Comprehensive and quantitative proteome profiling of the mouse liver and plasma
Comprehensive and quantitative proteome profiling of the mouse liver and plasma
复制标题
DOI：
10.1002/hep.22123
复制
发表时间：
2008-03-01
期刊：
影响因子：
13.5
通讯作者：
Beretta, Laura
中科院分区：
文献类型：
--
作者：
Lai, Keane K. Y.;Kolippakkam, Deepak;Beretta, Laura
我们报告了小鼠肝脏和血浆蛋白质组的全面定量分析。所使用的方法基于完整蛋白质的广泛分级、根据蛋白质的丰度和大小进一步分离蛋白质以及高精度质谱分析。该分析达到了哺乳动物组织或生物液体蛋白质组分析的深度，迄今为止尚未报道过，在肝脏和相应血浆中分别以高置信度鉴定出 7099 和 4727 种蛋白质。该方法可以在两个区室中鉴定低丰度蛋白质，例如细胞因子、趋化因子和受体，并可以检测血浆中 pg/mL 浓度范围内的蛋白质。该方法还允许对所有已鉴定的蛋白质进行半定量。计算出的丰度分数与肝脏中鉴定的大多数蛋白质的相应转录本的丰度相关。最后，肝脏和血浆数据集的比较表明，可以在血浆中检测到肝脏中鉴定的大量蛋白质。这些包括参与补体和凝血、脂肪酸、嘌呤和丙酮酸代谢、糖异生和糖酵解、蛋白质泛素化以及胰岛素、白细胞介素 4、表皮生长因子和血小板衍生生长因子信号传导的蛋白质。结论：对小鼠肝脏和相应血浆蛋白质组的深入分析为利用小鼠肝脏疾病模型进行肝脏病理学和生物学研究提供了坚实的基础，以更好地了解、诊断、治疗和预防人类肝脏疾病。
We report a comprehensive and quantitative analysis of the mouse liver and plasma proteomes. The method used is based on extensive fractionation of intact proteins, further separation of proteins based on their abundance and size, and high-accuracy mass spectrometry. This analysis reached a depth in proteomic profiling not reported to date for a mammalian tissue or a biological fluid, with 7099 and 4727 proteins identified with high confidence in the liver and in the corresponding plasma, respectively. This method allowed for the identification in both compartments of low-abundance proteins such as cytokines, chemokines, and receptors and for the detection in plasma of proteins in the pg/mL concentration range. This method also allowed for semiquantitation of all identified proteins. The calculated abundance scores correlated with the abundance of the corresponding transcripts for the large majority of the proteins identified in the liver. Finally, comparison of the liver and plasma datasets demonstrated that a significant number of proteins identified in the liver can be detected in plasma. These included proteins involved in complement and coagulation, in fatty acid, purine and pyruvate metabolism, in gluconeogenesis and glycolysis, in protein ubiquitination, and in insulin, interleukin-4, epidermal growth factor, and platelet-derived growth factor signaling. Conclusion: This in-depth analysis of the mouse liver and corresponding plasma proteomcs provides a strong basis for investigations of liver pathobiology and biology that employ mouse models of hepatic diseases in an effort to better understand, diagnose, treat, and prevent human hepatic diseases.