Kim Eun-Young, Iwata Hisato, Suda Tomoko, Tanabe Shinsuke, Amano Masao, Miyazaki Nobuyuki, Petrov Evgeny A
Ehime Prefectural Institute of Public Health and Environmental Science, 8-234 Sanban-cho, Matsuyama 790-0003, Japan.
Comp Biochem Physiol C Toxicol Pharmacol. 2005 Jul;141(3):281-91. doi: 10.1016/j.cca.2005.07.007.
Most toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related planar halogenated aromatic hydrocarbons (PHAHs) are mediated by ligand-activated aryl hydrocarbon receptor (AHR) signaling pathway. To understand the regulation mechanism of AHR and AHR nuclear translocator (ARNT) expression in wild Baikal seal (Pusa sibirica) population contaminated by PHAHs, the present study investigated hepatic mRNA expression levels of AHR and its heterodimer, ARNT genes, in association with biological index (age, gender and body weight), PHAH accumulation and expression levels of cytochrome P450 (CYP) 1A and 1B. While there was no gender difference, the AHR mRNA expression levels were increased with ages (p = 0.014) and body weights (p = 0.015), indicating that AHR expression might be affected by these biological factors. The AHR mRNA expression levels exhibited significant positive correlations with total TEQs and most of individual congener TEQs derived from polychorinated dibenzo-p-dioxins, dibenzofurans and non-ortho coplanar polychorinated biphenyls (PCBs), indicating the transcriptional up-regulation of AHR expression by these congeners. On the other hand, there was no significant correlation between individual TEQs from mono-ortho coplanar PCBs and AHR expression. These results imply the structure-related transcriptional activity of AHR among PHAHs congeners. AHR mRNA levels showed positive correlations with both CYP1A protein (p = 0.039) and CYP1A1 mRNA expression levels (p = 0.046). In contrast to AHR expression, neither the total nor individual congener TEQs influenced ARNT at the transcriptional level. ARNT mRNA showed significant negative correlations with CYP1A/1B protein (p = 0.027 and p = 0.006) and CYP1A1 mRNA expression levels (p = 0.039), implying the existence of different transcriptional regulation between AHR and ARNT genes and negative regulation by CYP1A/1B-mediated signaling pathways. The present findings may render significant insight on the basic mechanisms underlying regulation of AHR and ARNT expressions associated with biological factors and PHAH exposure in wild mammalian populations.
2,3,7,8-四氯二苯并-对-二噁英（TCDD）及相关平面卤代芳烃（PHAHs）的大多数毒性作用是由配体激活的芳烃受体（AHR）信号通路介导的。为了解在受PHAHs污染的野生贝加尔海豹（Pusa sibirica）种群中AHR和AHR核转运蛋白（ARNT）表达的调控机制，本研究调查了AHR及其异二聚体ARNT基因的肝脏mRNA表达水平，以及与生物学指标（年龄、性别和体重）、PHAH蓄积量和细胞色素P450（CYP）1A和1B表达水平的关系。虽然不存在性别差异，但AHR mRNA表达水平随年龄（p = 0.014）和体重（p = 0.015）增加，表明AHR表达可能受这些生物学因素影响。AHR mRNA表达水平与多氯二苯并-对-二噁英、二苯并呋喃和非邻位共平面多氯联苯（PCBs）衍生的总毒性当量（TEQs）以及大多数单个同系物TEQs呈显著正相关，表明这些同系物可使AHR表达发生转录上调。另一方面，单邻位共平面PCBs的单个TEQs与AHR表达之间无显著相关性。这些结果提示了PHAHs同系物中AHR与结构相关的转录活性。AHR mRNA水平与CYP1A蛋白（p = 0.039）和CYP1A1 mRNA表达水平（p = 0.046）均呈正相关。与AHR表达不同，总TEQs和单个同系物TEQs在转录水平上均未影响ARNT。ARNT mRNA与CYP1A/1B蛋白（p = 0.027和p = 0.006）以及CYP1A1 mRNA表达水平（p = 0.039）呈显著负相关，这意味着AHR和ARNT基因存在不同的转录调控，且CYP1A/1B介导的信号通路存在负调控。本研究结果可能为深入了解野生哺乳动物种群中与生物学因素和PHAH暴露相关的AHR和ARNT表达调控的基本机制提供重要见解。
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