Temporal Stability of the Urinary Proteome after Kidney Transplant: More Sensitive than Protein Composition?
Temporal Stability of the Urinary Proteome after Kidney Transplant: More Sensitive than Protein Composition?
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DOI：
10.1021/pr800646j
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发表时间：
2009-01-01
影响因子：
4.4
通讯作者：
Ibrahim, Hassan N.
中科院分区：
文献类型：
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作者：
Akkina, Sanjeev K.;Zhang, Yan;Ibrahim, Hassan N.
在4组个体中检查了时间尿蛋白质组，以确定具有明显良好肾脏健康的不同个体的时间稳定性。这些组包括（1）0时、1个月和6个月的健康志愿者，（2）手术前后的肾供体，（3）手术后立即的受体，以及（4）移植后1个月至4年的成功肾移植受体。通过尿液的反相提取，随后通过MALDI-TOF谱和iTRAQ分析检测蛋白质。仅在移植受试者中发现的MALDI-TOF谱的不寻常组分发生在m/z = 3370、3441和3385（人中性粒细胞防御素）、4303、10350和11732（β-2微球蛋白，B2 M）。m/z = 4303和11732处的峰在手术后的肾供体中也相当强烈。在移植受者中，m/z = 4303和10350处的峰与较高的血清肌酐相关。iTRAQ检测到的几种其他蛋白质以与B2 M密切相关的方式上调。总体而言，尽管不同移植受体的蛋白质组成之间存在很大差异，但通过MALDI-TOF或iTRAQ分析检测到每个个体的稳定性显著。这些结果表明，在一定限度内，谱组分的稳定性可能与蛋白质含量对肾脏健康的定义一样重要。肾移植受者尿蛋白的纵向研究可能表明不稳定性是不良肾脏健康的敏感生物标志物。
The temporal urinary proteome was examined in 4 groups of individuals in order to determine the temporal stability of diverse individuals with apparently good kidney health. The groups consisted of (1) healthy volunteers at zero time, 1 and 6 months, (2) kidney donors before and after surgery, (3) recipients immediately after surgery, and (4) successful kidney transplant recipients from 1 month to 4 years after transplant. Proteins were detected by reverse phase extraction of urine followed by MALDI-TOF profile and by iTRAQ analysis. Unusual components of the MALDI-TOF profiles found only in transplant subjects occurred at m/z = 3370, 3441 and 3385 (human neutrophil defensins), 4303, 10350, and 11732 (beta-2 microglobulin, B2M). The peaks at m/z = 4303 and 11732 were also quite intense among kidney donors following surgery. The peaks at m/z = 4303 and 10350 in transplant recipients were associated with higher serum creatinine. Several additional proteins detected by iTRAQ were up-regulated in a manner that correlated closely with B2M. Overall, despite large differences between protein composition in different transplant recipients, there was remarkable stability for each individual as detected by either MALDI-TOF or iTRAQ analyses. These results suggested that, within limits, stability of profile components may be as important as protein content for definition of kidney health. Longitudinal study of urinary proteins from kidney recipients may demonstrate instability as a sensitive biomarker of adverse kidney health.