Clarification of factors governing sensitivity of disruption of intracellular receptor-xenobiotic metabolizing enzyme signaling pathways by chemical substances

阐明化学物质对细胞内受体-外源代谢酶信号通路破坏敏感性的影响因素

• 批准号: 21221004
• 负责人: IWATA HISATO
• 金额: $ 140.52万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009-05-11 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21221004/
• 关键词: 化学物質; 細胞内受容体; シトクロムP450; 感受性; 野生動物; 異物代謝酵素; 細胞内受容; リスク評価; シトクロムP450 (cytochrome P450); aryl hydrocarbon receptor (AHR); constitutive androstane receptor (CAR); pregnane X receptor (PXR); peroxisome proliferator-activated receptor (PPAR); pers

The achievements of this study are summarized as follows;1) for the screening of toxic environmental pollutants, we succeeded in developing in vitro assay systems that intracellular receptor proteins of wild animals are expressed, 2) the intracellular receptor proteins showed species- and isoform-specific responses to the exposure to toxic environmental pollutants, 3) the in vitro assay systems enabled us to assess the risk incorporating the interspecies differences in susceptibility in some wild populations, 4) certain amino acid residues that were evolutionary mutated contribute to the ligand interaction of intracellular receptors and cytochrome P450, and 5) there are factors responsible for the susceptibility other than intracellular receptors and cytochrome P450.

本研究的成果概括如下：1）针对有毒环境污染物的筛选，我们成功开发了野生动物细胞内受体蛋白表达的体外检测系统，2）细胞内受体蛋白对有毒环境污染物的暴露表现出物种和异构体特异性的反应，3）体外检测系统使我们能够评估跨物种的风险 一些野生群体中易感性的差异，4）进化突变的某些氨基酸残基有助于细胞内受体和细胞色素P450的配体相互作用，5）除了细胞内受体和细胞色素P450之外，还有其他因素导致易感性。

项目成果

Characterization of a Novel Type I Keratin Gene and Generation of Transgenic Lines With Fluorescent Reporter Genes Driven by Its Promoter/Enhancer in Xenopus laevis

• DOI: 10.1002/dvdy.22451
• 发表时间: 2010-12-01
• 期刊: DEVELOPMENTAL DYNAMICS
• 影响因子: 2.5
• 作者: Suzuki, Ken-Ichi T.;Kashiwagi, Keiko;Mochii, Makoto
• 通讯作者: Mochii, Makoto

Genetic polymorphisms in glutathione S-transferase (GST) superfamily and arsenic metabolism in residents of the Red River Delta, Vietnam

• DOI: 10.1016/j.taap.2009.11.007
• 发表时间: 2010-02-01
• 期刊: TOXICOLOGY AND APPLIED PHARMACOLOGY
• 影响因子: 3.8
• 作者: Agusa, Tetsuro;Iwata, Hisato;Tanabe, Shinsuke
• 通讯作者: Tanabe, Shinsuke

Genetic polymorphisms in AS3MT and arsenic metabolism in residents of the Red River Delta, Vietnam

• DOI: 10.1016/j.taap.2009.01.015
• 发表时间: 2009-04-15
• 期刊: TOXICOLOGY AND APPLIED PHARMACOLOGY
• 影响因子: 3.8
• 作者: Agusa, Tetsuro;Iwata, Hisato;Tanabe, Shinsuke
• 通讯作者: Tanabe, Shinsuke

Human exposure to arsenic from groundwater in the Red River and Mekong River Deltas in Vietnam

• DOI: 10.1080/00207230902759962
• 发表时间: 2009-01-01
• 期刊: International Journal of Environmental Studies
• 作者: Agusa, Tetsuro;Inoue, Suguru;Tanabe, Shinsuke
• 通讯作者: Tanabe, Shinsuke

In vitro transactivation potencies of black-footed albatross (Phoebastria nigripes) AHR1 and AHR2 by dioxins to predict CYP1A expression in the wild population

二恶英对黑足信天翁 (Phoebastria nigripes) A​​HR1 和 AHR2 的体外反式激活效力可预测野生种群中 CYP1A 的表达

• DOI: 10.1021/es2028263
• 发表时间: 2012
• 期刊: Environmental Science and Technology
• 影响因子: 11.4
• 作者: Thuruthippallil;L. M.
• 通讯作者: L. M.