Tandem Mass Tag-Based Quantitative Proteomic Analysis Reveals Pathways Involved in Brain Injury Induced by Chest Exposure to Shock Waves.

Changci Tong,Yunen Liu,Ying Liu,Peifang Cong,Xiuyun Shi,Shun Mao,Mingxiao Hou,Lin Shi,Yan Zhao

doi:10.3389/fnmol.2021.688050

Abstract

Recurrent chest blast exposure can lead to brain inflammation, oxidative stress, and mental disorders in soldiers. However, the mechanism that underlies brain injury caused indirectly by chest blasts remains unclear. It is urgent to find additional reliable biomarkers to reveal the intimate details of the pathogenesis of this phenomenon. We used the term tandem mass tag (TMT) labeling combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS) to screen for differentially expressed proteins in rat brain at different time points after a chest blast. Data are available via ProteomeXchange with the identifier PXD025204. Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), the Database for Annotation, Visualization and Integrated Discovery (DAVID), and Cytoscape analyses were used to analyze the proteomic profiles of blast-exposed rats. In addition, we performed Western blotting to verify protein levels. We identified 6,931 proteins, of which 255 were differentially expressed and 43, 84, 52, 97, and 49 were identified in brain tissues at 12, 24, 48, and 72 h and 1 week after chest blast exposure, respectively. In this study, the GO, KEGG, Clusters of Orthologous Groups of proteins, and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analyses indicated that brain damage caused by chest blast exposure involved many important biological processes and signaling pathways, such as inflammation, cell adhesion, phagocytosis, neuronal and synaptic damage, oxidative stress, and apoptosis. Furthermore, Western blotting confirmed that these differentially expressed proteins and affected signaling pathways were associated with brain damage caused by chest blast exposure. This study identifies potential protein biomarkers of brain damage caused indirectly by chest blast and new targets for the treatment of this condition.

Highlights

In recent years, the increased numbers of local conflicts and terrorist attacks throughout the world have increased the incidence of explosion events year by year
Chest blast exposure increased the expression of proinflammatory cytokines, IL-4 and NF-κ B; decreased the expression of anti-oxidative stress, HO-1 and SOD-1; increased the expression of inositol-requiring enzyme α (IREα) and Bcl-2 agonist of cell death (Bad); and decreased the expression of Bcl-xL compared with the control group
We have previously shown that chest blast exposure can lead to changes in perivascular inflammatory cells, oxidative stress, apoptosis, and behavioral changes in mice (Cong et al, 2019b)

Summary

Introduction

The increased numbers of local conflicts and terrorist attacks throughout the world have increased the incidence of explosion events year by year. These explosion events may cause traumatic brain injury, which is a leading cause of morbidity and mortality worldwide. It is followed by various biochemical changes (Surgucheva et al, 2014). In China, explosions involving dangerous chemical goods, such as the Tianjin Port “8.12” explosion (Dong et al, 2021) and the Taiwan “6.27” dust explosion (Chen L.-R. et al, 2018), caused major economic losses and social impacts and seriously affected the lives of people. Several research groups have provided evidence that explosive energy triggers acute glial inflammation, leading to chronic neurobehavioral and neuropathological outcomes (Arun et al, 2020; Dickstein et al, 2020; Logsdon et al, 2020)

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