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Identification of the differentially expressed protein biomarkers in rat blood plasma in response to gamma irradiation.
International Journal of Radiation Biology ( IF 2.1 ) Pub Date : 2020-03-19 , DOI: 10.1080/09553002.2020.1739775
Jia-Li Sun 1, 2 , Shuang Li 1 , Xue Lu 1 , Jiang-Bin Feng 1 , Tian-Jing Cai 1 , Mei Tian 1 , Qing-Jie Liu 1
Affiliation  

Purpose: Simple, rapid and high-throughput dose assessment is critical for clinical diagnosis, treatment and emergency intervention in a large-scale radiological accident. The goal of this study is to screen and identify new ionizing radiation-responsive protein biomarkers in rat plasma.

Materials and methods: Sprague-Dawley rats were exposed to single doses of 0, 1, 3, 5 Gy of Cobalt-60 γ-rays total body irradiation at a dose rate of 1 Gy/min. The tandem mass tag labeling (TMT) combined with liquid chromatography mass spectrometry (LC-MS/MS) approach was used to screen the differentially expressed proteins in rat plasma collected at 1, 3, 5 and 7 days post-irradiation. Bioinformatics analysis was conducted to explore the biological functions of these proteins. The expression levels of candidate radiation-sensitive protein biomarkers were confirmed using enzyme-linked immune-sorbent assay (ELISA).

Results: A total of 503 differentially expressed proteins were identified. Most of these proteins were implicated in immune response, phagocytosis and signal transduction following ionizing radiation. Five up-regulated proteins including alpha-2-macroglobulin (A2m), chromogranin-A (CHGA), glutathione pertidase 3 (GPX3), clusterin (Clu) and ceruloplasmin (Cp) were selected for ELISA analysis. It was found that the expression levels of A2m, CHGA and GPX3 protein were increased in a dose-dependent manner at 1, 3 and 5 days after irradiation.

Conclusion: Proteomics analysis revealed radiation-induced differentially expressed proteins in rat plasma. Our results suggested that A2m, CHGA, GPX3 protein expressions alterations in rat plasma may have potential as biomarkers to evaluate radiation exposure.



中文翻译:

响应伽马射线辐照大鼠血浆中差异表达的蛋白质生物标记物的鉴定。

目的:简单,快速,高通量的剂量评估对于大规模放射事故的临床诊断,治疗和紧急干预至关重要。这项研究的目的是在大鼠血浆中筛选和鉴定新的电离辐射反应性蛋白质生物标记。

材料和方法: Sprague-Dawley大鼠以1 Gy / min的剂量率暴露于0、1、3、5 Gy的Cobalt-60γ射线全身辐射单剂量。串联质谱标签(TMT)结合液相色谱质谱法(LC-MS / MS)用于筛选辐照后1、3、5和7天收集的大鼠血浆中差异表达的蛋白质。进行了生物信息学分析以探索这些蛋白质的生物学功能。使用酶联免疫吸附测定(ELISA)确认候选放射敏感性蛋白生物标志物的表达水平。

结果:共鉴定到503种差异表达的蛋白质。这些蛋白质中的大多数与电离辐射后的免疫应答,吞噬作用和信号转导有关。ELISA分析选择了五个上调的蛋白,包括α-2-巨球蛋白(A2m),嗜铬粒蛋白A(CHGA),谷胱甘肽过氧化物酶3(GPX3),簇蛋白(Clu)和铜蓝蛋白(Cp)。发现在照射后1、3和5天,A2m,CHGA和GPX3蛋白的表达水平以剂量依赖性方式增加。

结论:蛋白质组学分析揭示了辐射诱导的大鼠血浆中差异表达的蛋白质。我们的结果表明,大鼠血浆中A2m,CHGA,GPX3蛋白表达的改变可能具有潜在的生物标志物来评估辐射暴露。

更新日期:2020-03-19
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