The mechanisms for the radioprotective effect of beta-d-glucan on high linear-energy-transfer carbon ion irradiated mice

Abstract

S. cerevisiae-derived-beta-d-glucan (S. cerevisiae-BG) is a natural polysaccharide with various biological effects. The present study was to investigate the protective effect of S. cerevisiae-BG on the injury induced by high linear-energy-transfer (LET) carbon ion irradiation and to reveal the protective mechanisms. Female mice were orally administrated with S. cerevisiae-BG before irradiation. 30-day survival of 6 Gy irradiated-mice was monitored. The damage and recovery of hematopoietic system were evaluated after 2 Gy irradiation, cytokines in plasma were detected, transcriptomics of bone marrow mononuclear cells (BMMNCs) were detected and analyzed. The mortality results showed that S. cerevisiae-BG could prolong the survival of mice exposed to 6 Gy. The results of BMMNCs injury analysis showed that S. cerevisiae-BG could reduce the ROS level, mitigate DNA damage and apoptosis. S. cerevisiae-BG increased the plasma radioprotective cytokines level in irradiated mice. Transcriptomics analysis revealed that S. cerevisiae-BG modulated the gene expression in BMMNCs of irradiated mice, 256 genes were significantly up-regulated and 97 genes were significantly down-regulated. Gene function and Gene Ontology analysis indicated the key genes related to hematopoiesis and immunity. Pathway analysis revealed that these up-regulated genes mainly focus on PI3K-Akt pathway and down-regulated genes mainly focus on MAPK pathway. These data contribute to understanding the molecular mechanisms of the radioprotective effect of S. cerevisiae-BG.

Keywords: Carbon ion irradiation; Murine bone marrow; Radioprotective mechanism; S. cerevisiae-derived-beta-d-glucan.