A novel redox regulator, MnTnBuOE-2-PyP5+, enhances normal hematopoietic stem/progenitor cell function

Y. Zhao; D. W. Carroll; Y. You; L. Chaiswing; R. Wen; I. Batinic-Haberle; S. Bondada; Y. Liang; D. K. St. Clair

doi:10.1016/j.redox.2017.02.005

A novel redox regulator, MnTnBuOE-2-PyP⁵⁺, enhances normal hematopoietic stem/progenitor cell function

Y. Zhao, D. W. Carroll, Y. You, L. Chaiswing, R. Wen, I. Batinic-Haberle, S. Bondada, Y. Liang, D. K. St. Clair

Research output: Contribution to journal › Article › peer-review

39 Citations (SciVal)

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.

Original language	English
Pages (from-to)	129-138
Number of pages	10
Journal	Redox Biology
Volume	12
DOIs	https://doi.org/10.1016/j.redox.2017.02.005
State	Published - Aug 1 2017

Bibliographical note

Funding Information:
The work is supported by the Edward P. Evans Foundation, NCI Cancer Center Support Grant [P30 CA177558] and National Institute of Health a training Grant [T32 ES007266]. The authors thank Dr. Mihail Mitov, Operations Manager of the University of Kentucky Redox Metabolism Shared Resource Facility, (RM SRF) for technical advice and support. We also thank the University of Kentucky Flow Cytometry Shared Facility and Teresa Noel and Chontida Yarana for their technical help.

Publisher Copyright:
© 2017 The Authors

Keywords

Mitochondrial
MnSOD
Nrf2
ROS
ROS
Stem

ASJC Scopus subject areas

Organic Chemistry
Clinical Biochemistry

Access to Document

10.1016/j.redox.2017.02.005

Cite this

@article{4c1fdb3460974a738f941c2f783d154a,

title = "A novel redox regulator, MnTnBuOE-2-PyP5+, enhances normal hematopoietic stem/progenitor cell function",

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.",

keywords = "Mitochondrial, MnSOD, Nrf2, ROS, ROS, Stem",

author = "Y. Zhao and Carroll, {D. W.} and Y. You and L. Chaiswing and R. Wen and I. Batinic-Haberle and S. Bondada and Y. Liang and {St. Clair}, {D. K.}",

note = "Funding Information: The work is supported by the Edward P. Evans Foundation, NCI Cancer Center Support Grant [P30 CA177558] and National Institute of Health a training Grant [T32 ES007266]. The authors thank Dr. Mihail Mitov, Operations Manager of the University of Kentucky Redox Metabolism Shared Resource Facility, (RM SRF) for technical advice and support. We also thank the University of Kentucky Flow Cytometry Shared Facility and Teresa Noel and Chontida Yarana for their technical help. Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2017",

month = aug,

day = "1",

doi = "10.1016/j.redox.2017.02.005",

language = "English",

volume = "12",

pages = "129--138",

}

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 - Funding Information: The work is supported by the Edward P. Evans Foundation, NCI Cancer Center Support Grant [P30 CA177558] and National Institute of Health a training Grant [T32 ES007266]. The authors thank Dr. Mihail Mitov, Operations Manager of the University of Kentucky Redox Metabolism Shared Resource Facility, (RM SRF) for technical advice and support. We also thank the University of Kentucky Flow Cytometry Shared Facility and Teresa Noel and Chontida Yarana for their technical help. 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

UR - http://www.scopus.com/inward/record.url?scp=85013361131&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85013361131&partnerID=8YFLogxK

U2 - 10.1016/j.redox.2017.02.005

DO - 10.1016/j.redox.2017.02.005

M3 - Article

C2 - 28231483

AN - SCOPUS:85013361131

VL - 12

SP - 129

EP - 138

ER -