Takahashi Y, Nakayama K, Shimojima T, Itoh S, Kamataki T
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
Eur J Biochem. 1996 Dec 15;242(3):512-8. doi: 10.1111/j.1432-1033.1996.0512r.x.
Induction of aryl hydrocarbon hydroxylase by aryl hydrocarbons occurs only in neonatal rabbits and not in adult rabbits [Kahl, G. F., Friederich, D. E., Bigelow, S. W., Okey, A. B. & Nebert, D. W. (1980) Dev. Pharmacol. Ther. 1,137-162]. In the present study, we isolated cDNA clones encoding aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (Arnt) from adult rabbits. The deduced amino acid sequences of rabbit AhR and Arnt showed 80% and 94% identities with those of human AhR and Arnt, respectively. Rabbit AhR mRNA was predominantly expressed in the lung and liver. In contrast, rabbit Arnt mRNA was expressed at almost the same level in all tissues except for the heart, liver, and small intestine. Gel shift analysis showed that the AhR. Arnt complex could bind to the consensus xenobiotic-responsive element, which indicates that AhR expressed in adult rabbit liyers possessed binding activity to the consensus xenobiotic-responsive element in vitro, although aryl hydrocarbons did not induce the activity of AHH in adult rabbits. We propose that the incapability of adult rabbits to induce cytochrome P-450 1A1 (CYP1A1) is caused by factors other than AhR and Arnt.
芳烃对芳烃羟化酶的诱导作用仅发生在新生兔中,而在成年兔中则不会发生[卡尔,G.F.,弗里德里希,D.E.,比奇洛,S.W.,奥基,A.B. & 内伯特,D.W.(1980年)《发育药理学与治疗学》1,137 - 162]。在本研究中,我们从成年兔中分离出了编码芳烃受体(AhR)和芳烃受体核转运蛋白(Arnt)的cDNA克隆。推导的兔AhR和Arnt的氨基酸序列与人类AhR和Arnt的氨基酸序列分别具有80%和94%的同一性。兔AhR mRNA主要在肺和肝脏中表达。相比之下,兔Arnt mRNA在除心脏、肝脏和小肠之外的所有组织中表达水平几乎相同。凝胶迁移分析表明,AhR - Arnt复合物能够结合共有外源性物质反应元件,这表明成年兔肝脏中表达的AhR在体外对共有外源性物质反应元件具有结合活性,尽管芳烃不会诱导成年兔中AHH的活性。我们提出成年兔无法诱导细胞色素P - 450 1A1(CYP1A1)是由AhR和Arnt以外的因素引起的。