title: ROS-mediated iron overload injures the hematopoiesis of bone marrow by damaging hematopoietic stem/progenitor cells in mice.
abstract: Iron overload, caused by hereditary hemochromatosis or repeated blood transfusions in some diseases, such as beta thalassemia, bone marrow failure and myelodysplastic syndrome, can significantly induce injured bone marrow (BM) function as well as parenchyma organ dysfunctions. However, the effect of iron overload and its mechanism remain elusive. In this study, we investigated the effects of iron overload on the hematopoietic stem and progenitor cells (HSPCs) from a mouse model. Our results showed that iron overload markedly decreased the ratio and clonogenic function of murine HSPCs by the elevation of reactive oxygen species (ROS). This finding is supported by the results of NAC or DFX treatment, which reduced ROS level by inhibiting NOX4 and p38MAPK and improved the long-term and multi-lineage engrafment of iron overload HSCs after transplantation. Therefore, all of these data demonstrate that iron overload injures the hematopoiesis of BM by enhancing ROS through NOX4 and p38MAPK. This will be helpful for the treatment of iron overload in patients with hematopoietic dysfunction.
authors.affiliation: 1] Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, China [2] Department of Hematology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chai
authors.affiliation: Tianjin Key Lab of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China.
authors.forename: Deguan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Mu
authors.affiliation: Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Tianjin Key Lab of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Juanxia
authors.initials: J
authors.lastname: Meng
authors.affiliation: Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Hematology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.
authors.forename: Jishi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Tianjin Key Lab of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Meng
authors.affiliation: Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology*; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D016026:Bone Marrow Transplantation; D003114:Colony-Forming Units Assay; D004195:Disease Models, Animal; D006085:Graft Survival; D006410:Hematopoiesis; D006411:Hematopoiesis, Extramedullary; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D019190:Iron Overload / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases