2002 Fiscal Year Final Research Report Summary
Development of New Screening Method for Endocrine Disruptors and Analyses of Disrupting Mechanisms
| Project/Area Number |
11557198
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Environmental pharmacy
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| Research Institution | Graduate School of Pharmaceutical Sciences, Nagoya City University (2000-2002)
Osaka University (1999) |
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Principal Investigator |
IMAGAWA Masayoshi Nagoya City Univ., Pharm. Sci., Prof., 大学院・薬学研究科, 教授 (20136823)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIKAWA Jun-ichi Osaka Univ., Pharm. Sci., Assoc. Prof., 大学院・薬学研究科, 助教授 (90218131)
TSUKAMOTO Kikuo Nagoya City Univ., Pharm. Sci., Assist. Prof., 大学院・薬学研究科, 講師 (20183478)
TAGUCHI Ryo Nagoya City Univ., Pharm. Sci., Assoc. Prof., 大学院・薬学研究科, 助教授 (20080210)
NISHIHARA Tsutomu Osaka Univ., Pharm. Sci., Prof., 大学院・薬学研究科, 教授 (50028859)
SAITO Koichi Sumitomo Chemical Co. Ltd., Senior Scientist, 主任研究員
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| Project Period (FY) |
1999 – 2002
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| Keywords | endocrine disruptors / estrogen receptor / cofactor / yeast / screening method / nuclear receptor |
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| Research Abstract |
The endocrine systems are involved in the multitude of physiological processes. Recently, the endocrine disrupting chemicals are thought to have some effects in these processes. Therefore, it is important to develop a screening method for chemicals having these activities, and also characterize a disrupting mechanism.
1) We developed a new screening method for chemicals having hormonal activities using yeast two-hybrid system.
2) Using this assay system, we tested more than five hundred chemicals and discussed the structure-activity relationship.
3) We demonstrated that PPAR_γ (peroxisome proliferator-activated receptor γ), which is one of the nuclesr receptor, has dual DNA binding specificity. When PPARγ makes homodimer binds to estrogen receptor binding sequences rather than direct repeat.
4) We established PPARγ-expressing cells. Using this cell line, we isolated the new target genes of PPARγ using subtraction protocol and two-dimensional electrophoresis.
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[Publications] Nishikawa,J., Saito,K., Goto,J., Dakeyama,F., Matsuo,M., and Nishihara,T.: "New Screening methods for chemicals with hormonal activities using interaction of nuclear hormone receptor with coactivator"Toxicol. Appl. Pharmcol.. 154(1). 76-83 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Nishihara,T., Nishikawa,J., Kanayama,T., Dakeyama,F., Saito,K., Imagawa,M., Takatori,S., Kitagawa,Y., Hori,S., Utsumi,H.: "Estrogenic activities of 517 chemicals by yeast two-hybrid assay"J. Health Sci.. 46(4). 282-298 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Okuno,M., Arimoto,E., Ikenobu,Y., Nishihara,T., and Imagawa,M.: "Dual DNA binding specificity of peroxisome proliferator-activated receptorγ controlled heterodimer formation with retinoid X receptorα"Biochem., J.. 353(2). 193-198 (2001)
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「研究成果報告書概要(欧文)」より
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