Elizondo Guillermo, Medina-Díaz Irma M
Sección Externa de Toxicología, CINVESTAV-IPN, P.O. Box 14-740, México, D.F. 07000, Mexico.
Life Sci. 2003 May 30;73(2):141-9. doi: 10.1016/s0024-3205(03)00262-5.
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.
细胞色素P450 3A4（CYP3A4）是人类肝脏中表达的主要细胞色素P450（CYP），参与了当今约一半在用药物的代谢过程。一般来说，源自人类的细胞系无法表达细胞色素P450。此前研究表明，在人结肠癌细胞系Caco-2中，1α,25-二羟基维生素D3（1α,25-(OH)2D3）可诱导CYP3A4信使核糖核酸（mRNA）和CYP3A免疫反应性蛋白的表达。本研究的目的是检测1α,25-(OH)2D3是否能调节人肝癌细胞系HepG2细胞中CYP3A4基因的表达。与对照培养物相比，用1α,25-(OH)2D3处理后，CYP3A4 mRNA和CYP3A4免疫反应性蛋白呈时间依赖性诱导，分别增加了1.5倍和4.0倍。这些观察结果与之前关于1α,25-(OH)2D3在CYP3A4转录调控中作用的报道一致，并表明这种激素与在Caco-2细胞中一样，可增加HepG2细胞中CYP3A4的水平。总之，用1α,25-(OH)2D3处理的HepG2细胞培养物为研究CYP3A4的功能及其在药物肝脏代谢中的作用提供了一个有用的模型。
