Department of Pharmacy, Shinshu University Hospital, Matsumoto, Japan.
Drug Metab Pharmacokinet. 2012;27(6):598-604. doi: 10.2133/dmpk.dmpk-12-rg-017. Epub 2012 May 29.
There is a great deal of interest in differentiation of human embryonic stem cells (hESCs) into hepatocyte-like cells for application in pharmaceutical screening. Cytochrome P450 (CYP) 1A is involved in the metabolic activation of procarcinogenic compounds as well as in detoxification of drugs. We differentiated hESCs into hepatocyte-like cells (hESC-derived hepatocyte-like cells) and examined whether CYP1A was induced in these cells by typical inducers of CYP1A. hESC-derived hepatocyte-like cells expressed albumin, α-fetoprotein, CYP3A4, CYP3A7, CYP1A1, CYP1A2, and UDP-glucuronyl transferase (UGT) 1A1 mRNA. The levels of CYP1A1, CYP1A2, and UGT1A1 mRNA expression were increased by omeprazole and 3-methylcholanthrene. Furthermore, the enzyme activity of CYP1A was also increased by these compounds. In conclusion, hESC-derived hepatocyte-like cells are available for the detection of CYP1A inducers.
人们对将人胚胎干细胞 (hESC) 分化为肝样细胞以应用于药物筛选非常感兴趣。细胞色素 P450 (CYP) 1A 参与前致癌化合物的代谢激活以及药物的解毒。我们将 hESC 分化为肝样细胞 (hESC 衍生的肝样细胞)，并研究这些细胞中 CYP1A 是否被 CYP1A 的典型诱导剂诱导。hESC 衍生的肝样细胞表达白蛋白、α-胎蛋白、CYP3A4、CYP3A7、CYP1A1、CYP1A2 和 UDP-葡糖醛酸基转移酶 (UGT) 1A1 mRNA。奥美拉唑和 3-甲基胆蒽可增加 CYP1A1、CYP1A2 和 UGT1A1 mRNA 的表达水平。此外，这些化合物还增加了 CYP1A 的酶活性。总之，hESC 衍生的肝样细胞可用于检测 CYP1A 诱导剂。
