State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center of Eco-Environment Sciences, Chinese Academy of Sciences, 18 Shuangqing Rd, Haidian District, Beijing, 100085, China; Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Shandong Academy of Sciences, Jinan, Shandong, 250014, China; University of Chinese Academy of Sciences, 19 A Yuquan Rd, Shijingshan District, Beijing, 100049, China.
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center of Eco-Environment Sciences, Chinese Academy of Sciences, 18 Shuangqing Rd, Haidian District, Beijing, 100085, China; University of Chinese Academy of Sciences, 19 A Yuquan Rd, Shijingshan District, Beijing, 100049, China.
Environ Pollut. 2018 Jun;237:508-514. doi: 10.1016/j.envpol.2018.02.079. Epub 2018 Mar 15.
The aryl hydrocarbon receptor (AhR) plays an important role in mediating dioxins toxicity. Currently, genes of P450 families are major research interests in studies on AhR-mediated gene alterations caused by dioxins. Genes related to other metabolic pathways or processes may be also responsive to dioxin exposures. Amino acid transporter B0AT1 (encoded by SLC6A19) plays a decisive role in neutral amino acid transport which is present in kidney, intestine and liver. However, effects of dioxins on its expression are still unknown. In the present study, we focused on the effects of dioxin and dioxin-like compounds on SLC6A19 expression in HepG2 cells. We identified SLC6A19 as a novel putative target gene of AhR activation in HepG2 cells. 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) increased the expression of SLC6A19 in time- and concentration-dependent manners. Using AhR antagonist CH223191 and/or siRNA assays, we demonstrated that certain AhR agonists upregulated SLC6A19 expression via AhR, including TCDD, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (1,2,3,7,8-PeCDD), 2,3,4,7,8- pentachlorodibenzofuran (2,3,4,7,8-PeCDF) and PCB126. In addition, the expression of B0AT1 was also significantly induced by TCDD in HepG2 cells. Our study suggested that dioxins might affect the transcription and translation of SLC6A19 in HepG2 cells, which might be a novel putative gene to assess dioxins' toxicity in amino acid transport and metabolism in liver.
芳香烃受体 (AhR) 在介导二恶英毒性方面发挥着重要作用。目前，P450 家族的基因是研究二恶英引起的 AhR 介导的基因改变的主要研究对象。其他代谢途径或过程相关的基因也可能对二恶英暴露有反应。氨基酸转运体 B0AT1（由 SLC6A19 编码）在肾脏、肠道和肝脏中发挥着决定性作用，负责中性氨基酸的转运。然而，二恶英对其表达的影响尚不清楚。在本研究中，我们专注于二恶英和类二恶英化合物对 HepG2 细胞中 SLC6A19 表达的影响。我们确定 SLC6A19 是 HepG2 细胞中 AhR 激活的一个新的潜在靶基因。2,3,7,8-四氯二苯并对二恶英（TCDD）以时间和浓度依赖的方式增加 SLC6A19 的表达。使用 AhR 拮抗剂 CH223191 和/或 siRNA 测定，我们证明某些 AhR 激动剂通过 AhR 上调 SLC6A19 的表达，包括 TCDD、1,2,3,7,8-五氯二苯并对二恶英（1,2,3,7,8-PeCDD）、2,3,4,7,8-五氯二苯并呋喃（2,3,4,7,8-PeCDF）和 PCB126。此外，TCDD 还显著诱导 HepG2 细胞中 B0AT1 的表达。我们的研究表明，二恶英可能会影响 HepG2 细胞中 SLC6A19 的转录和翻译，这可能是评估二恶英在肝脏氨基酸转运和代谢中毒性的一个新的潜在基因。
