を抑制する2012

    • Author(s)
      甲斐慎一, 田中具治, 松山智紀, 大条紘樹, 広田喜一 ,福田和彦
    • Organizer
      日本麻酔科学会第59回学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-06-07
    • Related Report
      2013 Final Research Report
  • [Presentation] 炎症・インフラマソームのレドックス制御とTXNIP/HIF-1システム2012

    • Author(s)
      広田喜一
    • Organizer
      第85回日本生化学会 シンポジウム:1S12 低酸素応答が制御する多彩な生命現象 -生理機能の解明から疾患に迫る
    • Place of Presentation
      福岡市
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] TXNIP regulates the NLPR3 inflammatosome activity in a HIF-1- and thioredoxin-dependent manner in THP-1 macrophages2012

    • Author(s)
      Kiichi Hirota
    • Organizer
      33rd Naito Conference Oxygen Biology Hypoxia, Odidative stress and Diseases
    • Place of Presentation
      札幌市
    • Related Report
      2012 Research-status Report
  • [Presentation] hypoxia-indicible factorの20年と5つの未解決問題2012

    • Author(s)
      広田喜一
    • Organizer
      第10回がんとハイポキシア研究会
    • Place of Presentation
      横浜市
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] ハイポキシア生物学ー酸素代謝からみる生命現象の方程式2012

    • Author(s)
      広田喜一
    • Organizer
      第47回日本高気圧環境・潜水医学会学術集会
    • Place of Presentation
      札幌市
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 硫化水素はミトコンドリア依存的に低酸素誘導性遺伝子応答を調節する

    • Author(s)
      広田喜一
    • Organizer
      第16回日本医療ガス学会学術集会
    • Place of Presentation
      東京都
    • Related Report
      2012 Research-status Report
    • Invited

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Published: 2013-05-31   Modified: 2019-07-29  

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