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  1. Article: Labile iron, ROS, and cell death are prominently induced by haemin, but not by non-transferrin-bound iron.

    Imoto, Shion / Sawamura, Tohru / Shibuya, Yukiko / Kono, Mari / Ohbuchi, Ayako / Suzuki, Takashi / Mizokoshi, Yuji / Saigo, Katsuyasu

    Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis

    2021  Volume 61, Issue 2, Page(s) 103319

    Abstract: Background: In transfusion-related iron overload, haem-derived iron accumulation in monocytes/macrophages is the initial event. When iron loading exceeds the ferritin storage capacity, iron is released into the plasma. When iron loading exceeds ... ...

    Abstract Background: In transfusion-related iron overload, haem-derived iron accumulation in monocytes/macrophages is the initial event. When iron loading exceeds the ferritin storage capacity, iron is released into the plasma. When iron loading exceeds transferrin binding capacity, labile, non-transferrin-bound iron (NTBI) appears and causes organ injury. Haemin-induced cell death has already been investigated; however, whether NTBI induces cell death in monocytes/macrophages remains unclear.
    Material and methods: Human monocytic THP-1 cells were treated with haemin or NTBI, particularly ferric ammonium citrate (FAC) or ferrous ammonium sulfate (FAS). The intracellular labile iron pool (LIP) was measured using an iron-sensitive fluorescent probe. Ferritin expression was measured by western blotting.
    Results: LIP was elevated after haemin treatment but not after FAC or FAS treatment. Reactive oxygen species (ROS) generation and cell death induction were remarkable after haemin treatment but not after FAC or FAS treatment. Ferritin expression was not different between the FAC and haemin treatments. The combination of an iron chelator and a ferroptosis inhibitor significantly augmented the suppression of haemin cytotoxicity (p = 0.011).
    Discussion: The difference in LIP suggests the different iron traffic mechanisms for haem-derived iron and NTBI. The Combination of iron chelators and antioxidants is beneficial for iron overload therapy.
    MeSH term(s) Cell Death ; Ferritins ; Hemin/pharmacology ; Humans ; Iron/metabolism ; Iron Overload ; Reactive Oxygen Species/metabolism ; Transferrin/metabolism ; Transferrin/pharmacology
    Chemical Substances Reactive Oxygen Species ; Transferrin ; Hemin (743LRP9S7N) ; Ferritins (9007-73-2) ; Iron (E1UOL152H7)
    Language English
    Publishing date 2021-11-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2046795-3
    ISSN 1878-1683 ; 1473-0502
    ISSN (online) 1878-1683
    ISSN 1473-0502
    DOI 10.1016/j.transci.2021.103319
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: After haemin treatment intracellular non-haem iron increases prior to haem oxygenase-1 induction: A study in human monocytic cell line THP-1.

    Imoto, Shion / Shibuya, Yukiko / Kono, Mari / Ohbuchi, Ayako / Sawamura, Tohru / Suzuki, Takashi / Mizokoshi, Yuji / Sawada, Hirohide / Saigo, Katsuyasu

    Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis

    2019  Volume 58, Issue 6, Page(s) 102662

    Abstract: Background: Iron overload is a major health concern for transfusion-dependent patients. Repeated transfusions result in the loading of large amounts of haem-derived iron on macrophages, in turn, inducing cell death. We previously demonstrated that ... ...

