细胞色素P450酶的表观遗传学调控及研究进展-中国现代应用药学.PDF

·综 述 · 细胞色素 P450 酶的表观遗传学调控及研究进展  1 1 1 1 1 2 1* 张轶雯 ，方罗 ，郑小卫 ，李清林 ，童莹慧 ，鲍美华 ，黄萍 (1.浙江省肿瘤医院药剂科，杭州 310022 ；2.长沙 医学院，长沙 410219) 摘要：细胞色素P450(CYPs) 家族是体内重要的药物代谢酶，其功能主要是代谢临床药物及外源性物质。长期以来，CYP450 酶的个体间功能活性差异往往被认为是由基因多态性所导致。然而随着研究的日益深入，人们发现基因序列的改变并不 能完全解释CYP450 酶的个体间活性差异。表观遗传学作为研究DNA 序列未发生变化而基因表达发生可遗传变异的学科， 可作为重要研究手段进一步解释 CYP450 酶的个体差异。该学科主要研究内容包括 DNA 甲基化、组蛋白翻译后修饰和 RNA 编辑等。本文就各主要CYP450 酶的表观遗传学调控研究进行综述并讨论其在药物代谢和临床应用中的意义。 关键词：细胞色素P450 酶；表观遗传学；调控；代谢 中图分类号：R284.1 文献标志码：A 文章编号：1007-7693(2017)02-0293-05 DOI: 10.13748/ki.issn1007-7693.2017.02.031 Study Advance on Epigenetic Regulation of Cytochrome P450 Enzymes 1 1 1 1 1 2 ZHANG Yiwen , FANG Luo , ZHENG Xiaowei , LI Qinglin , TONG Yinghui , BAO Meihua , HUANG 1* Ping (1.Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou 310022, China; 2.Changsha Medical University, Changsha 410219, China) ABSTRACT: The cytochromes P450 (CYPs) are a family of drug-metabolizing enzymes, which are responsible for the major part of metabolism of clinically important drugs and xenobiotic substances. The high interindividual variability in CYP450 expression and activity is used attributed to gene polymorphism, while it can not explain all the variability. Epigenetics is the study of cellular and physiological phenotypic trait variations that are due to external factors that switch genes on and off and affect how cells read genes. Unlike genetics based on changes to the DNA sequence (the genotype), the changes in gene expression or cellular phenotype, these changes include histone proteins post-translational modification, DNA methylation and miRNAs. In this review, we summ