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International Journal of Hematology

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01.07.2011 | Progress in Hematology

Reactive oxygen species and hematopoietic stem cell senescence

verfasst von: Lijian Shao, Hongliang Li, Senthil K. Pazhanisamy, Aimin Meng, Yong Wang, Daohong Zhou

Erschienen in: International Journal of Hematology | Ausgabe 1/2011

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Abstract

Hematopoietic stem cells (HSCs) are responsible for sustaining hematopoietic homeostasis and regeneration after injury for the entire lifespan of an organism through self-renewal, proliferation, differentiation, and mobilization. Their functions can be affected by reactive oxygen species (ROS) that are produced endogenously through cellular metabolism or after exposure to exogenous stress. At physiological levels, ROS function as signal molecules which can regulate a variety of cellular functions, including HSC proliferation, differentiation, and mobilization. However, an abnormal increase in ROS production occurs under various pathological conditions, which can inhibit HSC self-renewal and induce HSC senescence, resulting in premature exhaustion of HSCs and hematopoietic dysfunction. This review aims to provide a summary of a number of recent findings regarding the cellular sources of ROS in HSCs and the mechanisms of action whereby ROS induce HSC senescence. In particular, we highlight the roles of the p38 mitogen-activated protein kinase (p38)-p16^Ink4a (p16) pathway in mediating ROS-induced HSC senescence.

Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11:298–300.PubMed

Perez VI, Bokov A, Van Remmen H, Mele J, Ran Q, Ikeno Y, Richardson A. Is the oxidative stress theory of aging dead? Biochim Biophys Acta. 2009;1790:1005–14.PubMed

Salmon AB, Richardson A, Perez VI. Update on the oxidative stress theory of aging: does oxidative stress play a role in aging or healthy aging? Free Radic Biol Med. 2010;48:642–55.PubMedCrossRef

Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K, Ohmura M, Naka K, Hosokawa K, Ikeda Y, Suda T. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med. 2006;12:446–51.PubMedCrossRef

Ito K, Takubo K, Arai F, Satoh H, Matsuoka S, Ohmura M, Naka K, Azuma M, Miyamoto K, Hosokawa K, Ikeda Y, Mak TW, Suda T, Hirao A. Regulation of reactive oxygen species by Atm is essential for proper response to DNA double-strand breaks in lymphocytes. J Immunol. 2007;178:103–10.PubMed

Tothova Z, Kollipara R, Huntly BJ, Lee BH, Castrillon DH, Cullen DE, McDowell EP, Lazo-Kallanian S, Williams IR, Sears C, Armstrong SA, Passegue E, DePinho RA, Gilliland DG. FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell. 2007;128:325–39.PubMedCrossRef

Wang Y, Liu L, Pazhanisamy SK, Li H, Meng A, Zhou D. Total body irradiation causes residual bone marrow injury by induction of persistent oxidative stress in murine hematopoietic stem cells. Free Radic Biol Med. 2010;48:348–56.PubMedCrossRef

Cho J, Shen H, Yu H, Li H, Cheng T, Lee SB, Lee BC. Ewing sarcoma gene Ews regulates hematopoietic stem cell senescence. Blood. 2011;117:1156–66.PubMedCrossRef

Liu J, Cao L, Chen J, Song S, Lee IH, Quijano C, Liu H, Keyvanfar K, Chen H, Cao LY, Ahn BH, Kumar NG, Rovira II, Xu XL, van Lohuizen M, Motoyama N, Deng CX, Finkel T. Bmi1 regulates mitochondrial function and the DNA damage response pathway. Nature. 2009;459:387–92.PubMedCrossRef

10.

Miyamoto K, Araki KY, Naka K, Arai F, Takubo K, Yamazaki S, Matsuoka S, Miyamoto T, Ito K, Ohmura M, Chen C, Hosokawa K, Nakauchi H, Nakayama K, Nakayama KI, Harada M, Motoyama N, Suda T, Hirao A. Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell. 2007;1:101–12.PubMedCrossRef

11.

