Comparative proteome analyses of human plasma following in vivo lipopolysaccharide administration using multidimensional separations coupled with tandem mass spectrometry

Comparative proteome analyses of human plasma following in vivo lipopolysaccharide administration using multidimensional separations coupled with tandem mass spectrometry
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DOI:
10.1002/pmic.200400942
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发表时间:
2005-02-01
期刊:
影响因子:
3.4
通讯作者:
Smith, RD
Smith, RD
中科院分区:
生物学3区
文献类型:
--
作者:
Qian, WJ;Jacobs, JM;Smith, RD

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由于其提供适用于临床诊断和治疗的生物标志物以及更好地了解人类疾病的潜力,因此对人血浆蛋白质组的表征具有重大意义。我们在这里描述了一种策略,比较蛋白质组分析的人血浆,这是适用于生物标志物鉴定各种疾病状态。多维液相色谱-质谱(LC-MS/MS)已被应用于比较蛋白质组分析的血浆样品从一个人之前和9小时后脂多糖(LPS)管理。肽峰面积和每种蛋白质的肽鉴定数用于评价LC-MS/MS的再现性,并比较LPS处理后样品之间蛋白质浓度的相对变化。总共有804种不同的血浆蛋白(不包括免疫球蛋白)被确信地鉴定为32种蛋白质,观察到在LPS施用后浓度显著增加,包括几种已知的炎症反应或急性期介质,例如C-反应蛋白、血清淀粉样蛋白A和A2、LPS结合蛋白、LPS反应性和米色样锚蛋白、肝细胞生长因子激活剂、和血管性血友病因子,并因此构成炎症反应的潜在生物标志物。
There is significant interest in characterization of the human plasma proteome due to its potential for providing biomarkers applicable to clinical diagnosis and treatment and for gaining a better understanding of human diseases. We describe here a strategy for comparative proteome analyses of human plasma, which is applicable to biomarker identifications for various disease states. Multidimensional liquid chromatography-mass spectrometry (LC-MS/MS) has been applied to make comparative proteome analyses of plasma samples from an individual prior to and 9 h after lipopolysaccharide (LPS) administration. Peptide peak areas and the number of peptide identifications for each protein were used to evaluate the reproducibility of LC-MS/MS and to compare relative changes in protein concentration between the samples following LPS treatment. A total of 804 distinct plasma proteins (not including immunoglobulins) were confidently identified with 32 proteins observed to be significantly increased in concentration following LPS administration, including several known inflammatory response or acute-phase mediators such as C-reactive protein, serum amyloid A and A2, LPS-binding protein, LPS-responsive and beige-like anchor protein, hepatocyte growth factor activator, and von Willebrand factor, and thus, constituting potential biomarkers for inflammatory response.