Skip to main content

Oxidative Stress as a Critical Determinant of Adult Cardiac Progenitor Cell-Fate Decisions

  • Chapter
  • First Online:
Book cover Modulation of Oxidative Stress in Heart Disease

Abstract

Tissue homeostasis and the response to injury require a tight regulation of the balance between self-renewal and differentiation of adult stem/progenitor cells. Recent evidence obtained in several tissues suggests that this balance is regulated, at least in part, by the cellular redox status via the control of reactive oxygen species (ROS) levels and cellular metabolism. In this chapter, we consider the main sources and the relevance of oxidative stress in adult stem turnover and the key signaling pathways involved, with a particular focus on cardiac progenitor cell turnover. While it is generally accepted that the mammalian heart has high physiological levels of ROS and an oxidative metabolism, few studies have explored the importance of redox signaling in cardiac progenitor cells. We propose that low-ROS areas in the heart are permissive niches for adult cardiac progenitor cells. Accordingly, manipulation of ROS-related signaling pathways in the adult heart might open new horizons for stem cell therapy by enhancing their heretofore limited cardiac regenerative potential.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Dröge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95

    PubMed  Google Scholar 

  2. Chandel NS, Maltepe E, Goldwasser E et al (1998) Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci U S A 95:11715–11720

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Nemoto S, Takeda K, Yu ZX et al (2000) Role for mitochondrial oxidants as regulators of cellular metabolism. Mol Cell Biol 20:7311–7318

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Kitamoto K, Miura Y, Karnan S et al (2018) Inhibition of NADPH oxidase 2 induces apoptosis in osteosarcoma: the role of reactive oxygen species in cell proliferation. Oncol Lett 15:7955–7962

    PubMed  PubMed Central  Google Scholar 

  5. Lee SH, Kim JK, Jang HD (2014) Genistein inhibits osteoclastic differentiation of RAW 264.7 cells via regulation of ROS production and scavenging. Int J Mol Sci 15:10605–10621

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Hou G, Zhao H, Teng H et al (2018) N-cadherin attenuates high glucose-induced nucleus pulposus cell senescence through regulation of the ROS/NF-κB pathway. Cell Physiol Biochem 47:257–265

    CAS  PubMed  Google Scholar 

  7. Sulciner DJ, Irani K, Yu ZX et al (1996) Rac1 regulates a cytokine-stimulated, redox-dependent pathway necessary for NF-kappaB activation. Mol Cell Biol 16:7115–7121

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Mathew R, Karp CM, Beaudoin B et al (2009) Autophagy suppresses tumorigenesis through elimination of p62. Cell 137:1062–1075

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Herrero D, Tomé M, Cañón S et al (2018) Redox-dependent BMI1 activity drives in vivo adult cardiac progenitor cell differentiation. Cell Death Differ 25:807–820

    PubMed Central  Google Scholar 

  10. Kim JH, Song SY, Park SG et al (2012) Primary involvement of NADPH oxidase 4 in hypoxia-induced generation of reactive oxygen species in adipose-derived stem cells. Stem Cells Dev 21:2212–2221

    CAS  PubMed  Google Scholar 

  11. Borodkina A, Shatrova A, Abushik P et al (2014) Interaction between ROS dependent DNA damage, mitochondria and p38 MAPK underlies senescence of human adult stem cells. Aging 6:481–495

    PubMed  PubMed Central  Google Scholar 

  12. Shi B, Wang Y, Zhao R et al (2018) Bone marrow mesenchymal stem cell-derived exoso-mal miR-21 protects C-kit+ cardiac stem cells from oxidative injury through the PTEN/PI3K/Akt axis. PLoS One 13:e0191616

    PubMed  PubMed Central  Google Scholar 

  13. Varum S, Rodrigues AS, Moura MB et al (2011) Energy metabolism in human pluripotent stem cells and their differentiated counterparts. PLoS One 6:e20914

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Saretzki G, Armstrong L, Leake A et al (2004) Stress defense in murine embryonic stem cells is superior to that of various differentiated murine cells. Stem Cells 22:962–971

    CAS  PubMed  Google Scholar 

  15. Schmelter M, Ateghang B, Helmig S et al (2006) Embryonic stem cells utilize reactive oxygen species as transducers of mechanical strain-induced cardiovascular differentiation. FASEB J 20:1182–1184

    CAS  PubMed  Google Scholar 

  16. Ji AR, Ku SY, Cho MS et al (2010) Reactive oxygen species enhance differentiation of human embryonic stem cells into mesendodermal lineage. Exp Mol Med 42:175–186

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Brand MD (2010) The sites and topology of mitochondrial superoxide production. Exp Gerontol 45:466–472

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Aon MA, Stanley BA, Sivakumaran V et al (2012) Glutathione/thioredoxin systems modu-late mitochondrial H2O2 emission: an experimental-computational study. J Gen Physiol 139:479–491