    Abstract Background: Iron overload is a major health concern for transfusion-dependent patients. Repeated transfusions result in the loading of large amounts of haem-derived iron on macrophages, in turn, inducing cell death. We previously demonstrated that haemin-induced cell death in human monocytic THP-1 cells is consistent with ferroptosis, an iron-dependent cell death regulation mechanism. However, direct measurement of iron after haemin treatment has not yet been conducted. In this study, we measured intracellular non-haem iron concentration and haem oxygenase levels after haemin treatment.
    Material and methods: Human monocytic THP-1 cells were treated with haemin, and the cell lysate was prepared. Non-haem iron concentration of the cell lysate was measured using the Nitroso-PSAP method. Expression of haem oxygenase-1 (HO-1) and haem oxygenase-2 (HO-2) was quantified by western blotting.
    Results: We measured intracellular non-haem iron and the expression of haem oxygenases post-haemin treatment. Concentration of non-haem iron post-haemin treatment increased dependently with time and dose. HO-1 expression was detected 4 h after haemin treatment, whereas HO-2 expression was constitutive.
    Discussion: Increase in non-haem iron prior to induction of HO-1 expression suggests the involvement of HO-2 in haem-induced cytotoxicity. (184 words).
    MeSH term(s) Cell Death/drug effects ; Enzyme Induction/drug effects ; Heme Oxygenase (Decyclizing)/metabolism ; Heme Oxygenase-1/biosynthesis ; Hemin/pharmacology ; Humans ; Intracellular Space/metabolism ; Iron/metabolism ; Monocytes/drug effects ; Monocytes/enzymology ; Reactive Oxygen Species/metabolism ; THP-1 Cells ; Time Factors
    Chemical Substances Reactive Oxygen Species ; Hemin (743LRP9S7N) ; Iron (E1UOL152H7) ; Heme Oxygenase (Decyclizing) (EC 1.14.14.18) ; Heme Oxygenase-1 (EC 1.14.14.18) ; heme oxygenase-2 (EC 1.14.14.18)
    Language English
    Publishing date 2019-11-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2046795-3
    ISSN 1878-1683 ; 1473-0502
    ISSN (online) 1878-1683
    ISSN 1473-0502
    DOI 10.1016/j.transci.2019.10.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Haemin-induced cell death in human monocytic cells is consistent with ferroptosis.

    Imoto, Shion / Kono, Mari / Suzuki, Takashi / Shibuya, Yukiko / Sawamura, Tohru / Mizokoshi, Yuji / Sawada, Hirohide / Ohbuchi, Ayako / Saigo, Katsuyasu

    Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis

    2018  Volume 57, Issue 4, Page(s) 524–531

    Abstract: Background: Iron overload is a major issue for transfusion-dependent patients. Repeated transfusions result in the loading of large amounts of haem-derived iron on macrophages, and the haemin in turn induces cell death and the generation of reactive ... ...

    Abstract Background: Iron overload is a major issue for transfusion-dependent patients. Repeated transfusions result in the loading of large amounts of haem-derived iron on macrophages, and the haemin in turn induces cell death and the generation of reactive oxygen species (ROS) in both murine macrophages and human monocytic THP-1 cells. This haemin-induced cell death process has been shown to be iron-dependent. Thus, we hypothesized that haemin-induced THP-1 cell death is a result of ferroptosis, an iron-dependent mechanism of cell death regulation.
    Material and methods: Human monocytic THP-1 cells were treated with haemin, and haemin-induced cell death and ROS generation were assessed using flow cytometry.
    Results: Haemin-induced THP-1 cell death showed a necrosis pattern, and treatment with iron chelators suppressed both haemin-induced cell death and ROS generation. Treatment with ferrostatin-1, a ferroptosis inhibitor, suppressed haemin-induced cell death without affecting ROS generation, whereas erastin, a ferroptosis inducer, enhanced both haemin-induced cell death and ROS generation.
    Discussion: Our findings support haemin-induced cell death as an example of ferroptosis. Therefore, ferroptosis inhibitors may be useful for the treatment or prevention of transfusion iron overload.
    MeSH term(s) Cell Death/drug effects ; Cyclohexylamines/pharmacology ; Hemin/pharmacology ; Humans ; Iron Chelating Agents/pharmacology ; Iron Chelating Agents/therapeutic use ; Macrophages/cytology ; Macrophages/drug effects ; Macrophages/metabolism ; Monocytes/cytology ; Monocytes/drug effects ; Monocytes/metabolism ; Phenylenediamines/pharmacology ; Reactive Oxygen Species/blood ; Reactive Oxygen Species/metabolism ; THP-1 Cells
    Chemical Substances Cyclohexylamines ; Iron Chelating Agents ; Phenylenediamines ; Reactive Oxygen Species ; ferrostatin-1 ; Hemin (743LRP9S7N)
    Language English
    Publishing date 2018-05-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 2046795-3
    ISSN 1878-1683 ; 1473-0502
    ISSN (online) 1878-1683
    ISSN 1473-0502
    DOI 10.1016/j.transci.2018.05.028
    Database MEDical Literature Analysis and Retrieval System OnLINE

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