Top-down quantitative proteomics identified phosphorylation of cardiac troponin I as a candidate biomarker for chronic heart failure.
Top-down quantitative proteomics identified phosphorylation of cardiac troponin I as a candidate biomarker for chronic heart failure.
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DOI：
10.1021/pr200258m
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发表时间：
2011-09-02
影响因子：
4.4
通讯作者：
Ge, Ying
中科院分区：
文献类型：
--
作者：
Zhang, Jiang;Guy, Moltu J.;Norman, Holly S.;Chen, Yi-Chen;Xu, Qingge;Dong, Xintong;Guner, Huseyin;Wang, Sijian;Kohmoto, Takushi;Young, Ken H.;Moss, Richard L.;Ge, Ying
关键词：
慢性心力衰竭（CHF）在全球范围内的患病率迅速上升，这凸显了识别早期检测CHF的生物标志物的迫切需要。翻译后修饰（ptm）与疾病进展过程中的许多关键信号事件相关，因此提供了大量的候选生物标志物。我们采用自上而下的定量蛋白质组学方法对从正常和病变组织中提取的全蛋白中的PTMs进行全面评估。我们系统地分析了36个临床人类心脏组织样本，并确定了心肌肌钙蛋白I （cTnI）的磷酸化作为CHF的候选生物标志物。在死后心脏功能正常（n=7）、早期轻度肥厚（n=5）、重度肥厚/扩张（n=4）和终末期CHF （n=6）的患者中，总磷酸化cTnI形式的相对百分比（%Ptotal）分别为56.4±3.5%、36.9±1.6%、6.1±2.4%和1.0±0.6%。在新鲜移植样本中，来自非衰竭供者（n=4）和终末期衰竭心脏（n=10）的cTnI百分比Ptotal分别为49.5±5.9%和18.8±2.9%。自上而下的电子俘获解离质谱明确地将改变的磷酸化位点定位为Ser22/23，并确定了磷酸化/去磷酸化的顺序。该研究首次将自上而下的MS-based定量蛋白质组学应用于组织生物标志物的发现，突出了PTM作为疾病生物标志物的潜力。
The rapid increase in the prevalence of chronic heart failure (CHF) worldwide underscores an urgent need to identify biomarkers for the early detection of CHF. Post-translational modifications (PTMs) are associated with many critical signaling events during disease progression and thus offer a plethora of candidate biomarkers. We have employed top-down quantitative proteomics methodology for comprehensive assessment of PTMs in whole proteins extracted from normal and diseased tissues. We have systematically analyzed thirty-six clinical human heart tissue samples and identified phosphorylation of cardiac troponin I (cTnI) as a candidate biomarker for CHF. The relative percentages of the total phosphorylated cTnI forms over the entire cTnI populations (%Ptotal) were 56.4±3.5%, 36.9±1.6%, 6.1±2.4%, and 1.0±0.6% for postmortem hearts with normal cardiac function (n=7), early-stage of mild hypertrophy (n=5), severe hypertrophy/dilation (n=4), and end-stage CHF (n=6), respectively. In fresh transplant samples, the %Ptotal of cTnI from non-failing donor (n=4), and end-stage failing hearts (n=10) were 49.5±5.9% and 18.8±2.9%, respectively. Top-down MS with electron capture dissociation unequivocally localized the altered phosphorylation sites to Ser22/23 and determined the order of phosphorylation/dephosphorylation. This study represents the first clinical application of top-down MS-based quantitative proteomics for biomarker discovery from tissues, highlighting the potential of PTM as disease biomarkers.
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影响因子：
15
作者：
Kelleher, NL;Lin, HY;McLafferty, FW
通讯作者：
McLafferty, FW
影响因子：
4.8
作者：
Gomes, AV;Liang, JS;Potter, JD
通讯作者：
Potter, JD
影响因子：
9.7
作者：
Duncker, Dirk J.;Boontje, Nicky M.;van der Velden, Jolanda
通讯作者：
van der Velden, Jolanda
DOI：
10.1016/j.jasms.2005.08.008
发表时间：
2005-12-01
影响因子：
3.2
作者：
Jebanathirajah, JA;Pittman, JL;O'Connor, PB
通讯作者：
O'Connor, PB
影响因子：
7.8
作者：
An, Hyun Joo;Kronewitter, Scott R.;de Leoz, Maria Lorna A.;Lebrilla, Carlito B.
通讯作者：
Lebrilla, Carlito B.