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Tahara EB, Navarete FD, Kowaltowski AJ (2009) Tissue-, substrate-, and site-specific characteristics of mitochondrial reactive oxygen species generation. Free Radic Biol Med 46:1283–1297

    CAS  PubMed  Google Scholar 

  20. Lapuente-Brun E, Moreno-Loshuertos R, Acín-Pérez R et al (2013) Supercomplex assem-bly determines electron flux in the mitochondrial electron transport chain. Science 340:1567–1570

    CAS  PubMed  Google Scholar 

  21. Drahota Z, Chowdhury SK, Floryk D et al (2002) Glycerophosphate-dependent hydrogen peroxide production by brown adipose tissue mitochondria and its activation by ferricyanide. J Bioenerg Biomembr 34:105–113

    CAS  PubMed  Google Scholar 

  22. Frerman FE (1987) Reaction of electron-transfer flavoprotein ubiquinone oxidoreductase with the mitochondrial respiratory chain. Biochim Biophys Acta 893:161–169

    CAS  PubMed  Google Scholar 

  23. Vasquez-Vivar J, Kalyanaraman B, Kennedy MC (2000) Mitochondrial aconitase is a source of hydroxyl radical. An electron spin resonance investigation. J Biol Chem 275:14064–14069

    CAS  PubMed  Google Scholar 

  24. Hauptmann N, Grimsby J, Shih JC et al (1996) The metabolism of tyramine by monoamine oxidase A/B causes oxidative damage to mitochondrial DNA. Arch Biochem Biophys 335:295–304

    CAS  PubMed  Google Scholar 

  25. Giorgio M, Migliaccio E, Orsini F et al (2005) Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis. Cell 122:221–233

    CAS  PubMed  Google Scholar 

  26. Tothova Z, Kollipara R, Huntly BJ et al (2007) FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell 128:325–339

    CAS  PubMed  Google Scholar 

  27. Sansone P, Storci G, Giovannini C et al (2007) p66Shc/Notch-3 interplay controls self-renewal and hypoxia survival in human stem/progenitor cells of the mammary gland expanded in vitro as mammospheres. Stem Cells 25:807–815

    CAS  PubMed  Google Scholar 

  28. Starkov AA, Fiskum G, Chinopoulos C et al (2004) Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen species. J Neurosci 24:7779–7788

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Prigione A, Fauler B, Lurz R et al (2010) The senescence-related mitochondrial/oxidative stress pathway is repressed in human induced pluripotent stem cells. Stem Cells 28:721–733

    CAS  PubMed  Google Scholar 

  30. Chung S, Dzeja PP, Faustino RS et al (2007) Mitochondrial oxidative metabolism is required for the cardiac differentiation of stem cells. Nat Clin Pract Cardiovasc Med 4(Suppl 1):S60–S67

    CAS  PubMed  PubMed Central  Google Scholar 

  31. St John JC, Ramalho-Santos J, Gray HL et al (2005) The expression of mitochondrial DNA transcription factors during early cardiomyocyte in vitro differentiation from human embryonic stem cells. Cloning Stem Cells 7:141–153

    CAS  PubMed  Google Scholar 

  32. Chung S, Arrell DK, Faustino RS et al (2010) Glycolytic network restructuring integral to the energetics of embryonic stem cell cardiac differentiation. J Mol Cell Cardiol 48:725–734

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Skonieczna M, Hejmo T, Poterala-Hejmo A et al (2017) NADPH oxidases: insights into selected functions and mechanisms of action in cancer and stem cells. Oxidative Med Cell Longev 2017:9420539

    Google Scholar 

  34. Li J, Stouffs M, Serrander L et al (2006) The NADPH oxidase NOX4 drives cardiac differentiation: role in regulating cardiac transcription factors and MAP kinase activation. Mol Biol Cell 17:3978–3988

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Nadworny AS, Guruju MR, Poor D et al (2013) Nox2 and Nox4 influence neonatal c-kit(+) cardiac precursor cell status and differentiation. Am J Physiol Heart Circ Physiol 305:H829–H842

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Topchiy E, Panzhinskiy E, Griffin WS (2013) Nox4-generated superoxide drives angiotensin II-induced neural stem cell proliferation. Dev Neurosci 35:293–305

    CAS  PubMed  Google Scholar 

  37. Moruno-Manchon JF, Uzor NE, Kesler SR et al (2018) Peroxisomes contribute to oxidative stress in neurons during doxorubicin-based chemotherapy. Mol Cell Neurosci 86:65–71

    CAS  PubMed  Google Scholar 

  38. Jiang S, He R, Zhu L et al (2018) Endoplasmic reticulum stress-dependent ROS production mediates synovial myofibroblastic differentiation in the immobilization-induced rat knee joint contracture model. Exp Cell Res S0014-4827(18):30316–30311

