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学科主题临床医学
Overexpression of CYP3A5 attenuates inducibility and activity of CYP3A4 in HepG2 cells
Kuang, Zemin1; Huang, Zhijun2,3; Li, Ying2,3; Yang, Guoping2,3; Liu, Meilin4; Yuan, Hong2,3
关键词Cyp3a4 Cyp3a5 Dexamethasone Inducibility Pharmacokinetic
刊名MOLECULAR MEDICINE REPORTS
2015-04-01
DOI10.3892/mmr.2014.3022
11期:4页:2868-2874
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology ; Medicine, Research & Experimental
研究领域[WOS]Oncology ; Research & Experimental Medicine
关键词[WOS]PREGNANE-X-RECEPTOR ; PRIMARY HUMAN HEPATOCYTES ; IN-VITRO ; BLOOD-PRESSURE ; TACROLIMUS PHARMACOKINETICS ; TRANSPLANT RECIPIENTS ; DRUG-INTERACTIONS ; CYTOCHROMES P450 ; GENE-EXPRESSION ; DOWN-REGULATION
英文摘要

There have been conflicting reports regarding the catalytic role of cytochrome P450 (CYP)3A5, which range from deeming it irrelevant to suggesting it is equally as important as CYP3A4, the most potent and abundant catalytic cytochrome enzyme in the human liver. This was partially attributed to the fact that CYP3A5 is highly polymorphic. However the importance of other underlying mechanisms remain unclear. The aim of the present study was to investigate the interaction between these enzymes. A human HepG2 hepatocellular line stably overexpressing CYP3A5 was constructed. The results suggested that CYP3A5 does not affect CYP3A4 expression directly. However, overexpression of CYP3A5 attenuated the inducibility of CYP3A4 in response to dexamethasone. A luciferase reporter assay indicated that this attenuation was due to a decrease in CYP3A4 promoter activity. Furthermore, a pharmacokinetic assay using quinidine and amlodipine showed that CYP3A4 enzyme activity per mg of microsomal protein was also decreased in the group overexpressing CYP3A5 compared with the dexamethasone-induced control group. In conclusion, the current study demonstrated that CYP3A5 may affect CYP3A4 at the transcriptional level and may thus modify CYP3A4 expression and activity in the presence of substrates and inducers. The results indicate that CYPs may interact with each other under certain conditions and that this interaction may be a novel mechanism by which drug-drug interactions are mediated.

语种英语
WOS记录号WOS:000351711100070
项目编号2011CB512001 ; 2012BAI37B05 ; 81273594 ; 2012zzts036
资助机构National Basic Research Program of China ; National Key Technology RD Program ; National Natural Science Foundation of China ; Fundamental Research Funds for the Central Universities of Central South University
引用统计
被引频次:2[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55564
专题北京大学第一临床医学院_老年病内科
作者单位1.Human Res Ctr Hypertens, Changsha 410013, Hunan, Peoples R China
2.Capital Med Univ, Dept Hypertens, Beijing Anzhen Hosp, Beijing 100029, Peoples R China
3.Cent S Univ, Xiangya Hosp 3, Ctr Clin Pharmacol, Changsha 410013, Hunan, Peoples R China
4.Peking Univ, Hosp 1, Dept Geriatr, Beijing 100034, Peoples R China
推荐引用方式
GB/T 7714
Kuang, Zemin,Huang, Zhijun,Li, Ying,et al. Overexpression of CYP3A5 attenuates inducibility and activity of CYP3A4 in HepG2 cells[J]. MOLECULAR MEDICINE REPORTS,2015,11(4):2868-2874.
APA Kuang, Zemin,Huang, Zhijun,Li, Ying,Yang, Guoping,Liu, Meilin,&Yuan, Hong.(2015).Overexpression of CYP3A5 attenuates inducibility and activity of CYP3A4 in HepG2 cells.MOLECULAR MEDICINE REPORTS,11(4),2868-2874.
MLA Kuang, Zemin,et al."Overexpression of CYP3A5 attenuates inducibility and activity of CYP3A4 in HepG2 cells".MOLECULAR MEDICINE REPORTS 11.4(2015):2868-2874.
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