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Oxidative Stress and Nitrosative Stress

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Cardiomyocytes – Active Players in Cardiac Disease

Abstract

Cardiomyocytes generate multiple forms of short half-life molecules known as reactive oxygen and reactive nitrogen species (ROS) and acting as signaling molecules (RNS). However, under certain conditions the balance between formation of oxygen radicals and degradation of them is severely affected resulting in oxidative stress that significantly contributes to cardiac dysfunction. In this chapter key molecules that trigger ROS and RNS formation in cardiomyocytes are introduced as well as mechanisms by which cardiomyocytes normally balance oxidative stress. Target molecules and the subsequent functional consequence of ROS and RNS stress will be explained. In many cases, these processes are either located in mitochondria or influence the behavior of mitochondrial function. Therefore, ROS and RNS couples mitochondrial function to key regulatory processes of cardiomyocytes, such as force generation and growth control, despite their genuine function in energy metabolism.

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References

  • Ago T, Kuroda J, Pain J, Fu C, Li H, Sadoshima J (2010) Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes. Circ Res 106:1253–1264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Afanas’ev I (2011) ROS and RNS signaling in heart disorders: could antioxidant treatment be successful? Oxid Med Cell Longev 2011:293769

    PubMed  PubMed Central  Google Scholar 

  • Anderson EJ, Lustig ME, Boyle KE, Woodlief TL, Kane DA, Lin CT, Price JW 3rd, Kang L, Rabinovitch PS, Szeto HH, Houmard JA, Cortright RN, Wasserman DH, Neufer PD (2009) Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J Clin Invest 119:573–581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andreadou I, Iliodromitis EK, Rassaf T, Schulz R, Papapetropoulos A, Ferdinandy P (2015) The role of gasotransmitters NO, H2S and CO in myocardial ischaemia/reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning. Br J Pharmacol 172:1587–1606

    Article  CAS  PubMed  Google Scholar 

  • Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120(4):483–495

    Article  CAS  PubMed  Google Scholar 

  • Berndt C, Lillig CH, Holmgren A (2007) Thiol-based mechanisms of the thioredoxin and glutaredoxin systems: Implications for diseases in the cardiovascular system. Am J Physiol Heart Circ Physiol 292:H1227–H1236

    Article  CAS  PubMed  Google Scholar 

  • Bolli R, Marbán E (1999) Molecular and cellular mechanisms of myocardial stunning. Physiol Rev 79:609–634

    CAS  PubMed  Google Scholar 

  • Bresciani G, da Cruz IB, González-Gallego J (2015) Manganese superoxide dismutase and oxidative stress modulation. Adv Clin Chem 68:87–130

    Article  PubMed  Google Scholar 

  • Brown DI, Griendling KK (2015) Regulation of signal transduction by reactive oxygen species in the cardiovascular system. Circ Res 116:531–549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Canton M, Menazza S, Sheeran FL, Polverino de Laureto P, Di Lisa F, Pepe S (2011) Oxidation of myofibrillar proteins in human heart failure. J Am Coll Cardiol 57:300–309

    Article  CAS  PubMed  Google Scholar 

  • Cantu-Medellin N, Kelley EE (2013) Xanthine oxidoreductase-catalyzed reactive species generation: a process in critical need of reevaluation. Redox Biol 1:353–358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen YR, Zweier JL (2014) Cardiac mitochondria and reactive oxygen species generation. Circ Res 114:524–537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cosentino F, Francia P, Camici GG, Pelicci PG, Lüscher TF, Volpe M (2008) Final common molecular pathways of aging and cardiovascular disease: role of the p66Shc protein. Arterioscler Thromb Vasc Biol 28:622–628

    Article  CAS  PubMed  Google Scholar 

  • Cox AG, Winterbourn CC, Hampton MB (2010) Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling. Biochem J 425:313–325

    Article  CAS  Google Scholar 

  • Dai DF, Rabinovitch PS (2009) Cardiac aging in mice and humans: the role of mitochondrial oxidative stress. Trends Cardiovasc Med 19:213–220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dai DF, Johnson SC, Villarin JJ, Chin MT, Nieves-Cintron M, Chen T, Marcinek DJ, Dorn GW 2nd, Kang YJ, Prolla TA, Santana LF, Rabinovitch PS (2011) Mitochondrial oxidative stress mediates angiotensin ii-induced cardiac hypertrophy and galphaq overexpression-induced heart failure. Circ Res 108:837–846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Di Lisa F, Kaludercic N, Carpi A, Menabò R, Giorgio M (2009) Mitochondria and vascular pathology. Pharmacol Rep 61:123–130

