Identification of the differentially expressed protein biomarkers in rat blood plasma in response to gamma irradiation

Abstract

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.

Keywords:

• LC-MS/MS
• TMT
• radiation exposure
• mass spectrometry
• proteomics

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing the paper.

Additional information

Funding

This work was supported by the grants from National Natural Science Foundation of China [grant nos. 81573081 and 81803162].

Notes on contributors

Jia-Li Sun

Jia-Li Sun, MMS. Her research field is biological effects of radiation.

Shuang Li

Shuang Li, MD, is a Research Associate in the Department of Radiobiology, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention. Her research fields are biological effects of radiation and radiation biodosimetry.

Xue Lu

Xue Lu, BA, is an Associate Senior Technician in the Department of Radiobiology, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention.

Jiang-Bin Feng

Jiang-Bin Feng, BA, is an Associate Senior Technician in the Department of Radiobiology, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention.

Tian-Jing Cai

Tian-Jing Cai, MPH, is a Research Associate in the Department of Radiobiology, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention.

Mei Tian

Mei Tian, PhD, is a Chief of the Department of Radiobiology, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention.

Qing-Jie Liu

Qing-Jie Liu, MD/PhD, is a professor of Radiobiology, Deputy Director General, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention. His research fields are biological effects of radiation and radiation biodosimetry.