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Identification of potential serum biomarkers of acute paraquat poisoning in humans using an iTRAQ quantitative proteomic

机译:使用iTRAQ定量蛋白质组学鉴定人类急性百草枯中毒的潜在血清生物标志物

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Paraquat (PQ) poisoning has high mortality rates in many countries. Due to it readily being absorbed through the gastrointestinal tract and rapidly excreted in the urine, few biomarkers possess satisfactory specificity and sensitivity in diagnostic and forensic practices. To investigate serum biomarkers in patients with PQ poisoning, pooled sera was analyzed using a proteomic approach based on iTRAQ coupled LC-MS/MS. Of the 413 proteins identified with high confidence, 81 were found to be differentially expressed (1.5-fold change) in the sera of patients with PQ poisoning. The differential expression pattern of 4 of these proteins was validated by enzyme-linked immunosorbent assay (ELISA) in clinical samples. A sera sample from a PQ poisoning patient has shown relatively increased abundance of S100A8 and S100A9. The overexpression of S100A8 and S100A9 was further validated in the lung tissue of PQ-treated rat associated with lung damage. Meanwhile, we identified another two down-expressed proteins, transferrin receptor protein 1 (TfR1) and serum amyloid P-component (SAP), which may be also practicable in human clinical samples as PQ poisoning serum biomarkers. Furthermore, receiver operating characteristic curve analysis confirmed that the expression levels of S100 alarmins, TfR1 and SAP in patient serum could provide a discriminatory diagnostic test for predicting PQ poisoning in patients. Therefore, our results suggest that increased serum levels of S100 alarmins and decreased serum levels of TfR1 and SAP may constitute potential biomarkers for the prediction of PQ poisoning in humans, and might be novel therapeutic targets in PQ poisoning.
机译:在许多国家,百草枯(PQ)中毒的死亡率很高。由于它很容易通过胃肠道吸收并迅速从尿中排泄,因此很少有生物标志物在诊断和法医实践中具有令人满意的特异性和敏感性。为了研究PQ中毒患者的血清生物标志物,使用基于iTRAQ耦合LC-MS / MS的蛋白质组学方法分析了合并血清。在高可信度鉴定的413种蛋白质中,发现有81种在PQ中毒患者的血清中差异表达(变化1.5倍)。通过酶联免疫吸附测定(ELISA)在临床样品中验证了其中4种蛋白质的差异表达模式。来自PQ中毒患者的血清样本显示S100A8和S100A9的丰度相对增加。 S100A8和S100A9的过表达在经PQ处理的大鼠肺组织中与肺损伤相关的进一步证实。同时,我们鉴定了另外两种低表达的蛋白,转铁蛋白受体蛋白1(TfR1)和血清淀粉样蛋白P组分(SAP),它们在人类临床样品中作为PQ中毒血清生物标志物也可能是可行的。此外,接收器工作特性曲线分析证实,患者血清中S100警报蛋白,TfR1和SAP的表达水平可以为预测患者PQ中毒提供鉴别诊断。因此,我们的结果表明,S100警报蛋白的血清水平升高以及TfR1和SAP的血清水平降低可能构成预测人类PQ中毒的潜在生物标志物,并且可能是PQ中毒的新型治疗靶标。

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