Bank P A, Yao E F, Phelps C L, Harper P A, Denison M S
Department of Biochemistry, Michigan State University, East Lansing 48824.
Eur J Pharmacol. 1992 Sep 1;228(2-3):85-94. doi: 10.1016/0926-6917(92)90016-6.
The Ah receptor (AhR) mediates many, if not all, of the toxic and biological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related halogenated aromatic hydrocarbons. Although wide variations in species sensitivity to these compounds have been observed, numerous biochemical and physiochemical characteristics of the AhR appear similar among species. We have examined the ability of cytosolic AhR, from a variety of species (rat, rabbit, guinea pig, hamster, mouse, cow, sheep, fish, chicken and human), to transform and bind to its cognate DNA recognition sequence, the dioxin responsive enhancer (DRE), to evaluate the importance of these events in species variations in TCDD responsiveness. Gel retardation analysis using a murine DRE oligonucleotide has revealed that cytosolic AhR from a wide variety of species can transform in vitro and bind to the DRE and demonstrates that all of the factors necessary for AhR transformation and DNA binding are present in cytosol. In addition, DNA-binding analysis using a series of mutant DRE oligonucleotides has indicated no apparent species- or ligand-dependent, nucleotide-specific difference in AhR binding to the DRE. These studies support a highly conserved nature of the DRE and AhR (at least in DNA binding) and imply that a sequence closely related to the murine consensus DRE sequence is responsible for conferring AhR-dependent, TCDD responsiveness in each of these species.
芳烃受体（AhR）介导了2,3,7,8-四氯二苯并对二恶英（TCDD，二恶英）及相关卤代芳烃的许多（即便不是全部）毒性和生物学效应。尽管已观察到不同物种对这些化合物的敏感性存在很大差异，但AhR的众多生化和理化特性在各物种间似乎相似。我们检测了来自多种物种（大鼠、兔子、豚鼠、仓鼠、小鼠、牛、羊、鱼、鸡和人类）的胞质AhR转化并结合其同源DNA识别序列——二恶英反应增强子（DRE）的能力，以评估这些事件在TCDD反应性物种差异中的重要性。使用小鼠DRE寡核苷酸进行的凝胶阻滞分析表明，来自多种物种的胞质AhR能够在体外转化并结合DRE，这表明AhR转化和DNA结合所需的所有因子都存在于胞质中。此外，使用一系列突变DRE寡核苷酸进行的DNA结合分析表明，AhR与DRE的结合不存在明显的物种或配体依赖性核苷酸特异性差异。这些研究支持了DRE和AhR具有高度保守性（至少在DNA结合方面），并暗示与小鼠共有DRE序列密切相关的序列负责赋予这些物种中每一个物种AhR依赖性的TCDD反应性。
