Expression and inducibility of CYP1A1, 1A2, 1B1 by β-naphthoflavone and CYP2B22, 3A22, 3A29, 3A46 by rifampicin in the respiratory and olfactory mucosa of pig
Expression and inducibility of CYP1A1, 1A2, 1B1 by β-naphthoflavone and CYP2B22, 3A22, 3A29, 3A46 by rifampicin in the respiratory and olfactory mucosa of pig
复制标题
DOI：
10.1016/j.tox.2009.03.003
复制
发表时间：
2009-06-16
期刊：
影响因子：
4.5
通讯作者：
Gervasi, P. G.
中科院分区：
文献类型：
--
作者：
Messina, A.;Nannelli, A.;Gervasi, P. G.
特定CYP的存在和诱导（1A 1、1A 2、1B 1、2B 22、3A 22、3A 29和3A 46）和相关转录因子在对照和β-萘酮（β NF）处理的猪的肝脏、呼吸道和嗅觉粘膜中，在活性和/或转录水平上研究了AhR、CAR、PXR和HNF 4 α（AhR、CAR、PXR和HNF 4 α）的激动剂或利福平（RIF），PXR激动剂荧光定量PCR结果显示，ONE对肝脏、呼吸道和嗅觉组织中的CYP 1A 1 mRNA有不同程度的增强作用，而对肝脏中的CYP 1A 2和1B 1 mRNA有增强作用。因此，在两种鼻组织的微粒体中，CYP 1A 1的转录激活伴随着乙氧基试卤灵脱乙基酶活性（该亚型的标志物）的诱导，但不伴随甲氧基试卤灵脱甲基酶活性（CYP 1A 2的标志物）的诱导。利福平处理导致肝脏中CYP 2B 22和CYP 3As基因的转录激活，但在呼吸道和嗅觉粘膜中不激活。同时，CYP 2B（乙氧基4-（三氟甲基）香豆素脱乙基酶）和CYP 3A（6 β-睾酮羟化酶和苄氧基喹啉脱苄酶）的标记活性在肝微粒体中诱导，但在鼻微粒体中未诱导。考虑到转录因子，发现AhR mRNA的基础表达在肝脏中与在两个鼻组织中一样高，但不容易被ONE诱导。此外，发现除了肝脏之外，PXR mRNA在鼻组织中表达良好，而CAR和HNF 4 α mRNA几乎未检测到。在任何情况下，这些成绩单似乎是通过RIF治疗增强。我们的研究结果表明，在猪的呼吸和嗅觉粘膜中，虽然AhR的存在，但只有CYP 1A 1，而不是1A 2和1B 1导致被β NF诱导。同样，在这些鼻组织中观察到，尽管存在PXR，但RIF均不能诱导CYP 2B 22或任何CYP 3A。因此，鼻粘膜中CYP 1A 2、1B 1、2B 22、3A 22、3A 29和3A 46的调节机制涉及除了肝脏中基本的AhR、CAR、PXR和HNF 4 α以外的组织富集的转录因子。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
The presence and inducibility of specific CYPs (1A1, 1A2, 1B1, 2B22, 3A22, 3A29 and 3A46) and the related transcriptional factors (AhR, CAR, PXR, and HNF4 alpha) were investigated, at activity and/or transcriptional level, in liver, respiratory and olfactory mucosa of control and P-naphthoflavone (beta NF)-treated pigs an agonist of AhR, or rifampicin (RIF), an agonist of PXR. Experiments with real-time PCR showed that CYP1A1 mRNA was enhanced by ONE although at different extent, in liver, respiratory and olfactory tissues, whereas mRNAs of CYP1A2 and 1B1 were increased only in liver. Accordingly, in microsomes of both nasal tissues, the transcriptional activation of CYP1A1 was accompanied by an induction of ethoxyresorufin deethylase activity (a marker of this isoform) but not of methoxyresorufin demethylase activity (a marker of CYP1A2). The rifampicin treatment resulted in a transcriptional activation of CYP2B22 and CYP3As genes in liver but not in respiratory and olfactory mucosa. In parallel, the marker activity of CYP2B (ethoxy 4-(trifluoromethyl)coumarin deethylase) and CYP3As (6 beta-testosterone hydroxylase and benzyloxyquinoline debenzylase) were induced in liver microsomes but not in the nasal ones. Considering the transcriptional factors, the basal expression of AhR mRNA was found to be as high in liver as in both nasal tissues but not susceptible to induction by ONE Also PXR mRNA was found, aside liver, well expressed in the nasal tissues, whereas CAR and HNF4 alpha mRNAs were barely detected. In any case, these transcripts appeared to be enhanced by RIF treatment. Our results demonstrated that in the respiratory and olfactory mucosa of pig, although the presence of AhR, only CYP1A1, but not 1A2 and 1B1 resulted to be inducible by beta NF. Similarly, it was observed that in these nasal tissues, although the presence of PXR, neither CYP2B22 nor any CYP3A resulted to be inducible by RIF. Thus, the regulation mechanism of CYP1A2, 1B1, 2B22, 3A22, 3A29, and 3A46, in the nasal mucosa involves tissue-enriched transcriptional factors others than AhR, CAR, PXR, and HNF4 alpha, which are fundamental in liver. (C) 2009 Elsevier Ireland Ltd. All rights reserved.