    Google Scholar 

  39. Zangar RC, Davydov DR, Verma S (2004) Mechanisms that regulate production of reactive oxygen species by cytochrome P450. Toxicol Appl Pharmacol 199:316–331

    CAS  PubMed  Google Scholar 

  40. Chuang DY, Simonyi A, Kotzbauer PT et al (2015) Cytosolic phospholipase A2 plays a crucial role in ROS/NO signaling during microglial activation through the lipoxygenase pathway. J Neuroinflammation 12:199

    PubMed  PubMed Central  Google Scholar 

  41. Huang CC, Chen KL, Cheung CH et al (2013) Autophagy induced by cathepsin S inhibition induces early ROS production, oxidative DNA damage, and cell death via xanthine oxidase. Free Radic Biol Med 65:1473–1486

    CAS  PubMed  Google Scholar 

  42. He L, He T, Farrar S et al (2017) Antioxidants maintain cellular redox homeostasis by elimination of reactive oxygen species. Cell Physiol Biochem 44:532–553

    PubMed  Google Scholar 

  43. Dernbach E, Urbich C, Brandes RP et al (2004) Antioxidative stress-associated genes in circulating progenitor cells: evidence for enhanced resistance against oxidative stress. Blood 104:3591–3597

    CAS  PubMed  Google Scholar 

  44. Bognar Z, Kalai T, Palfi A et al (2006) A novel SOD-mimetic permeability transition inhibitor agent protects ischemic heart by inhibiting both apoptotic and necrotic cell death. Free Radic Biol Med 41:835–848

    CAS  PubMed  Google Scholar 

  45. Saretzki G, Walter T, Atkinson S et al (2008) Downregulation of multiple stress defense mechanisms during differentiation of human embryonic stem cells. Stem Cells 26:455–464

    CAS  PubMed  Google Scholar 

  46. Solari C, Vázquez Echegaray C, Cosentino MS et al (2015) Manganese superoxide dismutase gene expression is induced by nanog and Oct4, essential pluripotent stem cells’ transcription factors. PLoS One 10:e0144336

    PubMed  PubMed Central  Google Scholar 

  47. Miao W, Xufeng R, Park MR et al (2013) Hematopoietic stem cell regeneration enhanced by ectopic expression of ROS-detoxifying enzymes in transplant mice. Mol Ther 21:423–432

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Kwon T, Bak Y, Park YH et al (2016) Peroxiredoxin II is essential for maintaining stemness by redox regulation in liver cancer cells. Stem Cells 34:1188–1197

    CAS  PubMed  Google Scholar 

  49. Spradling A, Drummond-Barbosa D, Kai T (2001) STem cells find their niche. Nature 414:98–104

    CAS  PubMed  Google Scholar 

  50. Simon MC, Keith B (2008) The role of oxygen availability in embryonic development and stem cell function. Nat Rev Mol Cell Biol 9:285–296

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Panchision DM (2009) The role of oxygen in regulating neural stem cells in development and disease. J Cell Physiol 220:562–568

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  53. Silván U, Díez-Torre A, Arluzea J et al (2009) Hypoxia and pluripotency in embryonic and embryonal carcinoma stem cell biology. Differentiation 78:159–168

    PubMed  Google Scholar 

  54. Cho YM, Kwon S, Pak YK et al (2006) LeeDynamic changes in mitochondrial biogenesis and antioxidant enzymes during the spontaneous differentiation of human embryonic stem cells. Biochem Biophys Res Commun 348:1472–1478

    CAS  PubMed  Google Scholar 

  55. Wang K, Zhang T, Dong Q et al (2013) Redox homeostasis: the linchpin in stem cell self-renewal and differentiation. Cell Death Dis 4:e537

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Gardner LB, Li Q, Park MS et al (2001) Hypoxia inhibits G1/S transition through regulation of p27 expression. J Biol Chem 276:7919–7926

    CAS  PubMed  Google Scholar 

  57. Iida T, Mine S, Fujimoto H et al (2002) Hypoxia-inducible factor-1alpha induces cell cycle arrest of endothelial cells. Genes Cells 7:143–149

    CAS  PubMed  Google Scholar 

  58. Koshiji M, Kageyama Y, Pete EA et al (2004) HIF-1alpha induces cell cycle arrest by functionally counteracting Myc. EMBO J 23:1949–1956

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Adelman DM, Gertsenstein M, Nagy A et al (2000) Placental cell fates are regulated in vivo by HIF-mediated hypoxia responses. Genes Dev 14:3191–3203

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Lee SW, Jeong HK, Lee JY et al (2012) Hypoxic priming of mESCs accelerates vascular-lineage differentiation through HIF1-mediated inverse regulation of Oct4 and VEGF. EMBO Mol Med 4:924–938

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Francis KR, Wei L (2010) Human embryonic stem cell neural differentiation and enhanced cell survival promoted by hypoxic preconditioning. Cell Death Dis 1:e22

