Quantitative analysis of cytochrome P450 isoforms in human liver microsomes by the combination of proteomics and chemical probe-based assay
文献类型：期刊论文
| 作者 | Liu, Xidong1,2; Hu, Lianghai1,2; Ge, Guangbo3; Yang, Bo1,2; Ning, Jing3; Sun, Shixin4; Yang, Ling3; Pors, Klaus5; Gu, Jingkai1,2 |
| 刊名 | proteomics
 |
| 出版日期 | 2014-08-01 |
| 卷号 | 14期号:16页码:1943-1951 |
| 关键词 | Biomedicine Cytochrome P450 MRM Protein quantification Stable isotope labeling |
| 通讯作者 | xidongliu ; 葛广波 ; jingkaigu |
| 英文摘要 | cytochrome p450 (cyp) is one of the most important drug-metabolizing enzyme families, which participates in the biotransformation of many endogenous and exogenous compounds. quantitative analysis of cyp expression levels is important when studying the efficacy of new drug molecules and assessing drug-drug interactions in drug development. at present, chemical probe-based assay is the most widely used approach for the evaluation of cyp activity although there are cross-reactions between the isoforms with high sequence homologies. therefore, quantification of each isozyme is highly desired in regard to meeting the ever-increasing requirements for carrying out pharmacokinetics and personalized medicine in the academic, pharmaceutical, and clinical setting. herein, an absolute quantification method was employed for the analysis of the seven isoforms cyp1a2, 2b6, 3a4, 3a5, 2c9, 2c19, and 2e1 using a proteome-derived approach in combination with stable isotope dilution assay. the average absolute amount measured from twelve human liver microsomes samples were 39.3, 4.3, 54.0, 4.6, 10.3, 3.0, and 9.3 (pmol/mg protein) for 1a2, 2b6, 3a4, 3a5, 2c9, 2c19, and 2e1, respectively. importantly, the expression level of cyp3a4 showed high correlation (r = 0.943, p < 0.0001) with the functional activity, which was measured using bufalin-a highly selective chemical probe we have developed. the combination of mrm identification and analysis of the functional activity, as in the case of cyp3a4, provides a protocol which can be extended to other functional enzyme studies with wide application in pharmaceutical research. |
| WOS标题词 | science & technology ; life sciences & biomedicine |
| 学科主题 | 物理化学 |
| 类目[WOS] | biochemical research methods ; biochemistry & molecular biology |
| 研究领域[WOS] | biochemistry & molecular biology |
| 关键词[WOS] | drug-drug interactions ; genetic polymorphisms ; mass-spectrometry ; hepatic microsomes ; rt-pcr ; cyp3a4 ; metabolism ; expression ; rat ; pharmacokinetics |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000340422000010 |
| 公开日期 | 2016-05-09 |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/144430]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 作者单位 | 1.Jilin Univ, Key Lab Mol Enzymol & Engn, Minist Educ, Changchun 130012, Peoples R China 2.Jilin Univ, Res Ctr Drug Metab, Sch Life Sci, Changchun 130012, Peoples R China 3.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian, Peoples R China 4.Appl Biosyst Inc, Asia Pacific Applicat Support Ctr, Shanghai, Peoples R China 5.Univ Bradford, Sch Life Sci, Inst Canc Therapeut, Bradford BD7 1DP, W Yorkshire, England |
| 推荐引用方式 GB/T 7714 | Liu, Xidong,Hu, Lianghai,Ge, Guangbo,et al. Quantitative analysis of cytochrome P450 isoforms in human liver microsomes by the combination of proteomics and chemical probe-based assay[J]. proteomics,2014,14(16):1943-1951. |
| APA | Liu, Xidong.,Hu, Lianghai.,Ge, Guangbo.,Yang, Bo.,Ning, Jing.,...&Gu, Jingkai.(2014).Quantitative analysis of cytochrome P450 isoforms in human liver microsomes by the combination of proteomics and chemical probe-based assay.proteomics,14(16),1943-1951. |
| MLA | Liu, Xidong,et al."Quantitative analysis of cytochrome P450 isoforms in human liver microsomes by the combination of proteomics and chemical probe-based assay".proteomics 14.16(2014):1943-1951. |
入库方式： OAI收割
来源：大连化学物理研究所
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