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Cytotoxicity caused by long-term propofol treatment in human induced pluripotent stem cell-derived cell lines

Research Project

Project/Area Number 16K20380
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Emergency medicine
Research InstitutionTokyo Medical and Dental University

Principal Investigator

ITO Hiroyuki  東京医科歯科大学, 医学部附属病院, 助教 (80595554)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsプロポフォール / 毒性 / ヒト人工多能性幹細胞 / 神経細胞 / アポトーシス
Outline of Final Research Achievements

Cultured human induced pluripotent stem (iPS) cell-derived neurons was used to study the toxic effects of propofol on human neurons. Human iPS cell-derived neural stem cells were cultured for 14 days and differentiated into neurons. These neurons were exposed to propofol for 48 hours. Propofol at 10μg/ml reduced NAD/NADH ratio by 24.6 %, cell viability by 12.3%, and caspase 3/7 activity was increased by 20.3%. Higher concentration of propofol (50μg/ml) caused further reduction in ATP level (17.9%), NAD/NADH ratio (40.1 %) and cell viability (15.9%), whereas augmentation in caspase 3/7 activity by 24.0%. Transmission electron microscopy showed autophagosomes, fragmentated mitochondria, and many vacuoles in the cytoplasm at 50μg/ml. Propofol dose-dependently reduced cell viability in cultured neuron at the range above clinical plasma concentration. Inhibitory effect on electron transport might reduce ATP production, which might result in the mitochondrial dysfunction.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2018 2016

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

  • [Journal Article] Cytotoxicity of propofol in human induced pluripotent stem cell-derived cardiomyocytes.2018

    • Author(s)
      Kido K, Ito H, Yamamoto Y, Makita K, Uchida T
    • Journal Title

      J Anesth

      Volume: 32 Issue: 1 Pages: 120-131

    • DOI

      10.1007/s00540-017-2441-0

    • NAID

      40021468186

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Dose-dependent Cytotoxicity of Propofol in Cultured Human-induced Pluripotent Stem Cell-derived Neurons2016

    • Author(s)
      Koji Kido, Hiroyuki Ito, Yudai Yamamoto, Tokujiro Uchida, Koshi Makita
    • Organizer
      Anesthesiology 2016
    • Place of Presentation
      Chicago, Illinois、USA
    • Year and Date
      2016-10-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒト人工多能性幹細胞由来神経細胞を用いたプロポフォール長時間曝露による毒性評価:ミトコンドリア機能障害およびアポトーシス誘導に関する検討2016

    • Author(s)
      木戸浩司, 内田篤治郎, 山本雄大, 伊藤裕之、 槇田浩史
    • Organizer
      日本麻酔科学会第63回学術集会
    • Place of Presentation
      福岡国際会議場、福岡県福岡市
    • Year and Date
      2016-05-26
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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