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Ng KM, Lee YK, Chan YC et al (2010) Exogenous expression of HIF-1 alpha promotes cardiac differentiation of embryonic stem cells. J Mol Cell Cardiol 48:1129–1137

    CAS  PubMed  Google Scholar 

  63. De Miguel MP, Alcaina Y, de la Maza DS et al (2015) Cell metabolism under microenvironmental low oxygen tension levels in stemness, proliferation and pluripotency. Curr Mol Med 15:343–359

    PubMed  Google Scholar 

  64. Gustafsson MV, Zheng X, Pereira T et al (2005) Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev Cell 9:617–628

    CAS  PubMed  Google Scholar 

  65. Mutoh TS (2012) Oxygen levels epigenetically regulate fate switching of neural precursor cells via hypoxia-inducible factor 1α-notch signal interaction in the developing brain. Stem Cells 30:561–569

    CAS  PubMed  Google Scholar 

  66. Covello KL, Kehler J, Yu H et al (2006) HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes Dev 20:557–570

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Kaidi A, Williams AC, Paraskeva C (2007) Interaction between beta-catenin and HIF-1 promotes cellular adaptation to hypoxia. Nat Cell Biol 9:210–217

    CAS  PubMed  Google Scholar 

  68. Takubo K, Goda N, Yamada W et al (2010) Regulation of the HIF-1alpha level is essential for hematopoietic stem cells. Cell Stem Cell 7:391–402

    CAS  PubMed  Google Scholar 

  69. Zhang K, Zhou Y, Zhao T et al (2015) Reduced cerebral oxygen content in the DG and SVZ in situ promotes neurogenesis in the adult rat brain in vivo. PLoS One 10:e0140035

    PubMed  PubMed Central  Google Scholar 

  70. Lange C, Turrero-Garcia M, Decimo I et al (2016) Relief of hypoxia by angiogenesis promotes neural stem cell differentiation by targeting glycolysis. EMBO J 35:924–941

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Li L, Candelario KM, Thomas K et al (2014) Hypoxia inducible factor-1α (HIF-1α) is required for neural stem cell maintenance and vascular stability in the adult mouse SVZ. J Neurosci 34:16713–16719

    PubMed  PubMed Central  Google Scholar 

  72. Estrada JC, Albo C, Benguría A et al (2012) Culture of human mesenchymal stem cells at low oxygen tension improves growth and genetic stability by activating glycolysis. Cell Death Differ 19:743–755

    CAS  PubMed  Google Scholar 

  73. Valorani MG, Montelatici E, Germani A et al (2012) Pre-culturing human adipose tissue mesenchymal stem cells under hypoxia increases their adipogenic and osteogenic differentiation potentials. Cell Prolif 45:225–238

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Ateghang B, Wartenberg M, Gassmann M et al (2006) Regulation of cardiotrophin-1 expression in mouse embryonic stem cells by HIF-1α and intracellular reactive oxygen species. J Cell Sci 119:1043–1052

    CAS  PubMed  Google Scholar 

  75. Salih DA, Brunet A (2008) FoxO transcription factors in the maintenance of cellular homeostasis during aging. Curr Opin Cell Biol 20:126–136

    CAS  PubMed  PubMed Central  Google Scholar 

  76. van der Horst A, Burgering BM (2007) Stressing the role of FoxO proteins in lifespan and disease. Nat Rev Mol Cell Biol 8:440–450

    PubMed  Google Scholar 

  77. Essers MA, de Vries-Smits LM, Barker N et al (2005) Functional interaction between beta-catenin and FOXO in oxidative stress signaling. Science 308:1181–1184

    CAS  PubMed  Google Scholar 

  78. Kops GJ, Dansen TB, Polderman PE et al (2002) Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature 419:316–321

    CAS  PubMed  Google Scholar 

  79. Paik JH, Ding Z, Narurkar R et al (2009) FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis. Cell Stem Cell 5:540–553

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Miyamoto K, Araki KY, Naka K et al (2007) Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell 1:101–112

    CAS  PubMed  Google Scholar 

  81. Miyamoto K, Miyamoto T, Kato R et al (2008) FoxO3a regulates hematopoietic homeostasis through a negative feedback pathway in conditions of stress or aging. Blood 112:4485–4493

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Iyer S, Ambrogini E, Bartell SM et al (2013) FOXOs attenuate bone formation by suppressing Wnt signaling. J Clin Invest 123:3409–3419

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Higuchi M, Dusting GJ, Peshavariya H et al (2013) Differentiation of human adipose -derived stem cells into fat involves reactive oxygen species and Forkhead box O1 mediated upregulation of antioxidant enzymes. Stem Cells Dev 22:878–888

    CAS  PubMed  Google Scholar 

  84. Zhang X, Yalcin S, Lee DF et al (2011) FOXO1 is an essential regulator of pluripotency in human embryonic stem cells. Nat Cell Biol 13:1092–1099

