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. 2014:122:1-67.
doi: 10.1016/B978-0-12-420117-0.00001-3.

Reactive oxygen species in normal and tumor stem cells

Daohong Zhou  1 , Lijian Shao  2 , Douglas R Spitz  3
Affiliations

Reactive oxygen species in normal and tumor stem cells

Daohong Zhou et al. Adv Cancer Res. 2014.

Abstract

Reactive oxygen species (ROS) play an important role in determining the fate of normal stem cells. Low levels of ROS are required for stem cells to maintain quiescence and self-renewal. Increases in ROS production cause stem cell proliferation/differentiation, senescence, and apoptosis in a dose-dependent manner, leading to their exhaustion. Therefore, the production of ROS in stem cells is tightly regulated to ensure that they have the ability to maintain tissue homeostasis and repair damaged tissues for the life span of an organism. In this chapter, we discuss how the production of ROS in normal stem cells is regulated by various intrinsic and extrinsic factors and how the fate of these cells is altered by the dysregulation of ROS production under various pathological conditions. In addition, the implications of the aberrant production of ROS by tumor stem cells for tumor progression and treatment are also discussed.

Keywords: Adult stem cells; Apoptosis; Differentiation; Embryonic stem cells; Hematopoietic stem cells; Hypoxia; Ionizing radiation; Reactive oxygen species; Senescence; Tumor stem cells.

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Figures

Figure 1.1
Figure 1.1
Mitochondrial electron transport chains can form superoxide and hydrogen peroxide that can act as signaling molecules transducing redox signals from metabolic processes to the nucleus. OMM, outer mitochondrial membrane; IMM, inner mitochondrial membrane; VDAC, voltage-dependent anionic channel; Ref-1, redox factor 1; FMN, flavin mononucleotide; mPTP, mitochondrial permeability transition pore; MnSOD, manganese superoxide dismutase; CuZnSOD, copper/zinc superoxide dismutase; Cyt-C, cytochrome C.
Figure 1.2
Figure 1.2
Theoretical model outlining redox couples and antioxidant pathways that coordinately regulate the flow of electrons from metabolism to redox-sensitive signaling and gene expression pathways contributing to the maintenance of the non-equilibrium steady state necessary for normal cellular functions during growth and development. TCA, tricarboxylic acid cycle; PPC, pentose phosphate cycle; GR, glutathione reductase; TR, thioredoxin reductase; GSH/GSSG, glutathione/glutathione disulfide; TrxS2H2/TrxSS, thioredoxin reduced and oxidized; GPX, glutathione peroxidase; Prx, peroxiredoxin; sites I–IV, electron transport chain complexes I–IV; Ref-1, redox factor 1.
Figure 1.3
Figure 1.3
Theoretical model describing the interrelationship between metabolic and genetic processes necessary for life and death of mammalian organisms. ROS, reactive oxygen species; RNS, reactive nitrogen species.
Figure 1.4
Figure 1.4
Life cycle through stem cells. ICM, inner cell mass; ESCs, embryonic stem cells; iPSCs, inducible pluripotent stem cells.
Figure 1.5
Figure 1.5
A hierarchical model of the hematopoietic system. LT-HSC, long-term hematopoietic stem cell; ST-HSC, short-term HSC; HSC, hematopoietic stem cell; MPP, multipotent progenitor; LMPP/MLP, lymphoid-primed multipotent progenitor/multilymphoid progenitor; CMP, common myeloid progenitor; CLP, common lymphoid progenitor; MEP, megakaryocyte/erythroid progenitor; GMP, granulocyte/monocyte progenitor.
Figure 1.6
Figure 1.6
Theoretical model illustrating the regulation of ROS production in HSCs and the effects of ROS on HSCs. HSCs, hematopoietic stem cells; IR, ionizing radiation; NOXs, NADPH oxidases; mTORC1, mammalian target of rapamycin complex 1; HIF-1, hypoxia-inducible factor-1; OXPHOS, oxidative phosphorylation; SOD, superoxide dismutase; ROS, reactive oxygen species; FOXOs, forkhead box O transcription factors; DSBs, DNA double-strand breaks; ATM, ataxia-telangiectasia mutated.
Figure 1.7
Figure 1.7
A diagram illustrating the relationship of cell metabolism, ROS production, and HSC self-renewal under increasing concentrations of oxygen and after exposure to IR and stress. HSC, hematopoietic stem cell; IR, ionizing radiation; OXPHOS, oxidative phosphorylation; ROS, reactive oxygen species.
See this image and copyright information in PMC

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