Department of Stress Response Science, Center for Advanced Medical Research, Graduate School of Medicine, Hirosaki University, 5 Zaifu-Cho, Hirosaki, Aomori, 036-8562, Japan.
Department of Radiation Science, Graduate School of Health Sciences, Hirosaki University, 66-1 Hon-Cho, Hirosaki, Aomori, 036-8564, Japan.
Sci Rep. 2023 May 31;13(1):8802. doi: 10.1038/s41598-023-35924-9.
High doses of ionizing radiation (IR) exposure can lead to the development of severe acute radiation syndrome with bone marrow failure. Defining risk factors that predict adverse events is a critical mission to guide patient selection for personalized treatment protocols. Since non-hematopoietic stem cells act as feeder cells in the niche and their secreted lipids may regulate hematopoietic stem cells, we focused on non-hematopoietic stem cells and aimed to discover biomarkers that can assess radiation exposure from their secreted lipids. Bone marrow stromal cells (BMSCs) and osteoblast differentiation-inducing cells (ODICs) isolated from mouse femurs were exposed to lethal doses of IR and the proteomic differences between BMSC and ODIC cell layers were compared. We observed an increased Nrf2-mediated oxidative stress response and IL6 expression in ODICs and decreased expression of mitochondrial proteins in BMSCs. To elucidate secreted factors, lipidomics of the cultures were profiled; the relevant lipids distinguishing IR-exposed and control groups of BMSC were acyl-acyl phosphatidylcholine (PC aa C34:1 and PC aa C34:4), lysophosphatidylcholine (lyso-PC a C18:0 and lyso PC a C17:0) and sphingomyelin (SM C20:2). These analyses suggest that certain lipids are candidate markers for the toxic effects of IR.
高剂量电离辐射（IR）暴露可导致骨髓衰竭的严重急性辐射综合征。确定预测不良事件的风险因素是指导患者选择个性化治疗方案的关键任务。由于非造血干细胞在龛中充当滋养细胞，并且它们分泌的脂质可能调节造血干细胞，因此我们专注于非造血干细胞，并旨在发现可从其分泌的脂质评估辐射暴露的生物标志物。从小鼠股骨中分离出骨髓基质细胞（BMSC）和成骨细胞诱导分化细胞（ODIC），并用致死剂量的 IR 暴露，比较 BMSC 和 ODIC 细胞层之间的蛋白质组差异。我们观察到 ODIC 中 Nrf2 介导的氧化应激反应和 IL6 表达增加，而 BMSC 中线粒体蛋白表达减少。为了阐明分泌因子，对培养物进行了脂质组学分析；区分 BMSC 中 IR 暴露组和对照组的相关脂质为酰基酰基磷脂酰胆碱（PC aa C34:1 和 PC aa C34:4）、溶血磷脂酰胆碱（lyso-PC a C18:0 和 lyso PC a C17:0）和神经鞘磷脂（SM C20:2）。这些分析表明，某些脂质是 IR 毒性作用的候选标志物。