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Nguyen T, Nioi P, Pickett CB (2009) The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem 284:13291–13295

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Itoh K, Wakabayashi N, Katoh Y et al (1999) Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev 13:76–86

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Kobayashi A, Kang MI, Okawa H et al (2004) Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol Cell Biol 24:7130–7139

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Li J, Johnson D, Calkins M et al (2005) Stabilization of Nrf2 by tBHQ confers protection against oxidative stress-induced cell death in human neural stem cells. Toxicol Sci 83:313–328

    CAS  PubMed  Google Scholar 

  89. Tsai JJ, Dudakov JA, Takahashi K et al (2013) Nrf2 regulates haematopoietic stem cell function. Nat Cell Biol 15:309–316

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Murakami S, Suzuki T, Harigae H et al (2017) NRF2 activation impairs quiescence and bone marrow reconstitution capacity of hematopoietic stem cells. Mol Cell Biol 37:e00086–e00017

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Jang J, Wang Y, Kim HS et al (2014) Nrf2, a regulator of the proteasome, controls self-renewal and pluripotency in human embryonic stem cells. Stem Cells 32:2616–2625

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Mohammadzadeh M, Halabian R, Gharehbaghian A et al (2012) Nrf-2 overexpression in mesenchymal stem cells reduces oxidative stress-induced apoptosis and cytotoxicity. Cell Stress Chaperones 17:553–565

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Yoon DS, Choi Y, Lee JW (2016) Cellular localization of NRF2 determines the self-renewal and osteogenic differentiation potential of human MSCs via the P53–SIRT1 axis. Cell Death Dis 7:e2093

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Bhattacharya R, Mustafi SB, Street M et al (2015) Bmi-1: at the crossroads of physiological and pathological biology. Genes Dis 2:225–239

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Pietersen AM, van Lohuizen M (2008) Stem cell regulation by polycomb repressors: postponing commitment. Curr Opin Cell Biol 20:201–217

    CAS  PubMed  Google Scholar 

  96. Molofsky AV, Pardal R, Iwashita T et al (2003) Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425:962–967

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Park IK, Qian D, Kiel M et al (2003) Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423:302–325

    CAS  PubMed  Google Scholar 

  98. López-Arribillaga E, Rodilla V, Pellegrinet L et al (2015) Bmi1 regulates murine intestinal stem cell proliferation and self-renewal downstream of notch. Development 142:41–50

    PubMed  Google Scholar 

  99. Valiente-Alandi I, Albo-Castellanos C, Herrero D et al (2015) Cardiac Bmi1+ cells contribute to myocardial renewal in the murine adult heart. Stem Cell Res Ther 6:205

    PubMed  PubMed Central  Google Scholar 

  100. Liu L, Cao L, Chen J et al (2009) Bmi1 regulates mitochondrial function and the DNA damage response pathway. Nature 459:387–392

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Valiente-Alandi I, Albo-Castellanos C, Herrero D et al (2016) Bmi1 (+) cardiac progenitor cells contribute to myocardial repair following acute injury. Stem Cell Res Ther 7:100

    PubMed  PubMed Central  Google Scholar 

  102. Herrero D, Cañón S, Pelacho B et al (2018) Bmi1-progenitor cell ablation impairs the angiogenic response to myocardial infarction. Arterioscler Thromb Vasc Biol 38:2160–2173. https://doi.org/10.1161/ATVBAHA.118.310778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Brodkina A, Shatrova A, Abushik P, Nikolsky N, Burova E (2014) Interaction between ROS dependent DNA damage, mitochondria and p38 MAPK underlies senescence of human adult stem cells. Aging (Albany NY) 6:481–495

    Google Scholar 

  104. Kong Y, Song Y, Hu Y et al (2016) Increased reactive oxygen species and exhaustion of quiescent CD34-positive bone marrow cells may contribute to poor graft function after allotransplants. Oncotarget 7:30892–30906

    PubMed  PubMed Central  Google Scholar 

  105. Brien GL, Healy E, Jerman E et al (2015) A chromatin-independent role of Polycomb-like 1 to stabilize p53 and promote cellular quiescence. Genes Dev 29:2231–2243

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Mohrin M, Bourke E, Alexander D et al (2010) Hematopoietic stem cell quiescence promo-tes error-prone DNA repair and mutagenesis. Cell Stem Cell 7:174–185

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Boregowda SV, Krishnappa V, Strivelli J (2018) Basal p53 expression is indispensable for mesenchymal stem cell integrity. Cell Death Differ 25:677–690

    PubMed Central  Google Scholar 

  108. Cesselli D, Aleksova A, Sponga S et al (2017) Cardiac cell senescence and redox signaling. Front Cardiovasc Med 4:38

    PubMed  PubMed Central  Google Scholar 

  109. Khaper N, Bailey CDC, Ghugre NR et al (2018) Implications of disturbances in circadian rhythms for cardiovascular health: a new frontier in free radical biology. Free Radic Biol Med 119:85–92

