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: Xiao Chai, Deguan Li, Xiaoli Cao, Yuchen Zhang, Juan Mu, Wenyi Lu, Xia Xiao, Chengcheng Li, Juanxia Meng, Jie Chen, Qing Li, Jishi Wang, Aimin Meng, Mingfeng Zhao
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 10181 (May 13 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 25970748 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Reactive Oxygen Species
• NADPH Oxidase 4
• NADPH Oxidases
• Nox4 protein, mouse
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Bone Marrow (metabolism, pathology)
• Bone Marrow Cells (metabolism, pathology)
• Bone Marrow Transplantation
• Colony-Forming Units Assay
• Disease Models, Animal
• Graft Survival
• Hematopoiesis
• Hematopoiesis, Extramedullary
• Hematopoietic Stem Cells (metabolism, pathology)
• Iron Overload (metabolism, pathology)
• Male
• Mice
• NADPH Oxidase 4
• NADPH Oxidases (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction
• p38 Mitogen-Activated Protein Kinases (metabolism)