    Article  PubMed  Google Scholar 

  • Di Lisa F, Canton M, Carpi A, Kaludercic N, Menabò R, Menazza S, Semenzato M (2011) Mitochondrial injury and protection in ischemic pre- and postconditioning. Antioxid Redox Signal 14:881–891

    Article  PubMed  Google Scholar 

  • Ferdinandy P, Hausenloy DJ, Heusch G, Baxter GF, Schulz R (2014) Interaction of risk factors, comorbidities, and comedications with ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning. Pharmacol Rev 66:1142–1174

    Article  CAS  PubMed  Google Scholar 

  • Forman HJ, Ursini F, Maiorino M (2014) An overview of mechanisms of redox signaling. J Mol Cell Cardiol 73:2–9

    Article  CAS  PubMed  Google Scholar 

  • Giorgio M, Migliaccio E, Orsini F, Paolucci D, Moroni M, Contursi C, Pelliccia G, Luzi L, Minucci S, Marcaccio M, Pinton P, Rizzuto R, Bernardi P, Paolucci F, Pelicci PG (2005) Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis. Cell 122:221–233

    Article  CAS  PubMed  Google Scholar 

  • Granger DN, Kvietys PR (2015) Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol 6:524–551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Hayes JD, Dinkova-Kostova AT (2014) The nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci 39:199–218

    Article  CAS  PubMed  Google Scholar 

  • Hirschhäuser C, Bornbaum J, Reis A, Böhme S, Kaludercic N, Menabò R, Di Lisa F, Boengler K, Shah AM, Schulz R, Schmidt HH (2015) NOX4 in mitochondria: yeast two-hybrid-based interaction with complex I without relevance for basal reactive oxygen species? Antioxid Redox Signal 23(14):1106–1112

    Article  PubMed  PubMed Central  Google Scholar 

  • Kaludercic N, Mialet-Perez J, Paolocci N, Parini A, Di Lisa F (2014a) Monoamine oxidases as sources of oxidants in the heart. J Mol Cell Cardiol 73:34–42

    Article  CAS  PubMed  Google Scholar 

  • Kaludercic N, Deshwal S, Di Lisa F (2014b) Reactive oxygen species and redox compartmentalization. Front Physiol 5:285

    Article  PubMed  PubMed Central  Google Scholar 

  • Kirca M, Kleinbongard P, Soetkamp D, Heger J, Csonka C, Ferdinandy P, Schulz R (2015) Interaction between connexin 43 and nitric oxide synthase in mice heart mitochondria. J Cell Mol Med 19:815–825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Korshunov SS, Skulachev VP, Starkov AA (1997) High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett 416:15–18

    Article  CAS  PubMed  Google Scholar 

  • Kumar V, Kitaeff N, Hampton MB, Cannell MB, Winterbourn CC (2009) Reversible oxidation of mitochondrial peroxiredoxin 3 in mouse heart subjected to ischemia and reperfusion. FEBS Lett 583:997–1000

    Article  CAS  PubMed  Google Scholar 

  • Luo S, Lei H, Qin H, Xia Y (2014) Molecular mechanisms of endothelial NO synthase uncoupling. Curr Pharm Des 20:3548–3553

    Article  CAS  PubMed  Google Scholar 

  • Matsushima S, Ide T, Yamato M, Matsusaka H, Hattori F, Ikeuchi M, Kubota T, Sunagawa K, Hasegawa Y, Kurihara T, Oikawa S, Kinugawa S, Tsutsui H (2006) Overexpression of mitochondrial peroxiredoxin-3 prevents left ventricular remodeling and failure after myocardial infarction in mice. Circulation 113:1779–1786

    Article  CAS  PubMed  Google Scholar 

  • Matsushima S, Tsutsui H, Sadoshima J (2014) Physiological and pathological functions of NADPH oxidases during myocardial ischemia-reperfusion. Trends Cardiovasc Med 24:202–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Milsom AB, Fernandez BO, Garcia-Saura MF, Rodriguez J, Feelisch M (2012) Contributions of nitric oxide synthases, dietary nitrite/nitrate, and other sources to the formation of NO signaling products. Antioxid Redox Signal 17:422–432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murphy E, Kohr M, Menazza S, Nguyen T, Evangelista A, Sun J, Steenbergen C (2014) Signaling by S-nitrosylation in the heart. J Mol Cell Cardiol 73:18–25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13