    CAS  PubMed  Google Scholar 

  110. Kanaan GN, Harper ME (2017) Cellular redox dysfunction in the development of cardiovascular diseases. Biochim Biophys Acta 1861:2822–2829

    CAS  Google Scholar 

  111. He F, Zuo L (2015) Redox roles of reactive oxygen species in cardiovascular diseases. Int J Mol Sci 16:27770–27780

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Barančík M, Grešová L, Barteková M et al (2016) Nrf2 as a key player of redox regulation in cardiovascular diseases. Physiol Res 65(Suppl 1):S1–S10

    PubMed  Google Scholar 

  113. Erkens R, Kramer CM, Lückstädt W et al (2015) Left ventricular diastolic dysfunction in Nrf2 knock out mice is associated with cardiac hypertrophy, decreased expression of SERCA2a, and preserved endothelial function. Free Radic Biol Med 89:906–917

    CAS  PubMed  Google Scholar 

  114. Xu B, Zhang J, Strom J et al (2014) Myocardial ischemic reperfusion induces de novo Nrf2 protein translation. Biochim Biophys Acta 1842:1638–1647

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Taunk NK, Haffty BG, Kostis JB et al (2015) Radiation-induced heart disease: pathologic abnormalities and putative mechanisms. Front Oncol 5:39

    PubMed  PubMed Central  Google Scholar 

  116. Ahamed J, Laurence J (2017) Role of platelet-derived transforming growth factor-β1 and reactive oxygen species in radiation-induced organ fibrosis. Antioxid Redox Signal 27:977–988

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Weigel C, Schmezer P, Plass C et al (2015) Epigenetics in radiation-induced fibrosis. Oncogene 34:2145–2155

    CAS  PubMed  Google Scholar 

  118. Bergmann O, Zdunek S, Felker A et al (2015) Dynamics of cell generation and turnover in the human heart. Cell 161:1566–1575

    CAS  PubMed  Google Scholar 

  119. Uygur A, Lee RT (2016) Mechanisms of cardiac regeneration. Dev Cell 36:362–374

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Poss KD, Wilson LG, Keating MT (2002) Heart regeneration in Zebrafish. Science 298:2188–2190

    CAS  PubMed  Google Scholar 

  121. Jopling C, Sleep E, Raya M et al (2010) Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature 464:606–609

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Wang J, Panáková D, Kikuchi K et al (2011) The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion. Development 138:3421–3430

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Kikuchi K, Holdway JE, Werdich AA et al (2010) Primary contribution to zebrafish heart regeneration by Gata4+ cardiomyocytes. Nature 464:601–605

    CAS  PubMed  PubMed Central  Google Scholar 

  124. González-Rosa JM, Sharpe M, Field D et al (2018) Myocardial polyploidization creates a barrier to heart regeneration in zebrafish. Dev Cell 44:433–446

    PubMed  PubMed Central  Google Scholar 

  125. Roesner A, Hankeln T, Burmester T (2006) Hypoxia induces a complex response of globin expression in zebrafish (Danio rerio). J Exp Biol 209:2129–2137

    CAS  PubMed  Google Scholar 

  126. Rees BB, Sudradjat FA, Love JW (2001) Acclimation to hypoxia increases survival time of zebrafish, Danio rerio, during lethal hypoxia. J Exp Zool 289:266–272

    CAS  PubMed  Google Scholar 

  127. Flink IL (2002) Cell cycle reentry of ventricular and atrial cardiomyocytes and cells within the epicardium following amputation of the ventricular apex in the axolotl, Amblystoma mexicanum: confocal microscopic immunofluorescent image analysis of bromodeoxyuridine-label. Anat Embryol 205:235–244

    Google Scholar 

  128. Oberpriller JO, Oberpriller JC (1974) Response of the adult newt ventricle to injury. J Exp Zool 187:249–253

    CAS  PubMed  Google Scholar 

  129. Dawes GS, Mott JC, Widdicombe JG (1954) The foetal circulation in the lamb. J Physiol 126:563–587

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Suturzu AC, Rajarajan K, Passer D et al (2014) The fetal mammalian heart generates a robust compensatory response to cell loss. Circulation 132:109–121

    Google Scholar 

  131. Porrello ER, Mahmoud AI, Simpson E et al (2011) Transient regenerative potential of the neonatal mouse heart. Science 331:1078–1080

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Sampaio-Pinto V, Rodrigues SC, Laundos TL et al (2018) Neonatal apex resection triggers cardiomyocyte proliferation, neovascularization and functional recovery despite local fibrosis. Stem Cell Rep 10:860–874

