1. Academic Validation
  2. Haemin-induced cell death in human monocytic cells is consistent with ferroptosis

Haemin-induced cell death in human monocytic cells is consistent with ferroptosis

  • Transfus Apher Sci. 2018 Aug;57(4):524-531. doi: 10.1016/j.transci.2018.05.028.
Shion Imoto 1 Mari Kono 2 Takashi Suzuki 3 Yukiko Shibuya 3 Tohru Sawamura 3 Yuji Mizokoshi 3 Hirohide Sawada 3 Ayako Ohbuchi 4 Katsuyasu Saigo 4
Affiliations

Affiliations

  • 1 Department of Health Science, Kobe Tokiwa University, 2-6-2 Ootani-cho, Nagata-ku, Kobe 653-0838, Japan. Electronic address: [email protected].
  • 2 Scientific Research, Scientific Affairs, Sysmex Corporation, 1-3-2 Murotani, Nishi-ku, Kobe 651-2241, Japan.
  • 3 Department of Health Science, Kobe Tokiwa University, 2-6-2 Ootani-cho, Nagata-ku, Kobe 653-0838, Japan.
  • 4 Faculty of Pharmacological Sciences, Himeji Dokkyo University, 7, Kami-ohno, Himeji, Hyogo 670-8524, Japan.
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.

Keywords

Ferroptosis; Haemin; Iron chelators; Macrophages; Transfusion iron overload.

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