Yalcin S, Zhang X, Luciano JP, Mungamuri SK, Marinkovic D, Vercherat C, Sarkar A, Grisotto M, Taneja R, Ghaffari S. Foxo3 is essential for the regulation of ataxia telangiectasia mutated and oxidative stress-mediated homeostasis of hematopoietic stem cells. J Biol Chem. 2008;283:25692–705.PubMedCrossRef

12.

Reya T. Regulation of hematopoietic stem cell self-renewal. Recent Prog Horm Res. 2003;58:283–95.PubMedCrossRef

13.

Weissman IL, Anderson DJ, Gage F. Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations. Annu Rev Cell Dev Biol. 2001;17:387–403.PubMedCrossRef

14.

Wilson A, Laurenti E, Trumpp A. Balancing dormant and self-renewing hematopoietic stem cells. Curr Opin Genet Dev. 2009;19:461–8.PubMedCrossRef

15.

Wang Y, Schulte BA, Zhou D. Hematopoietic stem cell senescence and long-term bone marrow injury. Cell Cycle. 2006;5:35–8.PubMedCrossRef

16.

Arai F, Suda T. Maintenance of quiescent hematopoietic stem cells in the osteoblastic niche. Ann N Y Acad Sci. 2007;1106:41–53.PubMedCrossRef

17.

Li L, Xie T. Stem cell niche: structure and function. Annu Rev Cell Dev Biol. 2005;21:605–31.PubMedCrossRef

18.

Wilson A, Oser GM, Jaworski M, Blanco-Bose WE, Laurenti E, Adolphe C, Essers MA, Macdonald HR, Trumpp A. Dormant and self-renewing hematopoietic stem cells and their niches. Ann N Y Acad Sci. 2007;1106:64–75.PubMedCrossRef

19.

Rossi DJ, Jamieson CH, Weissman IL. Stems cells and the pathways to aging and cancer. Cell. 2008;132:681–96.PubMedCrossRef

20.

Eliasson P, Jonsson JI. The hematopoietic stem cell niche: low in oxygen but a nice place to be. J Cell Physiol. 2010;222:17–22.PubMedCrossRef

21.

Parmar K, Mauch P, Vergilio JA, Sackstein R, Down JD. Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. Proc Natl Acad Sci USA. 2007;104:5431–6.PubMedCrossRef

22.

Winkler IG, Barbier V, Wadley R, Zannettino AC, Williams S, Levesque JP. Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: serially reconstituting hematopoietic stem cells reside in distinct nonperfused niches. Blood. 2010;116:375–85.PubMedCrossRef

23.

Simsek T, Kocabas F, Zheng J, Deberardinis RJ, Mahmoud AI, Olson EN, Schneider JW, Zhang CC, Sadek HA. The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche. Cell Stem Cell. 2010;7:380–90.PubMedCrossRef

24.

Takubo K, Goda N, Yamada W, Iriuchishima H, Ikeda E, Kubota Y, Shima H, Johnson RS, Hirao A, Suematsu M, Suda T. Regulation of the HIF-1alpha level is essential for hematopoietic stem cells. Cell Stem Cell. 2010;7:391–402.PubMedCrossRef

25.

Jang YY, Sharkis SJ. A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche. Blood. 2007;110:3056–63.PubMedCrossRef

26.

Danet GH, Pan Y, Luongo JL, Bonnet DA, Simon MC. Expansion of human SCID-repopulating cells under hypoxic conditions. J Clin Invest. 2003;112:126–35.PubMed

27.

Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL, Morrison SJ, Clarke MF. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature. 2003;423:302–5.PubMedCrossRef

28.

Schuringa JJ, Vellenga E. Role of the polycomb group gene BMI1 in normal and leukemic hematopoietic stem and progenitor cells. Curr Opin Hematol. 2010;17:294–9.PubMedCrossRef

29.

Abbas HA, Maccio DR, Coskun S, Jackson JG, Hazen AL, Sills TM, You MJ, Hirschi KK, Lozano G. Mdm2 is required for survival of hematopoietic stem cells/progenitors via dampening of ROS-induced p53 activity. Cell Stem Cell. 2010;7:606–17.PubMedCrossRef

30.

Chen C, Liu Y, Liu R, Ikenoue T, Guan KL, Liu Y, Zheng P. TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J Exp Med. 2008;205:2397–408.PubMedCrossRef

31.

Du W, Adam Z, Rani R, Zhang X, Pang Q. Oxidative stress in Fanconi anemia hematopoiesis and disease progression. Antioxid Redox Signal. 2008;10:1909–21.PubMedCrossRef

32.

Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005;120:483–95.PubMedCrossRef

33.

Piccoli C, Ria R, Scrima R, Cela O, D’Aprile A, Boffoli D, Falzetti F, Tabilio A, Capitanio N. Characterization of mitochondrial and extra-mitochondrial oxygen consuming reactions in human hematopoietic stem cells. Novel evidence of the occurrence of NAD(P)H oxidase activity. J Biol Chem. 2005;280:26467–76.PubMedCrossRef

34.

Piccoli C, D’Aprile A, Ripoli M, Scrima R, Lecce L, Boffoli D, Tabilio A, Capitanio N. Bone-marrow derived hematopoietic stem/progenitor cells express multiple isoforms of NADPH oxidase and produce constitutively reactive oxygen species. Biochem Biophys Res Commun. 2007;353:965–72.PubMedCrossRef

35.

Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87:245–313.PubMedCrossRef

36.

Lambeth JD. Nox enzymes, ROS, and chronic disease: an example of antagonistic pleiotropy. Free Radic Biol Med. 2007;43:332–47.PubMedCrossRef

37.

Serrander L, Cartier L, Bedard K, Banfi B, Lardy B, Plastre O, Sienkiewicz A, Forro L, Schlegel W, Krause KH. NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS generation. Biochem J. 2007;406:105–14.PubMedCrossRef

38.

Kinder M, Wei C, Shelat SG, Kundu M, Zhao L, Blair IA, Pure E. Hematopoietic stem cell function requires 12/15-lipoxygenase-dependent fatty acid metabolism. Blood. 2010;115:5012–22.PubMedCrossRef

39.

Juntilla MM, Patil VD, Calamito M, Joshi RP, Birnbaum MJ, Koretzky GA. AKT1 and AKT2 maintain hematopoietic stem cell function by regulating reactive oxygen species. Blood. 2010;115:4030–8.PubMed

40.

Lewandowski D, Barroca V, Duconge F, Bayer J, Van Nhieu JT, Pestourie C, Fouchet P, Tavitian B, Romeo PH. In vivo cellular imaging pinpoints the role of reactive oxygen species in the early steps of adult hematopoietic reconstitution. Blood. 2010;115:443–52.PubMedCrossRef

41.

Owusu-Ansah E, Banerjee U. Reactive oxygen species prime Drosophila haematopoietic progenitors for differentiation. Nature. 2009;461:537–41.PubMedCrossRef

42.

Pazhanisamy SK, Li H, Wang Y, Batinic-Haberle I, Zhou D. NADPH oxidase inhibition attenuates total body irradiation-induced haematopoietic genomic instability. Mutagenesis. 2011. doi:10.1093/mutage/ger001 [First published online: March 17, 2011].

43.

Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem. 2004;73:39–85.PubMedCrossRef

44.

von Zglinicki T, Saretzki G, Ladhoff J, d’Adda di Fagagna F, Jackson SP. Human cell senescence as a DNA damage response. Mech Ageing Dev. 2005;126:111–7.CrossRef

45.

Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res. 1965;37:614–36.PubMedCrossRef

46.

Campisi J, Kim SH, Lim CS, Rubio M. Cellular senescence, cancer and aging: the telomere connection. Exp Gerontol. 2001;36:1619–37.PubMedCrossRef

47.

Marcotte R, Wang E. Replicative senescence revisited. J Gerontol A Biol Sci Med Sci. 2002;57:B257–69.PubMedCrossRef

48.

Allsopp RC, Morin GB, DePinho R, Harley CB, Weissman IL. Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation. Blood. 2003;102:517–20.PubMedCrossRef

49.

Goytisolo FA, Samper E, Martin-Caballero J, Finnon P, Herrera E, Flores JM, Bouffler SD, Blasco MA. Short telomeres result in organismal hypersensitivity to ionizing radiation in mammals. J Exp Med. 2000;192:1625–36.PubMedCrossRef

50.

