Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, Sappro 060-088, Japan.
J Biochem Mol Toxicol. 2012 Jan;26(1):16-22. doi: 10.1002/jbt.20408.
Sudan dyes possess a high affinity to the aryl hydrocarbon receptor (AHR) and potently induce its target genes, such as cytochrome P450 (CYP) 1A1, through unknown mechanisms. We investigated a detailed event occurring in cells after binding of Sudan dye to AHR in HepG2 cells. Treatment with 10 µM Sudan III caused rapid translocation of AHR into the nucleus and increased expression levels of human CYP1A1 mRNA by approximately 20-fold after 16 and 24 h. The transactivation was due to the activation of a region located at -1137 to +59 bp from CYP1A1, in particular, four xenobiotic responsive elements (XREs) existing in the region. AHR and the Ah receptor nuclear translocator interacted with XRE sequences in a gel shift assay using nuclear extract from Sudan III--treated HepG2 cells. Moreover, we suggest that constitutive androstane receptor could modify CYP1A1 transactivation by Sudan III.
苏丹染料对芳基烃受体 (AHR) 具有很高的亲和力，并通过未知机制强烈诱导其靶基因，如细胞色素 P450 (CYP) 1A1。我们研究了苏丹染料与 HepG2 细胞中的 AHR 结合后细胞中发生的详细事件。用 10 µM 苏丹 III 处理会导致 AHR 迅速转位到细胞核中，并在 16 和 24 小时后使人类 CYP1A1 mRNA 的表达水平增加约 20 倍。这种反式激活是由于 CYP1A1 从-1137 到+59 bp 处的一个区域的激活所致，特别是该区域存在四个外源响应元件 (XRE)。在使用苏丹 III 处理的 HepG2 细胞核提取物的凝胶迁移分析中，AHR 和 Ah 受体核转位蛋白与 XRE 序列相互作用。此外，我们认为，苏丹 III 可以通过组成型雄烷受体修饰 CYP1A1 的反式激活。
