Effects of Environmental Chemicals on Bone Metabolism through Steroid and Xenobiotic Receptor (SXR)
| Project/Area Number |
22591020
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | 公益財団法人冲中記念成人病研究所 (2012)
Okinaka Memorial Institute for Medical Research (2010-2011) |
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Principal Investigator |
TAKESHITA Akira 公益財団法人冲中記念成人病研究所, 研究員 (20322646)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Yasuhiro 冲中記念成人病研究所, 主任研究員 (50202164)
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| Co-Investigator(Renkei-kenkyūsha) |
KOIBUCHI Noriyuki 群馬大学, 医学研究科, 教授 (80234681)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 内分泌学 / SXR / 薬剤性骨軟化症 / 環境化学物質 / CYP3A4 / アセチルトリブチルクエン酸 / ビスフェノールA / フタル酸化合物 / TRPV6 |
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| Research Abstract |
Steroid and xenobiotic receptor (SXR) is activated by endogenous and exogenous chemicals. SXR is highly expressed in the liver and intestine, where it regulates CYP3A4, which in turn controls xenobiotic and endogenous hormone metabolism including active vitamin D. However, it is unclear whether drug additives exert such activity. We found that four of eight drug additives increased SXR-mediated transcription. In particular, acetyl tributyl citrate (ATBC), an industrial plasticizer widely used in products such as food wrap, vinyl toys, and pharmaceutical excipients, strongly activated SXR. Our in vitro and in vivo results suggest that ATBC specifically induces CYP3A in the intestine by activating SXR. We suggest that ATBC-containing products be used cautiously because they may alter metabolism of vitamin D.
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Report
(4 results)
Research Products
(14 results)
