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Pharmacological Modulation of Redox Status in Bone Marrow

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Systems Biology of Free Radicals and Antioxidants

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Abstract

Redox regulation and thiol balance have critical roles in multiple pathways that control myeloproliferation, hematopoietic progenitor cell mobilization, and immune response. Development of redox-modulating anticancer drugs is frequently limited by dose-limiting toxicities including myelosuppression and immunosuppression. This chapter discusses the role of redox status and the equilibrium of free thiol-disulfide couples in the bone marrow niche environment and how certain classes of drugs modulate hematopoiesis and the immune response.

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Abbreviations

AP-1:

Activator protein-1

APC:

Antigen-presenting cell

BSO:

Buthionine sulfoximine

Cys:

Cysteine

CySS:

Cystine

DC:

Dendritic cell

FoxO:

Forkhead O

GGT:

Gamma-glutamyltransferase

GPx:

Glutathione peroxidase

GR:

Glutathione reductase

Grx:

Glutaredoxin

GSH:

Reduced glutathione

GSSG:

Oxidized glutathione

GST:

Glutathione S-transferase

HPCs:

Hematopoietic progenitor cells

HSC:

Hematopoietic stem cell

IR:

Ionizing radiation

JNK:

c-jun NH2-terminal kinase

MAPK:

Mitogen-activated protein kinase

NAC:

N-acetyl-cysteine

NF-κB:

Nuclear factor κB

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

Th1:

T helper cell type 1

Th2:

T helper cell type 2

Trx:

Thioredoxin

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  1. Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC, 29425-5050, USA

    Christina L. Grek & Kenneth D. Tew

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  1. Christina L. Grek
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  2. Kenneth D. Tew
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  1. Department of Pharmacology and Therapeutics, University of British Colombia, Vancouver, British Columbia, Canada

    Ismail Laher

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Grek, C.L., Tew, K.D. (2014). Pharmacological Modulation of Redox Status in Bone Marrow. In: Laher, I. (eds) Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30018-9_134

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