Proteomic Profiling for Serum Biomarkers in Mice Exposed to Ionizing Radiation

Abstract

In response to large-scale radiological incidents, rapid, accurate, and early triage biodosimeters are urgently required. In this study, we investigated candidate radiation-responsive biomarkers using proteomics approaches in mouse models. A total of 452 dysregulated proteins were identified in the serum samples of mice exposed to 0, 2, 5.5, 7, and 8 Gy at 6, 24, and 72 hours postirradiation. Ninety-eight proteins, including 46 at 6 hours, 36 at 24 hours, and 36 at 72 hours, were identified as radiation-responsive proteins (RRPs). Gene Ontology analysis showed the RRPs were involved in proteolysis, extracellular space, hydrolase activity, and carbohydrate binding. Kyoto Encyclopedia of Genes and Genome enrichment showed the RRPs were regulated in “the pentose phosphate pathway,” “the proteasome,” and “AGE-RAGE signaling in diabetic complications.” There were 3 proteins changed and overlapped at all the 3 time points, 8 proteins changed at 6 and 24 hours, 4 proteins changed at 24 and 72hours, and 2 proteins changed at both 6 and 72 hours. Of these proteins, ORM2, HP, SAA1, SAA2, MBL2, COL1A1, and APCS were identified as candidate biomarkers for biodosimeter-based diagnosis through Pearson correlation analysis.

Impact of spaceflight stressors on behavior and cognition: A molecular, neurochemical, and neurobiological perspective

“…Larger scale proteomic profiling of mice exposed to higher doses of (2-8 Gy) of gamma rays revealed several radioresponsive protein changes, many involved with metabolism, proteolysis and post-translational sugar modifications, but the early times of analyses (≤ 72h) make attributing such changes to CNS function difficult (Huang et al, 2019). Serum microRNAs (miRNA) represent another class of biomarkers that can be isolated from the blood and from circulating EV.…”

Proteomics of Non-human Primate Plasma after Partial-body Radiation with Minimal Bone Marrow Sparing

“…Comparative proteomic analyses can have additional utility toward identifying novel radiation biomarkers. Previous mass spectrometry-based untargeted proteomic profiling after radiation has been conducted in plasma or serum of mouse (Huang et al 2019a), rat (Magic et al 1995;Sun et al 2020), NHP (Rithidech et al 2009;Byrum et al 2017), and patients undergoing radiotherapy (Menard et al 2006;Widlak et al 2015;Ouerhani et al 2019). Targeted proteomic profiling of specific proteins has also been assayed in mice (Liu et al 2019).…”

Cross-platform validation of a mouse blood gene signature for quantitative reconstruction of radiation dose

“…Among these genes Phlda3 is a well-known radiation response gene in both normal human and cancer cells 44 – 46 and a known target of p53 47 . Lrg1 protein in blood has been detected as an early survival biomarker after radiotherapy for squamous cell carcinoma 48 – 50 and as a serum biomarker for radiation exposure 51 . Cd19 is a commonly used biomarker for detection of B cell development and diagnosis of leukemia 52 .…”