Internal genomic sequence of human CYP1A1 gene is involved in superinduction of dioxin-induced CYP1A1 transcription by cycloheximide
Internal genomic sequence of human CYP1A1 gene is involved in superinduction of dioxin-induced CYP1A1 transcription by cycloheximide
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DOI：
10.1016/j.bbrc.2007.02.010
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发表时间：
2007-04-13
影响因子：
3.1
通讯作者：
Ohsako, Seiichiroh
中科院分区：
文献类型：
--
作者：
Sakata, Yoshinori;Yoshioka, Wataru;Ohsako, Seiichiroh
2，3，7，8-四氯二苯并-对-二恶英（TCDD）诱导CYP 1A 1 mRNA表达，与蛋白质合成抑制剂放线菌酮（CHX）共处理进一步放大其表达数倍。虽然这种现象已被报道为超诱导，但其分子机制仍然不清楚。在本研究中，我们分析了CYP 1A 1内部基因组序列对CHX介导的超诱导的影响。将人CYP 1A 1的部分序列插入到与荧光素酶cDNA连接的内部核糖体进入位点（IRES）的5'末端，并将产生的构建体瞬时转染到CHO或HcpG 2细胞中。内含子-1缺失构建体比内含子-1完整构建体具有更高的TCDD诱导性。定量RT-PCR分析显示，CHX的内含子-1完整的构建体的超诱导水平大于内含子-1缺失的构建体。本研究结果表明，人CYP 1A 1基因的内部基因组序列，特别是内含子-1的内部序列，参与了超诱导CYP 1A 1基因的CHX。(c)2007爱思唯尔公司All rights reserved.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces CYP1A1 mRNA expression, and co-treatment with the protein synthesis inhibitor, cycloheximide (CHX) magnifies its expression severalfold further. Although this phenomenon has been reported as superinduction, its molecular mechanism is still obscure. In the present Study, we analyzed the influence of the CYP1A1 internal genomic sequence oil CHX-mediated superinduction. Partial sequences of the human CYP1A1 were inserted at the 5' end of the internal ribosomal entry site (IRES) connected to luciferase cDNA, and generated constructs were transiently transfected into CHO or HcpG2 cells. Intron-1 deletion constructs showed higher inductivity than intron-1 intact constructs by TCDD. Quantitative RT-PCR analyses revealed that the super-induced levels by CHX of the intron-1 intact constructs were greater than those of the intron-1 deletion constructs. The present results indicate that internal genomic sequences of the human CYP1A1 gene, especially the internal sequence of intron-1, are involved in superinduction of the CYP1A1 gene by CHX. (c) 2007 Elsevier Inc. All rights reserved.