Primary structure and organ-specific expression of the rat aryl hydrocarbon receptor repressor gene
Primary structure and organ-specific expression of the rat aryl hydrocarbon receptor repressor gene
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DOI：
10.1248/bpb.29.640
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发表时间：
2006-04-01
影响因子：
2
通讯作者：
Inouye, Y
中科院分区：
文献类型：
--
作者：
Nishihashi, H;Kanno, Y;Inouye, Y
芳烃受体阻遏物 (AhRR) 是转录因子基本螺旋-环-螺旋/Per-Arnt-Sim (bHLH/PAS) 家族的成员，通过 AhR 介导的外源或内源配体依赖性信号转导提供负反馈环。我们对 24 小时前腹腔注射 3-甲基胆蒽 (3-MC) 的雄性 Wistar 大鼠心脏中提取的全长 AhRR mRNA 进行了测序。 95.6 kb 长的 AhRR 基因组被阐明由 11 个外显子和 10 个内含子组成。与女性相比，AhRR mRNA 的组成型表达在男性中显着，与 AhR 表达的性别差异平行。尽管 AhRR 在所有测试的组织中普遍表达，但 AhRR 表达水平在小肠中较高，其中 3-MC 依赖性 CYP1A1 转录诱导作用不如心脏、肺、肝脏和肾脏中显着。在用 AhRR 表达质粒与报告质粒瞬时转染的大鼠肝源性 RL-34 细胞中，观察到在存在和不存在 3-MC 的情况下，AhR 依赖性转录激活的剂量依赖性抑制。
The aryl hydrocarbon receptor repressor (AhRR) is a member of the basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) family of transcription factors, providing a negative feedback loop with a xenobiotic or endogenous ligand-dependent signal transduction mediated by the AhR. We sequenced full-length AhRR mRNA extracted from the heart of a male Wistar rat injected intraperitoneally with 3-methylcholanthrene (3-MC) 24h before. The 95.6 kb-long AhRR genome was clarified to consist of 11 exons and 10 introns. The constitutive expression of AhRR mRNA was prominent in males when compared with females in parallel with the sexual difference in AhR expression. Although AhRR was ubiquitously expressed in all tissues tested, the levels of AhRR expression were higher in the small intestine, where the 3-MC-dependent induction of CYP1A1 transcription was less significant, than in the heart, lung, liver, and kidney. The dose-dependent suppression of AhR-dependent transcriptional activation in both the presence and absence of 3-MC was observed in rat liver-derived RL-34 cells transiently transfected with the expression plasmid for AhRR in combination with the reporter plasmid.