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Toxic mechanisms and metabolism of endogenous and exogenous AhR ligands

内源性和外源性AhR配体的毒性机制和代谢

基本信息

批准号：
16201012
负责人：
MATSUI Saburo
金额：
$ 31.7万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16201012/
关键词：
Arylhydrocarbon Receptor (AhR)Indirubin Indole compounds dye dioxin AhR LC MS 多環芳香族化合物

项目摘要

Arylhydrocarbon Receptor (AhR) recognizes wide variety of chemicals as its ligand. It is widely known that many persistent organic pollutants (POPs) such as polychlorinated dibenzo-dioxins (PCDDs), polychlorinated dibenzo-furans (PCDFs), polychlorinated biphenyls (PCBs) and polyaromatic hydrocarbons (PAHs) are AhR ligands. It is also known that some natural indole compounds, such as indole[3,2-b]carbazole (ICZ), 3,3'-diindolylmethane (DIM), 6-folmylindolo [3,2-b]carbazole (FICZ) show strong AhR ligand activity. Our group also has found one of the strongest AhR ligand, indirubin. In this study, we detected and identified the new AhR ligands in the environment and in food. We identified several AhR ligands in the effluent from dye works and a municipal waste water treatment plant. Those AhR lingads were dyes which are widely used. We showed AhR ligand activity in several commercially obtained anthraquinone dyes. We also found that there were several AhR ligands in coffee extract.We compared the activity of several natural AhR ligands, DIM,ICZ,FICZ and indirubin. ICZ,FICZ and indirubin all showed very strong activity. However, the activity was vanished when they were incubated with CYP1A1 or CYP1A2,which are the monooxigenases induced via AhR signaling. The difference of toxicity between these natural ligands and dioxins may be due to their metabolic propaties.

芳烃受体（Arylhydrocarbon Receptor，AhR）识别多种化学物质作为其配体。众所周知，许多持久性有机污染物（POPs）如多氯二苯并二恶英（PCDDs）、多氯二苯并呋喃（PCDFs）、多氯联苯（PCBs）和多环芳烃（PAHs）都是AhR配体。一些天然吲哚类化合物如吲哚[3，2-B]咔唑（ICZ）、3，3 '-二吲哚甲烷（DIM）、6-甲酰吲哚并[3，2-B]咔唑（FICZ）等也显示出较强的配体活性。本课题组还发现了最强的AhR配体靛玉红。在这项研究中，我们检测和鉴定了新的AhR配体在环境和食品中。我们确定了几个AhR配体的废水从染料厂和城市污水处理厂。这些AhR lingads是广泛使用的染料。我们在几种商业上获得的蒽醌染料中显示了AhR配体活性。我们还发现咖啡提取物中含有多种AhR配体，并比较了几种天然AhR配体DIM、ICZ、FICZ和靛玉红的活性。ICZ、FICZ和靛玉红均表现出很强的活性。然而，当它们与CYP 1A 1或CYP 1A 2孵育时，活性消失，CYP 1A 1或CYP 1A 2是通过AhR信号转导诱导的单加氧酶。这些天然配体与二恶英的毒性差异可能是由于它们的代谢特性。

项目成果

期刊论文数量（51）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

4-oxo-2-hexenal, a mutagen formed by omega-3 fat peroxidation, causes DNA adduct formation in mouse organs.

4-oxo-2-hexenal 是一种由 omega-3 脂肪过氧化形成的诱变剂，可导致小鼠器官中 DNA 加合物的形成。

DOI：
发表时间：
2005
期刊：
Ind.Health. 43
影响因子：
0
作者：
Kawai;K.;Svoboda;P.;Kasai;Arakawa R.;Negishi K.;Takahashi E.;Arimoto-Kobayashi S.;Svoboda P.;Kasai H.;Kawai K.;Maekawa M.;Eizo Takahashi;Hidetomo Kobayashi;Sakae Arimoto-Kobayashi;Kazuaki Kawai;Muneyuki Maekawa;Kentaro Taira;Koji Seio;Hiroshi Kasai
通讯作者：
Hiroshi Kasai

Arylhydrocarbon receptor ligand acitivity of indirubin

靛玉红的芳基烃受体配体活性

DOI：
发表时间：
2006
期刊：
Indirubin, the red shade of indigo (Life in Progress Editions, Roscoff, France)
影响因子：
0
作者：
T.Matsuda;J.Adachi
通讯作者：
J.Adachi

Translesion synthesis past 2'-deoxyxanthosine, a nitric oxide-derived DNA adduct, by mammalian DNA polymerases.

通过哺乳动物 DNA 聚合酶跨损伤合成 2-脱氧黄苷（一种一氧化氮衍生的 DNA 加合物）。

DOI：
10.1016/j.jmb.2004.09.064
发表时间：
2004
期刊：
Journal of molecular biology.
影响因子：
0
作者：
Yasui,Manabu;Suzuki,Naomi;Miller,Holly;Matsuda,Tomonari;Matsui,Saburo;Shibutani,Shinya
通讯作者：
Shibutani,Shinya

「AhRの内因性リガンド」-外因性リガンド多環芳香族と内因性リガンド-インディゴ・イン

“AhR 的内源性配体” - 外源性配体多环芳烃和内源性配体 - Indigo In