Journal
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
Volume 96, Issue 5, Pages 584-595Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/09553002.2020.1708993
Keywords
Hematopoietic acute radiation sickness; ferroptosis; iron accumulation; iron metabolism
Funding
- National Natural Science Foundation of China [11575086, 11705089, 11775115, 81571805]
- Postdoctoral Science Foundation of China [2017M611660]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
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Purpose: To study whether radiation-induced bleeding in the bone marrow induced iron accumulation, and subsequently caused ferroptosis in granulocyte-macrophage hematopoietic progenitor cells. Materials and methods: Male mice were subjected to different doses (0, 4, 8, or 10 Gy) of gamma radiation from a Cs-137 source. The changes in iron metabolism or ferroptosis-related parameters of irradiated bone marrow were accessed with biochemical, histopathological, and antibody methods. Hematocytes were detected with a hematology analyzer. The counts of granulocyte-macrophage hematopoietic progenitor cells were measured with the granulocyte-macrophage colony-forming unit. Results: Iron accumulation occurred in the bone marrow, which caused by radiation-induced hemorrhage. The iron accumulation triggered an iron regulatory protein-ferroportin 1 axis to increase serum iron levels. Using LDN193189, radiation-induced iron accumulation was demonstrated to decrease white blood cell counts at least partly through a decrease in the counts of granulocyte-macrophage hematopoietic progenitor cells. The reduction in the counts of granulocyte-macrophage hematopoietic progenitor cells was subsequently demonstrated to attribute to ferroptosis with the use of ferroptosis inhibitors and through the detection of ferroptosis related-parameters. The survival rate of irradiated mice was improved using Ferrostatin-1 or LDN193189. Conclusions: These findings suggest that radiation-induced hemorrhage in the bone marrow causes ferroptosis in granulocyte-macrophage hematopoietic progenitor cells, and anti-ferroptosis has the potential to be a radioprotective strategy to ameliorate radiation-induced hematopoietic injury. [GRAPHICS] .
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