    Google Scholar 

  133. Webster WS, Abela D (2007) The effect of hypoxia in development. Birth Defects Res C Embryo Today 81:215–228

    CAS  PubMed  Google Scholar 

  134. Puente BN, Kimura W, Muralidhar SA et al (2014) The oxygen rich postnatal environment induces cardiomyocyte cell cycle arrest through DNA damage response. Cell 157:565–579

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Millis RJ, Titmarsh DM, Koenig X et al (2017) Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest. Proc Natl Acad Sci U S A 114:E8372–E8381

    Google Scholar 

  136. Yang F, Liu YH, Yang XP et al (2002) Myocardial infarction and cardiac remodelling in mice. Exp Physiol 87:547–555

    CAS  PubMed  Google Scholar 

  137. Beltrami AP, Barlucchi L, Torella D et al (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114:763–776

    CAS  PubMed  Google Scholar 

  138. Kramann R, Schneider RK, DiRocco DP et al (2015) Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis. Cell Stem Cell 16:51–66

    CAS  PubMed  Google Scholar 

  139. Uchida S, De Gaspari P, Kostin S et al (2013) Sca1-derived cells are a source of myocardial renewal in the murine adult heart. Stem Cell Rep 1:397–410

    CAS  Google Scholar 

  140. Noseda M, Harada M, McSweeney S et al (2015) PDGFRα demarcates the cardiogenic clonogenic Sca1+ stem/progenitor cell in adult murine myocardium. Nat Commun 6:6930

    CAS  PubMed  Google Scholar 

  141. Vicinanza C, Aquila I, Scalise M et al (2017) Adult cardiac stem cells are multipotent and robustly myogenic: c-kit expression is necessary but not sufficient for their identification. Cell Death Differ 24:2101–2116

    CAS  PubMed  PubMed Central  Google Scholar 

  142. van Berlo JH, Molkentin JD (2016) Most of the dust has settled: cKit+ progenitor cells are an irrelevant source of cardiac myocytes in vivo. Circ Res 118:17–19

    PubMed  PubMed Central  Google Scholar 

  143. He L, Li Y, Li Y et al (2017) Enhancing the precision of genetic lineage tracing using dual recombinases. Nat Med 23:1488–1498

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Castaldi A, Dodia RM, Orogo AM et al (2017) Decline in cellular function of aged mouse c-kit+ cardiac progenitor cells. J Physiol 595:6249–6262

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Saheera S, Nair RR (2017) Accelerated decline in cardiac stem cell efficiency in spontaneously hypertensive rat compared to normotensive wistar rat. PLoS One 12:e0189129

    PubMed  PubMed Central  Google Scholar 

  146. Kimura W, Xiao F, Canseco DC et al (2015) Hypoxia fate mapping identifies cycling cardiomyocytes in the adult heart. Nature 523:226–230

    CAS  PubMed  Google Scholar 

  147. Shao D, Zhai P, Del Re P et al (2014) A functional interaction between hippo-YAP signalling and FoxO1 mediates the oxidative stress response. Nat Commun 5:3315

    PubMed  Google Scholar 

  148. Diez-Cuñado M, Wei K, Bushway PJ et al (2018) miRNAs that induce human cardiomyocyte proliferation converge on the hippo pathway. Cell Rep 23:2168–2174

    PubMed  PubMed Central  Google Scholar 

  149. Crespo FL, Sobrado VR, Gomez L et al (2010) Mitochondrial reactive oxygen species mediate cardiomyocyte formation from embryonic stem cells in high glucose. Stem Cells 28:1132–1142

    CAS  PubMed  Google Scholar 

  150. Sauer H, Rahimi G, Hescheler J et al (2000) Role of reactive oxygen species and phosphatidylinositol 3-kinase in cardiomyocyte differentiation of embryonic stem cells. FEBS Lett 476:218–223

    CAS  PubMed  Google Scholar 

  151. Li X, He P, Wang XL et al (2018) Sulfiredoxin-1 enhances cardiac progenitor cell survival against oxidative stress via the upregulation of the ERK/NRF2 signal pathway. Free Radic Biol Med 123:8–19

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Khatiwala RV, Zhang S, Li X et al (2018) Inhibition of p16INK4A to rejuvenate aging human cardiac progenitor cells via the upregulation of anti-oxidant and NFκB signal pathways. Stem Cell Rev 14:612–625. https://doi.org/10.1007/s12015-018-9815-z

    Article  CAS  PubMed Central  Google Scholar 

  153. Carresi C, Musolino V, Gliozzi M et al (2018) Anti-oxidant effect of bergamot polyphenolic fraction counteracts doxorubicin-induced cardiomyopathy: role of autophagy and c-kitposCD45negCD31neg cardiac stem cell activation. J Mol Cell Cardiol 119:10–18

    CAS  PubMed  Google Scholar 

  154. Seo SK, Kim N, Lee JH et al (2018) β-arrestin2 affects cardiac progenitor cell survival through cell mobility and tube formation in severe hypoxia. Korean Circ J 48:296–309

