Pendurthi U R, Okino S T, Tukey R H
Department of Pharmacology, UCSD Cancer Center, San Diego, La Jolla 92093.
Arch Biochem Biophys. 1993 Oct;306(1):65-9. doi: 10.1006/abbi.1993.1481.
The treatment of C57BL/6 mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to the nuclear uptake of the arylhydrocarbon receptor (AhR) and transcriptional activation of Cyp1a-1 and Cyp1a-2 (S. T. Okino, et al., J. Biol. Chem. 267, 6991, 1992). In the present study, early nuclear uptake of the AhR and its role in transcriptional activation of the Cyp1 genes have been evaluated. After 30 min following a dose of TCDD to C57BL/6 mice, the AhR could be detected in liver nuclei. The effect of TCDD treatment within 30 min enhanced the transcriptional rate of the Cyp1a-2 gene to 70% of its maximal rate, with maximal levels of transcription occurring after 1 h. Early increases in 1a-2 mRNA were also observed by 30 min and increased to maximal levels by 12 h. In contrast, the levels of Cyp1a-1 transcription were 5 to 10% of maximal levels at 30 min, and gradually increased to maximal levels by 2 h. Concordant with the levels of transcription, 1a-1 mRNA was not detected until 1 h following TCDD treatment. While the AhR is responsible for transcriptional activation of the Cyp1a-1 gene, the concordant increase in the nuclear accumulation of the ligand-dependent AhR and Cyp1a-2 gene transcription suggests that the receptor plays an important role in the regulation of the Cyp1a-2 gene.
用2,3,7,8-四氯二苯并对二恶英（TCDD）处理C57BL/6小鼠会导致芳烃受体（AhR）的核摄取以及Cyp1a-1和Cyp1a-2的转录激活（S.T.奥基诺等人，《生物化学杂志》267卷，6991页，1992年）。在本研究中，对AhR的早期核摄取及其在Cyp1基因转录激活中的作用进行了评估。给C57BL/6小鼠注射一剂TCDD后30分钟，可在肝细胞核中检测到AhR。30分钟内TCDD处理的效果将Cyp1a-2基因的转录速率提高到其最大速率的70%，最大转录水平在1小时后出现。在30分钟时也观察到1a-2 mRNA的早期增加，并在12小时时增加到最大水平。相比之下，Cyp1a-1转录水平在30分钟时为最大水平的5%至10%，并在2小时时逐渐增加到最大水平。与转录水平一致，直到TCDD处理后1小时才检测到1a-1 mRNA。虽然AhR负责Cyp1a-1基因的转录激活，但配体依赖性AhR的核积累与Cyp1a-2基因转录的一致增加表明该受体在Cyp1a-2基因的调控中起重要作用。
