Cytotoxicity caused by long-term propofol treatment in human induced pluripotent stem cell-derived cell lines
| Project/Area Number |
16K20380
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Emergency medicine
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
ITO Hiroyuki 東京医科歯科大学, 医学部附属病院, 助教 (80595554)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| 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)
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| 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 |
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| 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.
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Report
(3 results)
Research Products
(3 results)