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Hernandez I, Baio JM, Tsay E et al (2018) Short-term hypoxia improves early cardiac progenitor cell function in vitro. Am J Stem Cells 7:1–17

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Amirrasouli MM, Shamsara M (2017) Comparing the in vivo and in vitro effects of hypoxia (3% O2) on directly derived cells from murine cardiac explants versus murine cardiosphere derived cells. J Stem Cells Regen Med 13:35–44

    PubMed  PubMed Central  Google Scholar 

  157. Nakada Y, Canseco DC, Thet SW et al (2017) Hypoxia induces heart regeneration in adult mice. Nature 541:222–227

    CAS  PubMed  Google Scholar 

  158. Bigarella CL, Li J, Rimmelé P et al (2014) Stem cells and the impact of ROS signaling. Development 141:4206–4218

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Sanada F, Kim J, Czarna A et al (2014) c-Kit-positive cardiac stem cells nested in hypoxic niches are activated by stem cell factor reversing the aging myopathy. Circ Res 114:41–55

    CAS  PubMed  Google Scholar 

  160. Seshadri G, Che PL, Boopathy AV et al (2012) Characterization of superoxide dismutases in cardiac progenitor cells demonstrates a critical role for manganese superoxide dismutase. Stem Cells Dev 21:3136–3146

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Krishnamurthy P, Ross DD, Nakanishi T et al (2004) The stem cell marker Bcrp/ABCG2 enhances hypoxic cell survival through interactions with heme. J Biol Chem 279:24218–22425

    CAS  PubMed  Google Scholar 

  162. Li TS, Cheng K, Malliaras K (2011) Expansion of human cardiac stem cells in physiological oxygen improves cell production efficiency and potency for myocardial repair. Cardiovasc Res 89:157–165

    CAS  PubMed  Google Scholar 

  163. Moscoso I, Tejados N, Barreiro O et al (2016) Podocalyxin-like protein 1 is a relevant marker for human c-kit(pos) cardiac stem cells. J Tissue Eng Regen Med 10:580–590

    CAS  PubMed  Google Scholar 

  164. Sanz-Ruiz R, Casado-Plasencia A, Borlado LR et al (2017) Rationale and design of a clinical trial to evaluate the safety and efficacy of intracoronary infusion of allogeneic human cardiac stem cells in patients with acute myocardial infarction and left ventricular dysfunction: the randomized multicenter double-blind controlled CAREMI trial (cardiac stem cells in patients with acute myocardial infarction). Circ Res 121:71–80

    CAS  PubMed  Google Scholar 

  165. Morrison SJ, Spradling C (2008) Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell 132:598–611

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Itkin T, Gur-Cohen S, Spencer JA et al (2016) Distinct bone marrow blood vessels differentially regulate haematopoiesis. Nature 532:323–328

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Spencer J, Ferraro F, Roussakis E et al (2014) Direct measurement of local oxygen concentration in the bone marrow of live animals. Nature 508:269–273

    CAS  PubMed  PubMed Central  Google Scholar 

  168. Kocabas F, Mahmoud AI, Sosic D et al (2012) The hypoxic epicardial and subepicardial microenvironment. J Cardiovasc Transl Res 5:654–665

    PubMed  Google Scholar 

  169. Kimura W, Muralidhar S, Canseco DC et al (2014) Redox signaling in cardiac renewal. Antioxid Redox Signal 21:1660–1673

    CAS  PubMed  PubMed Central  Google Scholar 

  170. Fioret BA, Heimfeld JD, Paik DT et al (2014) Endothelial cells contribute to generation of adult ventricular myocytes during cardiac homeostasis. Cell Rep 8:229–241

    CAS  PubMed  PubMed Central  Google Scholar 

  171. Gómez-Gaviro MV, Lovell-Badge R, Fernández-Avilés F et al (2012) The vascular stem cell niche. J Cardiovasc Transl Res 5:618–630

    PubMed  Google Scholar 

  172. Malliaras K, Ibrahim A, Tseliou E et al (2014) Stimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarction. EMBO Mol Med 6:760–777

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Herrero D, Cañón S, Albericio G, Carmona RM, Aguilar S, Mañes S, Bernad A, (2019) Age-related oxidative stress confines damage-responsive Bmi1+ cells to perivascular regions in the murine adult heart. Redox Biology 22:101156

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Financial Acknowledgment

MINECO/FEDER; SAF2015–70882-R and ISCIII; RETICS-RD12/001.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antonio Bernad .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Herrero, D. et al. (2019). Oxidative Stress as a Critical Determinant of Adult Cardiac Progenitor Cell-Fate Decisions. In: Chakraborti, S., Dhalla, N., Dikshit, M., Ganguly, N. (eds) Modulation of Oxidative Stress in Heart Disease. Springer, Singapore. https://doi.org/10.1007/978-981-13-8946-7_13

Download citation

Publish with us

Policies and ethics