Ionizing radiation induces ferroptosis in granulocyte-macrophage hematopoietic progenitor cells of murine bone marrow

Zhang, Xiaohong; Xing, Xiaolong; Liu, Huiwen; Feng, Jundong; Tian, Mengmeng; Chang, Shuquan; Liu, Peidang; Zhang, Haiqian

doi:10.1080/09553002.2020.1708993

Cited by 50 publications

(42 citation statements)

References 36 publications

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“…Excessive iron uptake also affects the immune function of mature macrophages, suppressing normal antimicrobial activity [14,60]. In both experimental animal studies and studies of patients with iron overload, iron chelation had beneficial effects on hematopoietic cell recovery [15,59], and a recent study found that iron chelation following TBI had beneficial effects for survival and hematopoietic recovery [33]. Additional studies are required to determine whether iron also accumulates in other tissues and whether iron from radiation hemolysis could be a general mechanism of tissue injury afterTBI.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies indicated that dietary iron overload can lead to iron deposition in the bone marrow [15]. A recent study of TBI also found that iron can be deposited in the bone marrow [33]. We examined bone marrow sections from mice exposed to TBI to examine the time course of radiation-induced iron in the bone marrow.…”

Section: Iron Accumulates In Macrophages Of the Bone Marrow Following Tbimentioning

confidence: 99%

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Deposition of Iron in the Bone Marrow of a Murine Model of Hematopoietic Acute Radiation Syndrome

Rittase

Muir

Slaven

et al. 2020

Experimental Hematology

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Exposure to high-dose total body irradiation (TBI) can result in hematopoietic acute radiation syndrome (H-ARS), characterized by leukopenia, anemia, and coagulopathy. Death from H-ARS occurs from hematopoietic insufficiency and opportunistic infections. Following radiation exposure, red blood cells (RBCs) undergo hemolysis from radiation-induced hemoglobin denaturation, causing the release of iron. Free iron can have multiple detrimental biological effects, including suppression of hematopoiesis. We investigated the impact of radiation-induced iron release on the bone marrow following TBI and the potential impact of the ACE inhibitor captopril, which improves survival from H-ARS. C57BL/6J mice were exposed to 7.9 Gy, 60 Co irradiation, 0.6 Gy/min (LD 70−90/30 ). RBCs and reticulocytes were significantly reduced within 7 days of TBI, with the RBC nadir at 14−21 days. Iron accumulation in the bone marrow correlated with the time course of RBC hemolysis, with an »10-fold increase in bone marrow iron at 14−21 days post-irradiation, primarily within the cytoplasm of macrophages. Iron accumulation in the bone marrow was associated with increased expression of genes for iron binding and transport proteins, including transferrin, transferrin receptor 1, ferroportin, and integrin aMb2. Expression of the gene encoding Nrf2, a transcription factor activated by oxidative stress, also increased at 21 days post-irradiation. Captopril did not alter iron accumulation in the bone marrow or expression of iron storage genes, but did suppress Nrf2 expression. Our study suggests that following TBI, iron is deposited in tissues not normally associated with iron storage, which may be a secondary mechanism of radiation-induced tissue injury. Published by Elsevier Inc. on behalf of ISEH -Society for Hematology and Stem Cells. This is an open access article under the CC BY-NC-ND license.

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Section: Discussionmentioning

confidence: 99%

Section: Iron Accumulates In Macrophages Of the Bone Marrow Following Tbimentioning

confidence: 99%

Deposition of Iron in the Bone Marrow of a Murine Model of Hematopoietic Acute Radiation Syndrome

Rittase

Muir

Slaven

et al. 2020

Experimental Hematology

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“…112 Ferroptosis also occurs in macrophages. [113][114][115] However, compared with cancer cells, macrophages exert higher resistance to ferroptosis. Erastin and deleting SLC7A11 expression were not sufficient to induce macrophage ferroptosis unless under high iron conditions.…”

Section: The Interaction Of Ferroptosis and Lipid Metabolism Modulatementioning

confidence: 99%

The interaction between ferroptosis and lipid metabolism in cancer

2020

Sig Transduct Target Ther

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285

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Ferroptosis is a new form of programmed cell death characterized by the accumulation of iron-dependent lethal lipid peroxides. Recent discoveries have focused on alterations that occur in lipid metabolism during ferroptosis and have provided intriguing insights into the interplay between ferroptosis and lipid metabolism in cancer. Their interaction regulates the initiation, development, metastasis, therapy resistance of cancer, as well as the tumor immunity, which offers several potential strategies for cancer treatment. This review is a brief overview of the features characterizing the interaction between ferroptosis and lipid metabolism, and highlights the significance of this interaction in cancer.

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“…Recently, several groups discovered that radiation can induce ferroptosis, that ferroptosis inducers can act as radiosensitizers, and that ferroptosis inhibitors can block the effects of radiation (Lei et al, 2020;Li et al, 2019aLi et al, , 2019bYe et al, 2020;Zhang et al, 2020). This provides a new approach to treat both radiosensitive and radioresistant cancers, as well as side effects of radiation on normal tissues.…”

Section: Other Inducers Of Ferroptosismentioning

confidence: 99%

The Chemistry and Biology of Ferroptosis

Stockwell

Jiang

2020

Cell Chemical Biology

246

203

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Àinhibitor (Gout et al., 2001). However, sulfasalazine has very low potency, and is metabolically unstable in vivo, making it difficult to use in animal studies; it is best used as a confirmatory tool in cell culture studies. The compounds DPI2 (Yang et al., 2014) and RSL5 (Yang and Stockwell, 2008) have similar effects as erastin, and may also be system x c À inhibitors, although this potential mechanism has not been tested directly (Figure 1; Table 1).The amino acid and neurotransmitter glutamate has also been shown to inhibit system x c À and to induce ferroptosis in some cellular contexts (Murphy et al., 1989). Glutamate has a variety

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Ionizing radiation induces ferroptosis in granulocyte-macrophage hematopoietic progenitor cells of murine bone marrow

Cited by 50 publications

References 36 publications

Deposition of Iron in the Bone Marrow of a Murine Model of Hematopoietic Acute Radiation Syndrome

Deposition of Iron in the Bone Marrow of a Murine Model of Hematopoietic Acute Radiation Syndrome

The interaction between ferroptosis and lipid metabolism in cancer

The Chemistry and Biology of Ferroptosis

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