Identification of genes controlled by the pregnane X receptor by microarray analysis of mRNAs from pregnenolone 16α-carbonitrile-treated rats
Identification of genes controlled by the pregnane X receptor by microarray analysis of mRNAs from pregnenolone 16α-carbonitrile-treated rats
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DOI：
10.1093/toxsci/kfl116
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发表时间：
2006-12-01
影响因子：
3.8
通讯作者：
Guzelian, Philip S.
中科院分区：
文献类型：
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作者：
Guzelian, Jeffrey;Barwick, Joyce L.;Guzelian, Philip S.
哺乳动物肝脏含有一种甾烷X受体（PXR，NR1I2），它结合药物和其他外源性物质，并刺激（或抑制）参与代谢消除外源化合物和一些有毒内源性物质的许多基因的表达。在本研究中，我们使用微阵列分析，以确定其在大鼠肝脏中的表达显着改变的双烯醇酮16 α-甲腈（PCN）治疗的基因。PCN是一种合成类固醇，可诱导细胞色素P4503A表达，并通过增加对后续应激损伤的抵抗力来保护肝脏。138个基因被显著诱导，而82个基因的表达被显著抑制。我们发现了已知由PCN诱导的基因的诱导，例如参与药物代谢和运输的酶。此外，许多基因的差异表达，其功能涉及细胞内代谢，运输的必需小分子，细胞周期，氧化还原平衡。我们的研究结果支持了这样一种观点，即PXR控制的基因网络的结构域可能比目前认为的更广泛，并且可能扩展到除了异生物质代谢之外的功能。
Mammalian liver contains a pregnane X receptor (PXR, NR1I2), which binds drugs and other xenobiotics, and stimulates (or suppresses) expression of numerous genes involved in the metabolic elimination of foreign compounds and some toxic endogenous substances. In the present study, we used microarray analysis to identify genes whose expression in rat liver was significantly altered by pregnenolone 16 alpha-carbonitrile (PCN) treatment. PCN is a synthetic steroid that induces cytochrome P4503A expression and is hepatoprotective by increasing resistance to subsequent stressful insults. Significant induction was seen for 138 genes while expression of 82 genes was significantly repressed. We found induction of genes known to be induced by PCN, such as enzymes involved in drug metabolism and transport. In addition, many genes were differentially expressed whose functions concerned intracellular metabolism, transport of essential small molecules, cell cycle, and redox balance. Our results support the idea that the domain of PXR-controlled gene networks may be even more extensive than currently thought and may extend to functions apart from xenobiotic metabolism.