Tissue- and cell type-specific expression of cytochrome P450 1A1 and cytochrome P450 1A2 mRNA in the mouse localized in situ hybridization

Tissue- and cell type-specific expression of cytochrome P450 1A1 and cytochrome P450 1A2 mRNA in the mouse localized in situ hybridization
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DOI:
10.1016/s0006-2952(99)00110-0
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发表时间:
1999-08-01
影响因子:
5.8
通讯作者:
Nebert, DW
Nebert, DW
中科院分区:
医学2区
文献类型:
--
作者:
Dey, A;Jones, JE;Nebert, DW

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我们使用原位杂交检测器官和细胞类型特异性组成和3-甲基胆蒽(3 MC)诱导的细胞色素P450(CYP)1A 1和CYP 1A 2 mRNA表达在C57 BL/6 N小鼠的各种组织。在小鼠接受腹膜内3 MC或单独载体后10小时进行原位杂交。我们检测了3 MC诱导的CYP 1A 1 mRNA水平:肝脏(小叶中心,比门静脉周围区域更明显);肺(Clara II型细胞比I型上皮细胞多得多);脑,尤其是内皮细胞,排列在脉络丛的血管表面;消化道(十二指肠>空肠>回肠>结肠>食管>胃-特别是绒毛上皮,加上固有层中腺体周围的细胞);肾的肾小体;卵巢(髓质比皮质更容易);以及整个动物的血管内皮细胞。在这些组织中,通过原位杂交检测不到组成型CYP 1A 1 mRNA。相比之下,在肝脏中可测量组成型CYP 1A 2 mRNA,仅在肝脏、肺和十二指肠(细胞类型位置与CYP 1A 1相似)中观察到3 MC诱导型CYP 1A 2 mRNA;上述其他组织的CYP 1A 2 mRNA为阴性。这些数据表明,小鼠Cypla亚家族的两个成员之间的组织和细胞类型特异性表达的显着差异。由于3 MC诱导的CYP 1A 1在整个动物中无处不在,而不仅仅是“入口”,这些结果支持我们的假设,即CYP 1A 1,由各种组织和细胞类型中的特定内源性信号诱导,可能参与一个或多个关键的生命过程-除了其公认的多环烃代谢作用外,某些药物,和其他(C)1999年爱思唯尔科学公司
We used in situ hybridization to examine organ- and cell type specific constitutive and 3-methylcholanthrene (3MC)-inducible cytochrome P450 (CYP)1A1 and CYP1A2 mRNA expression in Various tissues of the C57BL/6N mouse. In situ hybridization was carried out 10 hr after the mice had received intraperitoneal 3MC, or vehicle alone. We detected levels of 3MC induced CYP1A1 mRNA in: liver (centrilobular, more so than periportal, regions); lung (Clara Type II cells much more than Type I epithelial cells); brain, especially endothelial cells Lining the vascular surface of the choroid plexus; the digestive tract (duodenum > jejunum > ileum > colon > esophagus > stomach-in particular, the villous epithelium, plus cells surrounding glands in the lamina propria); renal corpuscles of the kidney; the ovary (medulla more so than cortex); and the endothelial cells of blood vessels throughout the animal. Constitutive CYP1A1 mRNA was not detectable by in situ hybridization in any of these tissues. In contrast, constitutive CYP1A2 mRNA was measurable in liver, and 3MC-inducible CYP1A2 mRNA was observed only in liver, lung, and duodenum (having cell-type locations similar to those of CYP1A1); the other above-mentioned tissues were negative for CYP1A2 mRNA. These data demonstrate the striking differences in tissue- and cell type-specific expression between the two members of the mouse Cypla subfamily. Because of the ubiquitous nature of 3MC-inducible CYP1A1 throughout the animal rather than just "portals of entry," these results support our hypothesis that CYP1A1, induced by particular endogenous signals in various tissues and cell types, might participate in one or more critical life processes-in addition to its well-established role of metabolism of polycyclic hydrocarbons, certain drugs, and other (C) 1999 Elsevier Science Inc.