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首页> 外文期刊>Life sciences >Induction of CYP3A4 by 1alpha,25-dyhydroxyvitamin D3 in HepG2 cells.
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Induction of CYP3A4 by 1alpha,25-dyhydroxyvitamin D3 in HepG2 cells.

机译：在HepG2细胞中1alpha，25-dyhydroxyvitamin D3对CYP3A4的诱导。

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摘要

CYP3A4, the predominant cytochrome P450 (CYP) expressed in human liver, contributes to the metabolism of approximately half the drugs in use today. In general, human-derived cell lines fail to express CYPs. It was previously shown that CYP3A4 mRNA and CYP3A immunoreactive protein are induced by 1alpha,25-dyhydroxyvitamin D(3) (1alpha,25-(OH)(2)D(3)) in the human colon carcinoma cell line Caco-2. The aim of the present study was to examine whether 1alpha,25-(OH)(2)D(3) regulates CYP3A4 gene expression in HepG2 cells, a human hepatocarcinoma cell line. Treatment with 1alpha,25-(OH)(2)D(3) resulted in an induction of CYP3A4 mRNA and CYP3A4 immunoreactive protein, 1.5-fold and 4.0-fold respectively, when compared to control cultures, in a time-dependent fashion. These observations are in agreement with previous reports suggesting a role of 1alpha,25-(OH)(2)D(3) on CYP3A4 transcription regulation, and demonstrate that this hormone, as in Caco-2 cells, increase CYP3A4 levels in HepG2 cells. In conclusion, HepG2 cell cultures treated with 1alpha,25-(OH)(2)D(3), provides a useful model to study the function of CYP3A4 and its role in drug liver metabolism.
机译：CYP3A4是在人类肝脏中表达的主要细胞色素P450（CYP），它有助于当今使用的大约一半药物的代谢。通常，人源细胞系不能表达CYP。先前显示CYP3A4 mRNA和CYP3A免疫反应蛋白是由人结肠癌细胞系Caco-2中的1alpha，25-dyhydroxyvitamin D（3）（1alpha，25-（OH）（2）D（3））诱导的。本研究的目的是检查1alpha，25-（OH）（2）D（3）是否调节人肝癌细胞系HepG2细胞中的CYP3A4基因表达。用1alpha，25-（OH）（2）D（3）处理导致CYP3A4 mRNA和CYP3A4免疫反应蛋白的诱导，与对照培养物相比，呈时间依赖性，分别为1.5倍和4.0倍。这些观察结果与以前的报告一致，表明1alpha，25-（OH）（2）D（3）在CYP3A4转录调控中的作用，并证明这种激素（如在Caco-2细胞中一样）会增加HepG2细胞中的CYP3A4水平。总之，用1alpha，25-（OH）（2）D（3）处理的HepG2细胞培养物为研究CYP3A4的功能及其在药物肝代谢中的作用提供了有用的模型。

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