Greenwood MJ, Lansdorp PM. Telomeres, telomerase, and hematopoietic stem cell biology. Arch Med Res. 2003;34:489–95.PubMedCrossRef

51.

Samper E, Fernandez P, Eguia R, Martin-Rivera L, Bernad A, Blasco MA, Aracil M. Long-term repopulating ability of telomerase-deficient murine hematopoietic stem cells. Blood. 2002;99:2767–75.PubMedCrossRef

52.

Yamaguchi H, Calado RT, Ly H, Kajigaya S, Baerlocher GM, Chanock SJ, Lansdorp PM, Young NS. Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N Engl J Med. 2005;352:1413–24.PubMedCrossRef

53.

Allsopp RC, Morin GB, Horner JW, DePinho R, Harley CB, Weissman IL. Effect of TERT over-expression on the long-term transplantation capacity of hematopoietic stem cells. Nat Med. 2003;9:369–71.PubMedCrossRef

54.

Allsopp RC, Weissman IL. Replicative senescence of hematopoietic stem cells during serial transplantation: does telomere shortening play a role? Oncogene. 2002;21:3270–3.PubMedCrossRef

55.

Effros RB, Globerson A. Hematopoietic cells and replicative senescence. Exp Gerontol. 2002;37:191–6.PubMedCrossRef

56.

Serrano M, Blasco MA. Putting the stress on senescence. Curr Opin Cell Biol. 2001;13:748–53.PubMedCrossRef

57.

Lessard J, Sauvageau G. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature. 2003;423:255–60.PubMedCrossRef

58.

Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF, Morrison SJ. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature. 2003;425:962–7.PubMedCrossRef

59.

Wang Y, Schulte BA, LaRue AC, Ogawa M, Zhou D. Total body irradiation selectively induces murine hematopoietic stem cell senescence. Blood. 2006;107:358–66.PubMedCrossRef

60.

Lowe SW, Sherr CJ. Tumor suppression by Ink4a-Arf: progress and puzzles. Curr Opin Genet Dev. 2003;13:77–83.PubMedCrossRef

61.

Sharpless NE, DePinho RA. The INK4A/ARF locus and its two gene products. Curr Opin Genet Dev. 1999;9:22–30.PubMedCrossRef

62.

Narita M, Nunez S, Heard E, Narita M, Lin AW, Hearn SA, Spector DL, Hannon GJ, Lowe SW. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell. 2003;113:703–16.PubMedCrossRef

63.

Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell. 2005;120:513–22.PubMedCrossRef

64.

Robles SJ, Adami GR. Agents that cause DNA double strand breaks lead to p16INK4a enrichment and the premature senescence of normal fibroblasts. Oncogene. 1998;16:1113–23.PubMedCrossRef

65.

te Poele RH, Okorokov AL, Jardine L, Cummings J, Joel SP. DNA damage is able to induce senescence in tumor cells in vitro and in vivo. Cancer Res. 2002;62:1876–83.PubMed

66.

Beausejour CM, Krtolica A, Galimi F, Narita M, Lowe SW, Yaswen P, Campisi J. Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO J. 2003;22:4212–22.PubMedCrossRef

67.

Meng A, Wang Y, Van ZG, Zhou D. Ionizing radiation and busulfan induce premature senescence in murine bone marrow hematopoietic cells. Cancer Res. 2003;63:5414–9.PubMed

68.

Sherr CJ, Weber JD. The ARF/p53 pathway. Curr Opin Genet Dev. 2000;10:94–9.PubMedCrossRef

69.

Lewis JL, Chinswangwatanakul W, Zheng B, Marley SB, Nguyen DX, Cross NC, Banerji L, Glassford J, Thomas NS, Goldman JM, Lam EW, Gordon MY. The influence of INK4 proteins on growth and self-renewal kinetics of hematopoietic progenitor cells. Blood. 2001;97:2604–10.PubMedCrossRef

70.

Stepanova L, Sorrentino BP. A limited role for p16Ink4a and p19Arf in the loss of hematopoietic stem cells during proliferative stress. Blood. 2005;106:827–32.PubMedCrossRef

71.

