Comparison of protein expression between human livers and the hepatic cell lines HepG2, Hep3B, and Huh7 using SWATH and MRM-HR proteomics: Focusing on drug-metabolizing enzymes.
Comparison of protein expression between human livers and the hepatic cell lines HepG2, Hep3B, and Huh7 using SWATH and MRM-HR proteomics: Focusing on drug-metabolizing enzymes.
复制标题
使用 SWATH 和 MRM-HR 蛋白质组学比较人肝脏与肝细胞系 HepG2、Hep3B 和 Huh7 之间的蛋白质表达：关注药物代谢酶。
DOI：
10.1016/j.dmpk.2018.03.003
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发表时间：
2018-04
影响因子：
2.1
通讯作者：
Zhu HJ
中科院分区：
文献类型：
--
作者：
Shi J;Wang X;Lyu L;Jiang H;Zhu HJ
人肝细胞系被广泛用作研究药物代谢和肝毒性的体外模型。然而，该模型的有效性仍然是一个争论的主题，因为细胞系中各种蛋白质的表达，包括药物代谢酶（DME），可能与人类肝脏中的蛋白质表达显著不同。在本研究中，我们首先进行了非靶向的蛋白质组学分析的微粒体的细胞系HepG 2，Hep 3B，和Huh 7，并比较它们与人类肝脏使用顺序窗口采集所有理论质谱（SWATH）方法。此外，高分辨率多反应监测（MRM-HR），靶向蛋白质组学的方法，被用来比较人类肝脏和细胞系之间的预选DME的表达。一般而言，SWATH定量与MRM-HR分析一致。在细胞和人类肝脏中定量了超过3，000种蛋白质组，人类肝脏的蛋白质组谱与细胞系显着不同。在用MRM-HR定量的101个DME中，大多数在细胞系中以显著较低的水平表达。因此，在使用这些细胞系进行肝脏药物代谢和毒性研究时必须谨慎。
Human hepatic cell lines are widely used as an in vitro model for the study of drug metabolism and liver toxicity. However, the validity of this model is still a subject of debate because the expressions of various proteins in the cell lines, including drug-metabolizing enzymes (DMEs), can differ significantly from those in human livers. In the present study, we first conducted an untargeted proteomics analysis of the microsomes of the cell lines HepG2, Hep3B, and Huh7, and compared them to human livers using a sequential window acquisition of all theoretical mass spectra (SWATH) method. Furthermore, high-resolution multiple reaction monitoring (MRM-HR), a targeted proteomic approach, was utilized to compare the expressions of preselected DMEs between human livers and the cell lines. In general, the SWATH quantifications were in good agreement with the MRM-HR analysis. Over 3,000 protein groups were quantified in the cells and human livers, and the proteome profiles of human livers significantly differed from the cell lines. Among the 101 DMEs quantified with MRM-HR, most were expressed at substantially lower levels in the cell lines. Thus, appropriate caution must be exercised when using these cell lines for the study of hepatic drug metabolism and toxicity.
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影响因子：
9.9
作者：
Lange, Vinzenz;Picotti, Paola;Domon, Bruno;Aebersold, Ruedi
通讯作者：
Aebersold, Ruedi
DOI：
10.1126/science.1260793
发表时间：
2015-02-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Battle A;Khan Z;Wang SH;Mitrano A;Ford MJ;Pritchard JK;Gilad Y
通讯作者：
Gilad Y
影响因子：
5.1
作者：
Jin, Cheng-Yun;Park, Cheol;Choi, Yung Hyun
通讯作者：
Choi, Yung Hyun
影响因子：
--
作者：
Manov, I;Hirsh, M;Iancu, TC
通讯作者：
Iancu, TC
影响因子：
4.4
作者：
Glatter, Timo;Ludwig, Christina;Schmidt, Alexander
通讯作者：
Schmidt, Alexander