Assessment of toxicity associated with protein degradation of drug-metabolizing enzymes by cehemicals in three-dimensional culture
| Project/Area Number |
26293029
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Environmental and hygienic pharmacy
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| Research Institution | Hiroshima University |
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Principal Investigator |
Ohta Shigeru 広島大学, 大学院医歯薬保健学研究院(薬), 教授 (60160503)
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| Co-Investigator(Kenkyū-buntansha) |
佐能 正剛 広島大学, 医歯薬保健学研究院(薬), 助教 (00552267)
古武 弥一郎 広島大学, 医歯薬保健学研究院(薬), 准教授 (20335649)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Keywords | 薬物代謝酵素 / ユビキチンプロテアソーム / アセトアミノフェン / 3次元培養 / 化学物質 / オートファジー |
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| Outline of Final Research Achievements |
There are few reports regarding toxicity and enzyme activity associated with drug-metabolizing enzyme accumulated by disruption of its protein degradation system. We have clarified that acetaminophen led to inhibit CYP3A protein degradation and accordingly induced its enzyme activity using 3-dimensional hepatocyte culture. The results could contribute formation of the reactive metabolite by CYP3A, which is known to induce hepatotoxicity. Acetaminophen analog also showed inhibitory effects on CYP3A degradation in 3-dimensional culture. These findings could lead to clarify the detailed mechanism.
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Report
(4 results)
Research Products
(17 results)