    Article  CAS  PubMed  Google Scholar 

  • Murphy MP (2012) Mitochondrial thiols in antioxidant protection and redox signaling: distinct roles for glutathionylation and other thiol modifications. Antioxid Redox Signal 16:476–495

    Article  CAS  PubMed  Google Scholar 

  • Nickel A, Kohlhaas M, Maack C (2014) Mitochondrial reactive oxygen species production and elimination. J Mol Cell Cardiol 73:26–33

    Article  CAS  PubMed  Google Scholar 

  • Orsini F, Moroni M, Contursi C, Pelicci PG, Giorgio M, Migliaccio E (2006) Mitochondrial regulation of p66Shc mitochondrial function. Biol Chem 387:1405–1410

    Article  CAS  PubMed  Google Scholar 

  • Rassaf T, Ferdinandy P, Schulz R (2014) Nitrite in organ protection. Br J Pharmacol 171:1–11

    Article  CAS  PubMed  Google Scholar 

  • Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308:1909–1911

    Article  CAS  PubMed  Google Scholar 

  • Schulz R, Ferdinandy P (2013) Does nitric oxide signaling differ in pre- and post-conditioning? Importance of S-nitrosylation vs. protein kinase G activation. Free Radic Biol Med 54:113–115

    Article  CAS  PubMed  Google Scholar 

  • Schulz R, Görge PM, Görbe A, Ferdinandy P, Lampe PD, Leybaert L (2015) Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection. Pharmacol Ther 153:90–106

    CAS  PubMed  Google Scholar 

  • Semenza GL (2014) Hypoxia-inducible factor 1 and cardiovascular disease. Annual Rev Physiol 76:39–56

    Article  CAS  PubMed  Google Scholar 

  • Sies H (2014) Role of metabolic H2O2 generation: redox signaling and oxidative stress. J Biol Chem 289:8735–8741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soetkamp D, Nguyen TT, Menazza S, Hirschhäuser C, Hendgen-Cotta UB, Rassaf T, Schlüter KD, Boengler K, Murphy E, Schulz R (2014) S-nitrosation of mitochondrial connexin 43 regulates mitochondrial function. Basic Res Cardiol 109:433

    Article  PubMed  PubMed Central  Google Scholar 

  • Trinei M, Migliaccio E, Bernardi P, Paolucci F, Pelicci P, Giorgio M (2013) Mitochondria, and the generation of reactive oxygen species. p66Shc. Methods Enzymol 528:99–110

    Article  CAS  PubMed  Google Scholar 

  • Vanden Hoek TL, Li C, Shao Z, Schumacker PT, Becker LB (1997) Significant levels of oxidants are generated by isolated cardiomyocytes during ischemia prior to reperfusion. J Mol Cell Cardiol 29:2571–2583

    Article  CAS  PubMed  Google Scholar 

  • Victorino VJ, Mencalha AL, Panis C (2015) Post-translational modifications disclose a dual role for redox stress in cardiovascular pathophysiology. Life Sci 129:42–47

    Article  CAS  PubMed  Google Scholar 

  • Yun J, Finkel T (2014) Mitohormesis. Cell Metab 19:757–766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang YS, Liu B, Luo XJ, Zhang JJ, Li NS, Ma QL, Jiang JL, Li YJ, Li Q, Peng J (2015) A novel function of nuclear nonmuscle myosin regulatory light chain in promotion of xanthine oxidase transcription after myocardial ischemia/reperfusion. Free Radic Biol Med 83:115–128

    Article  CAS  PubMed  Google Scholar 

  • Zorov DB, Juhaszova M, Sollott SJ (2014) Mitochondrial reactive oxygen species (ros) and ros-induced ros release. Physiol Rev 94:909–950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zweier JL (1988) Measurement of superoxide-derived free radicals in the reperfused heart. Evidence for a free radical mechanism of reperfusion injury. J Biol Chem 263:1353–1357

    CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Institute of Physiology, Justus-Liebig-Universität Gießen, Giessen, Germany

    Rainer Schulz

  2. Department of Biomedical Sciences, University of Padova, Padova, Italy

    Fabio Di Lisa

Authors
  1. Rainer Schulz
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  2. Fabio Di Lisa
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Correspondence to Rainer Schulz .

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Editors and Affiliations

  1. Institute of Physiology, Justus-Liebig-Universität Giessen, Giessen, Hessen, Germany

    Klaus-Dieter Schlüter

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Schulz, R., Di Lisa, F. (2016). Oxidative Stress and Nitrosative Stress. In: Schlüter, KD. (eds) Cardiomyocytes – Active Players in Cardiac Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-31251-4_10

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