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Induction of CYP3A4 by 1 alpha,25-dyhydroxyvitamin D-3 in HepG2 cells

机译：CYP3A4被HepG2细胞中的1 alpha，25-dyhydroxyvitamin D-3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. (C) 2003 Elsevier Science Inc. All rights reserved. [References: 27]
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是否在人肝癌细胞系HepG2细胞中调节CYP3A4基因表达。与对照培养相比，用1alpha，25-（OH）（2）D-3处理可诱导CYP3A4 mRNA和CYP3A4免疫反应蛋白分别诱导1.5倍和4.0倍的诱导，呈时间依赖性。这些观察结果与以前的报道一致，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）增加了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。 （C）2003 Elsevier Science Inc.保留所有权利。 [参考：27]

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