Development the culture method for primary hepatocyte to keeping a same response range in vitro and in vivo for exogenous stimulus.
| Project/Area Number |
17K19916
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Health science and related fields
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| Research Institution | Saga University |
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Principal Investigator |
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | Nrf1 / 低酸素 / 肝細胞 / 初代培養 / 安全性試験 / 酸素 |
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| Outline of Final Research Achievements |
When we develop a primary hepatocyte in low oxygen condition from the beginning, the cellular motility of final hepatocyte is lower than when we conduct those strategy in normoxic condition. This method provided us to higher sensitivity for exogenous stimulus including oxidative stress and ER stress. In addition, the hepatocyte that was prepared in normoxic condition has lower levels of stress transcriptional factor, Nrf1 and Nrf2. This condition leads the hepatocyte to lower response fate for exogenous stimulus and lower detoxification activity. We have found that the glycomodifier enzyme, PNGase was contributed to controlling Nrf1 protein level during primary hepatocyte preparation in lower oxygen condition.
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| Academic Significance and Societal Importance of the Research Achievements |
10%程度の低酸素下での肝細胞を調整すると、酸化ストレス、小胞体ストレスなどの刺激に対する感受性が鋭敏になることが確認できた。今後、iPSから樹立されたヒト肝細胞を用いて、低酸素下で薬効試験等を行うことで、in vivoとin vitroとの感受性の乖離を減少させることが可能となり、早期に化合物の生体内での代謝評価を実施できると期待される。
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Furan- and Thiophene-2-Carbonyl Amino Acid Derivatives Activate Hypoxia-Inducible Factor via Inhibition of Factor Inhibiting Hypoxia-Inducible Factor-12018
Author(s)
Kawaguchi Shin-Ichi, Gonda Yuhei, Yamamoto Takuya, Sato Yuki, Shinohara Hiroyuki, Kobiki Yohsuke, Ichimura Atsuhiko, Dan Takashi, Sonoda Motohiro, Miyata Toshio, Ogawa Akiya, Tsujita Tadayuki
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Journal Title
Molecules
Volume: 23
Issue: 4
Pages: 885-885
DOI
Related Report
Peer Reviewed / Open Access
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