A Novel Redox Regulator, MnTnBuOE-2-PyP⁵⁺, Enhances Normal Hematopoietic Stem/Progenitor Cell Function

Authors

Yanming Zhao, University of KentuckyFollow
Dustin W. Carroll, University of KentuckyFollow
Y. You, University of Texas
Luksana Chaiswing, University of KentuckyFollow
R. Wen, Women and Children's Healthcare, China
I. Batinic-Haberle, Duke University
Subbarao Bondada, University of KentuckyFollow
Ying Liang, University of KentuckyFollow
Daret K. St Clair, University of KentuckyFollow

Abstract

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.

Document Type

Article

Publication Date

2-10-2017

Notes/Citation Information

Published in Redox Biology, v. 12, p. 129-138.

© 2017 The Authors. Published by Elsevier B.V.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.redox.2017.02.005

Funding Information

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].

Related Content

Supplementary data associated with this article can be found in the online version at doi:10.1016/j.redox.2017.02.005.

Repository Citation

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.
https://uknowledge.uky.edu/toxicology_facpub/66