PMID- 37258593 OWN - NLM STAT- MEDLINE DCOM- 20230602 LR - 20230609 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 13 IP - 1 DP - 2023 May 31 TI - Proteomics and secreted lipidomics of mouse-derived bone marrow cells exposed to a lethal level of ionizing radiation. PG - 8802 LID - 10.1038/s41598-023-35924-9 [doi] LID - 8802 AB - 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. CI - (c) 2023. The Author(s). FAU - Tatara, Yota AU - Tatara Y AD - Department of Stress Response Science, Center for Advanced Medical Research, Graduate School of Medicine, Hirosaki University, 5 Zaifu-Cho, Hirosaki, Aomori, 036-8562, Japan. FAU - Monzen, Satoru AU - Monzen S AD - Department of Radiation Science, Graduate School of Health Sciences, Hirosaki University, 66-1 Hon-Cho, Hirosaki, Aomori, 036-8564, Japan. monzens@hirosaki-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230531 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Lipids) SB - IM MH - Mice MH - Animals MH - *Lipidomics MH - *Proteomics MH - Bone Marrow Cells MH - Radiation, Ionizing MH - Lipids PMC - PMC10232516 COIS- The authors declare no competing interests. EDAT- 2023/06/01 01:08 MHDA- 2023/06/02 06:42 PMCR- 2023/05/31 CRDT- 2023/05/31 23:20 PHST- 2022/03/30 00:00 [received] PHST- 2023/05/25 00:00 [accepted] PHST- 2023/06/02 06:42 [medline] PHST- 2023/06/01 01:08 [pubmed] PHST- 2023/05/31 23:20 [entrez] PHST- 2023/05/31 00:00 [pmc-release] AID - 10.1038/s41598-023-35924-9 [pii] AID - 35924 [pii] AID - 10.1038/s41598-023-35924-9 [doi] PST - epublish SO - Sci Rep. 2023 May 31;13(1):8802. doi: 10.1038/s41598-023-35924-9.