TY - JOUR
T1 - A novel redox regulator, MnTnBuOE-2-PyP5+, enhances normal hematopoietic stem/progenitor cell function
AU - Zhao, Y.
AU - Carroll, D. W.
AU - You, Y.
AU - Chaiswing, L.
AU - Wen, R.
AU - Batinic-Haberle, I.
AU - Bondada, S.
AU - Liang, Y.
AU - St. Clair, D. K.
N1 - Publisher Copyright:
© 2017 The Authors
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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.
AB - 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.
KW - Mitochondrial
KW - MnSOD
KW - Nrf2
KW - ROS
KW - Stem
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U2 - 10.1016/j.redox.2017.02.005
DO - 10.1016/j.redox.2017.02.005
M3 - Article
C2 - 28231483
AN - SCOPUS:85013361131
SN - 2213-2317
VL - 12
SP - 129
EP - 138
JO - Redox Biology
JF - Redox Biology
ER -