Janzen V, Forkert R, Fleming HE, Saito Y, Waring MT, Dombkowski DM, Cheng T, DePinho RA, Sharpless NE, Scadden DT. Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature. 2006;443:421–6.PubMed

72.

Kyriakis JM, Avruch J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. 2001;81:807–69.PubMed

73.

Deng Q, Liao R, Wu BL, Sun P. High intensity ras signaling induces premature senescence by activating p38 pathway in primary human fibroblasts. J Biol Chem. 2004;279:1050–9.PubMedCrossRef

74.

Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell. 1997;88:593–602.PubMedCrossRef

75.

Zhu J, Woods D, McMahon M, Bishop JM. Senescence of human fibroblasts induced by oncogenic Raf. Genes Dev. 1998;12:2997–3007.PubMedCrossRef

76.

Iwasa H, Han J, Ishikawa F. Mitogen-activated protein kinase p38 defines the common senescence-signalling pathway. Genes Cells. 2003;8:131–44.PubMedCrossRef

77.

Haq R, Brenton JD, Takahashi M, Finan D, Finkielsztein A, Damaraju S, Rottapel R, Zanke B. Constitutive p38HOG mitogen-activated protein kinase activation induces permanent cell cycle arrest and senescence. Cancer Res. 2002;62:5076–82.PubMed

78.

Wang W, Chen JX, Liao R, Deng Q, Zhou JJ, Huang S, Sun P. Sequential activation of the MEK-extracellular signal-regulated kinase and MKK3/6-p38 mitogen-activated protein kinase pathways mediates oncogenic ras-induced premature senescence. Mol Cell Biol. 2002;22:3389–403.PubMedCrossRef

79.

Katsoulidis E, Li Y, Yoon P, Sassano A, Altman J, Kannan-Thulasiraman P, Balasubramanian L, Parmar S, Varga J, Tallman MS, Verma A, Platanias LC. Role of the p38 mitogen-activated protein kinase pathway in cytokine-mediated hematopoietic suppression in myelodysplastic syndromes. Cancer Res. 2005;65:9029–37.PubMedCrossRef

80.

Verma A, Deb DK, Sassano A, Kambhampati S, Wickrema A, Uddin S, Mohindru M, Van BK, Platanias LC. Cutting edge: activation of the p38 mitogen-activated protein kinase signaling pathway mediates cytokine-induced hemopoietic suppression in aplastic anemia. J Immunol. 2002;168:5984–8.PubMed

81.

Voncken JW, Niessen H, Neufeld B, Rennefahrt U, Dahlmans V, Kubben N, Holzer B, Ludwig S, Rapp UR. MAPKAP kinase 3pK phosphorylates and regulates chromatin association of the polycomb group protein Bmi1. J Biol Chem. 2005;280:5178–87.PubMedCrossRef

82.

Hara E, Smith R, Parry D, Tahara H, Stone S, Peters G. Regulation of p16CDKN2 expression and its implications for cell immortalization and senescence. Mol Cell Biol. 1996;16:859–67.PubMed

83.

Wang W, Martindale JL, Yang X, Chrest FJ, Gorospe M. Increased stability of the p16 mRNA with replicative senescence. EMBO Rep. 2005;6:158–64.PubMedCrossRef

84.

Dean JL, Sully G, Clark AR, Saklatvala J. The involvement of AU-rich element-binding proteins in p38 mitogen-activated protein kinase pathway-mediated mRNA stabilisation. Cell Signal. 2004;16:1113–21.PubMedCrossRef

85.

Gaestel M. MAPKAP kinases—MKs—two’s company, three’s a crowd. Nat Rev Mol Cell Biol. 2006;7:120–30.PubMedCrossRef

Titel: Reactive oxygen species and hematopoietic stem cell senescence
verfasst von: Lijian Shao
Hongliang Li
Senthil K. Pazhanisamy
Aimin Meng
Yong Wang
Daohong Zhou
Publikationsdatum: 01.07.2011
Verlag: Springer Japan
Erschienen in: International Journal of Hematology / Ausgabe 1/2011
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-011-0872-1

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