The signaling of reactive oxygen species (ROS) is essential for the maintenance of normal cellular function. However, whether and how ROS regulate stem cells are unclear. Here, we demonstrate that, in transgenic mice expressing the human manganese superoxide dismutase (MnSOD) gene, a scavenger of ROS in mitochondria, the number and function of mouse hematopoietic stem/progenitor cells (HSPC) under physiological conditions are enhanced. Importantly, giving MnTnBuOE-2-PyP5+(MnP), a redox- active MnSOD mimetic, to mouse primary bone marrow cells or to C57B/L6 mice significantly enhances the number of HSPCs. Mechanistically, MnP reduces superoxide to hydrogen peroxide, which activates intracellular Nrf2 signaling leading to the induction of antioxidant enzymes, including MnSOD and catalase, and mitochondrial uncoupling protein 3. The results reveal a novel role of ROS signaling in regulating stem cell function, and suggest a possible beneficial effect of MnP in treating pathological bone marrow cell loss and in increasing stem cell population for bone marrow transplantation.
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The work is supported by the Edward P. Evans Foundation, NCI Cancer Center Support Grant [P30 CA177558] and National Institute of Health training Grant [T32 ES007266].
Supplementary data associated with this article can be found in the online version at doi:10.1016/j.redox.2017.02.005.
Zhao, Yanming; Carroll, Dustin W.; You, Y.; Chaiswing, Luksana; Wen, R.; Batinic-Haberle, I.; Bondada, Subbarao; Liang, Ying; and St Clair, Daret K., "A Novel Redox Regulator, MnTnBuOE-2-PyP5+, Enhances Normal Hematopoietic Stem/Progenitor Cell Function" (2017). Toxicology and Cancer Biology Faculty Publications. 66.