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[Label-free] 肝组织-Label free-药物代谢-泛素化-膜蛋白

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发表于 2016-1-26 14:57:56 | 显示全部楼层 |阅读模式

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J Proteome Res. 2015 Aug 7;14(8):3305-14. doi: 10.1021/acs.jproteome.5b00334. Epub 2015 Jul 20.
Comparative Proteomic Analysis of Human Liver Tissue and Isolated Hepatocytes with a Focus on Proteins Determining Drug Exposure.

IF=
14年4.245
13年5.001
12年5.056
11年5.113

研究关键词 肝组织,Label free,药物代谢,泛素化

研究概要  
图片.png

研究目的:
通过Label-free蛋白质组学研究人类肝细胞和肝脏组织,旨在确定药物运输、代谢和毒力对机体的影响。
研究结论:
通过定量蛋白组学,肝细胞中5144个膜蛋白被鉴定,表达量横跨个数量级。其中,有些膜蛋白在肝细胞中表达量比在肝脏组织中的表达量低,表明肝细胞产生氧化应激反应导致膜蛋白通过泛素化途径降解。
案例选取要点:
Label-free研究肝脏蛋白的案例,结合泛素化修饰分析,检测药物对肝脏的影响;
数据分析类型:常规差异蛋白组学生物信息分析。

Abstract
Freshly isolated human hepatocytes are considered the gold standard for in vitro studies of liver functions, including drug transport, metabolism, and toxicity. For accurate predictions of the in vivo outcome, the isolated hepatocytes should reflect the phenotype of their in vivo counterpart, i.e.,hepatocytes in human liver tissue. Here, we quantified and compared the membrane proteomes of freshly isolated hepatocytes and human liver tissueusing a label-free shotgun proteomics approach. A total of 5144 unique proteins were identified, spanning over 6 orders of magnitude in abundance. There was a good global correlation in protein abundance. However, the expression of many plasma membrane proteins was lower in the isolatedhepatocytes than in the liver tissue. This included transport proteins that determine hepatocyte exposure to many drugs and endogenous compounds. Pathway analysis of the differentially expressed proteins confirmed that hepatocytes are exposed to oxidative stress during isolation and suggested that plasma membrane proteins were degraded via the protein ubiquitination pathway. Finally, using pitavastatin as an example, we show how protein quantifications can improve in vitro predictions of in vivo liver clearance. We tentatively conclude that our data set will be a useful resource for improved hepatocyte predictions of the in vivo outcome.


KEYWORDS:
ADME proteins; CYP enzymes; UGT enzymes; drug transporters; human hepatocytes; in vitro−in vivo extrapolation; membrane proteome; oxidative stress; quantitative proteomics; total protein approach



免费全文链接
http://pubs.acs.org/doi/abs/10.1021/acs.jproteome.5b00334


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肝脏-label free-药物代谢 肝癌细胞HepG2 6标试验方案.pdf

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