Glucocorticoid receptor contributes to the altered expression of hepatic cytochrome P450 upon cigarette smoking
Glucocorticoid receptor contributes to the altered expression of hepatic cytochrome P450 upon cigarette smoking
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DOI：
10.3892/mmr.2016.5898
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发表时间：
2016-12-01
影响因子：
3.4
通讯作者：
Chen, Huaiyong
中科院分区：
文献类型：
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作者：
Li, Xue;Yan, Zhongfang;Chen, Huaiyong
吸烟已被证明会引起肝脏的病理改变。然而，在吸烟引起的炎症中，肝脏代谢是如何改变的仍有待完全阐明。本研究通过建立大鼠吸烟模型，探讨吸烟对肝脏炎症、自噬活性、核受体和CYP表达的影响。吸烟暴露大鼠肝脏中白细胞介素1 β表达升高和自噬激活。吸烟诱导细胞色素mRNA表达水平显著降低，包括细胞色素P450 (Cyp)1A2、Cyp2D4和Cyp3A2。因此，Cyp表达的调节因子糖皮质激素受体（GR）也出现了下降。GR信号在人肝LO2细胞中的激活不影响自噬基因，但可导致hCYP1A2、hCYP2C19和hCYP3A4上调，hCYP2C9下调。GR拮抗剂RU486消除了这种影响，提示GR在吸烟后肝脏代谢中的重要性。
Cigarette smoking has been shown to cause pathological alterations in the liver. However, how hepatic metabolism is altered during cigarette smoking-induced inflammation remains to be fully elucidated. In the present study, a rat model of smoking was established to examine the effects of cigarette smoking on inflammation, autophagy activity, and the expression of nuclear receptor and CYP in the liver. Elevated expression of interleukin 1 beta and activation of autophagy in the liver were observed upon smoking exposure in rats. Cigarette smoking induced a significant reduction in the mRNA expression levels of cytochromes, including cytochrome P450 (Cyp)1A2, Cyp2D4 and Cyp3A2. Accordingly, a decrease was also observed in glucocorticoid receptor (GR), a regulator of the expression of Cyp. Activation of the GR signal in human hepatic LO2 cells did not affect autophagic genes, however, it led to the upregulation of hCYP1A2, hCYP2C19 and hCYP3A4, and the downregulation of hCYP2C9. The GR antagonist, RU486, eliminated this effect, suggesting the importance of GR in liver metabolism upon cigarette smoking.