Sensitivity of avian species to the aryl hydrocarbon receptor ligand 6-formylindolo [3,2-b] carbazole (FICZ)
Sensitivity of avian species to the aryl hydrocarbon receptor ligand 6-formylindolo [3,2-b] carbazole (FICZ)
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DOI：
10.1016/j.cbi.2014.07.009
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发表时间：
2014-09-25
影响因子：
5.1
通讯作者：
Kennedy, Sean W.
中科院分区：
文献类型：
--
作者：
Farmahin, Reza;Crump, Doug;Kennedy, Sean W.
鸟类物种对二恶英样化合物（dlc）毒性作用的敏感性不同，最近的报告对这种差异背后的分子机制提供了深入了解。鸟类对dlc的敏感性与芳烃受体I （AHRI）的配体结合域（LBD） 324和380位氨基酸的特性有关。6-甲酰基林多洛[3,2-b]咔唑（FICZ）是一种天然产生的色氨酸光氧化产物，是一种高效的AHR配体。很少有研究试图以系统的方式确定FICZ对AHR的激活是否存在物种差异。在这里，我们描述了一项体外实验的结果，该实验测量了AHRI介导的荧光素酶报告基因活性，以确定FICZ和2,3,7,8-四氯二苯二恶英（TCDD）在COS-7细胞中的浓度依赖性效应，这些细胞转染了来自鸡（Gallus Gallus）、环颈雉（Phasianus colchicus）、日本鹌鹑（Coturrzix japonica）和常青鸟（Sterna hi rondo）的AHR1构建物，以及三种突变AHR1构建物。数据用于(a)比较FICZ和TCDD对每个AHR1构建体的效力（相对效力；Rep）和(b)每个构建体对FICZ和TCDD激活AHR1的敏感性（相对敏感性；ReS）。结果表明：(1)FICZ在鸡AHR1 （RePavg = 41）、环颈雉AHRI （RePavg = 93）、日本鹌鹑AHRI （RePavg = 1392）和常鸟AHRI （RePavg = 1534）转染细胞中的作用明显强于TCDD；(2)表达鸡、野鸡、鹌鹑和常鸟AHRI的细胞对FICZ的敏感性差异不显著，但对TCDD的敏感性差异显著；(3)在FICZ作用下，324位和380位氨基酸的改变对禽AHR1活性没有影响；(4)COS-7细胞中FICZ的相对效力没有时间依赖性变化；(5)FICZ和TCDD均未诱导COS-7细胞中乙氧基间苯二酚o -去乙基酶（EROD）活性。结果表明，FICZ和TCDD通过不同的相互作用方式激活AHR1。爱思唯尔爱尔兰有限公司版权所有版权所有。
Avian species differ in sensitivity to the toxic effects of dioxin-like compounds (DLCs) and recent reports have provided insight into the molecular mechanisms underlying this variability. The sensitivity of avian species to DLCs is associated with the identity of amino acids at positions 324 and 380 within the ligandbinding domain (LBD) of the aryl hydrocarbon receptor I (AHRI). 6-formylindolo [3,2-b] carbazole (FICZ), a naturally produced photo-oxidation product of tryptophan, is a highly potent AHR ligand. Few studies have attempted to determine if there are species differences in AHR activation by FICZ in a systematic manner. Here we describe results from an in vitro assay that measures AHRI -mediated luciferase reporter gene activity to determine concentration-dependent effects of FICZ and 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) in COS-7 cells transfected with AHR1 constructs from chicken (Gallus gallus domesticus), ring-necked pheasant (Phasianus colchicus), Japanese quail (Coturrzix japonica) and common tern (Sterna hi rondo), and three mutant AHR1 constructs. Data were used to (a) compare the potency of FICZ and TCDD for each AHR1 construct (relative potency; Rep) and (b) the sensitivity of each construct to AHR1 activation by FICZ and TCDD (relative sensitivity; ReS). The results show that (1) FICZ was considerably more potent than TCDD in cells transfected with chicken AHR1 (RePavg = 41), ring-necked pheasant AHRI (RePavg = 93), Japanese quail AHRI (RePavg = 1392) and common tern AHRI (RePavg = 1534), (2) there were no significant differences in sensitivity to FICZ in cells expressing chicken, pheasant, quail and tern AHRI, but there were significant differences in sensitivity to TCDD, (3) alteration of amino acids at positions 324 and 380 had no effect on avian AHR1 activity in response to FICZ, (4) there was no timedependent change in the relative potency of FICZ in COS-7 cells, and (5) neither FICZ nor TCDD induced ethoxyresorufin O-deethylase (EROD activity) in COS-7 cells. Our results suggest that FICZ and TCDD activate avian AHR1 by different modes of interaction with AHR1. Crown Copyright (C) 2014 Published by Elsevier Ireland Ltd. All rights reserved.