Skip to main content
SpringerLink
Log in

Mitochondrial pathways for ROS formation and myocardial injury: the relevance of p66Shc and monoamine oxidase

  • Review
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Abstract

Although mitochondria are considered the most relevant site for the formation of reactive oxygen species (ROS) in cardiac myocytes, a major and unsolved issue is where ROS are generated in mitochondria. Respiratory chain is generally indicated as a main site for ROS formation. However, other mitochondrial components are likely to contribute to ROS generation. Recent reports highlight the relevance of monoamine oxidases (MAO) and p66Shc. The importance of these systems in the irreversibility of ischemic heart injury will be discussed along with the cardioprotective effects elicited by both MAO inhibition and p66Shc knockout. Finally, recent evidence will be reviewed that highlight the relevance of mitochondrial ROS formation also in myocardial failure and atherosclerosis.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Andoh T, Lee SY, Chiueh CC (2000) Preconditioning regulation of bcl-2 and p66Shc by human NOS1 enhances tolerance to oxidative stress. FASEB J 14:2144–2146

    PubMed  CAS  Google Scholar 

  2. Asimakis GK, Lick S, Patterson C (2002) Postischemic recovery of contractile function is impaired in SOD2(+/–) but not SOD1(+/–) mouse hearts. Circulation 105:981–986

    Article  PubMed  CAS  Google Scholar 

  3. Aulak KS, Miyagi M, Yan L, West KA, Massillon D, Crabb JW, Stuehr DJ (2001) Proteomic method identifies proteins nitrated in vivo during inflammatory challenge. Proc Natl Acad Sci USA 98:12056–12061

    Article  PubMed  CAS  Google Scholar 

  4. Baines CP (2009) The mitochondrial permeability transition pore and ischemia-reperfusion injury. Basic Res Cardiol (in press)

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

    Article  PubMed  CAS  Google Scholar 

  6. Bauersachs J, Widder JD (2008) Endothelial dysfunction in heart failure. Pharmacol Rep 60:119–126

    PubMed  CAS  Google Scholar 

  7. Beckman JS, Koppenol WH (1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 271:C1424–C1437

    PubMed  CAS  Google Scholar 

  8. Beltran B, Mathur A, Duchen MR, Erusalimsky JD, Moncada S (2000) The effect of nitric oxide on cell respiration: a key to understanding its role in cell survival or death. Proc Natl Acad Sci USA 97:14602–14607

    Article  PubMed  CAS  Google Scholar 

  9. Bernardi P, Petronilli V, Di Lisa F, Forte M (2001) A mitochondrial perspective on cell death. Trends Biochem Sci 26:112–117

    Article  PubMed  CAS  Google Scholar 

  10. Bernardi P, Krauskopf A, Basso E, Petronilli V, Blalchy-Dyson E, Di Lisa F, Forte MA (2006) The mitochondrial permeability transition from in vitro artifact to disease target. FEBS J 273:2077–2099

    Article  PubMed  CAS  Google Scholar 

  11. 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  PubMed  CAS  Google Scholar 

  12. Berniakovich I, Trinei M, Stendardo M, Migliaccio E, Minucci S, Bernardi P, Pelicci PG, Giorgio M (2008) p66Shc-Generated oxidative signal promotes fat accumulation. J Biol Chem 283:34283–34293

    Article  PubMed  CAS  Google Scholar 

  13. Bianchi P, Kunduzova O, Masini E, Cambon C, Bani D, Raimondi L, Seguelas MH, Nistri S, Colucci W, Leducq N, Parini A (2005) Oxidative stress by monoamine oxidase mediates receptor-independent cardiomyocyte apoptosis by serotonin and postischemic myocardial injury. Circulation 112:3297–3305

    Article  PubMed  CAS  Google Scholar 

  14. Bianchi P, Pimentel DR, Murphy MP, Colucci WS, Parini A (2005) A new hypertrophic mechanism of serotonin in cardiac myocytes: receptor-independent ROS generation. FASEB J 19:641–643

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  16. Booz GW (2005) Growing old, angiotensin II, cardiac hypertrophy, and death: making the connection with p66Shc. Hypertension 46:259–260

    Article  PubMed  CAS  Google Scholar 

  17. Brennan JP, Bardswell SC, Burgoyne JR, Fuller W, Schroder E, Wait R, Begum S, Kentish JC, Eaton P (2006) Oxidant-induced activation of type I protein kinase A is mediated by RI subunit interprotein disulfide bond formation. J Biol Chem 281:21827–21836

    Article  PubMed  CAS  Google Scholar 

  18. Brown GC, Cooper CE (1994) Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett 356:295–298

    Article  PubMed  CAS  Google Scholar 

  19. Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA (1993) Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science 262:578–580

    Article  PubMed  CAS  Google Scholar 

  20. Burgoyne JR, Madhani M, Cuello F, Charles RL, Brennan JP, Schroder E, Browning DD, Eaton P (2007) Cysteine redox sensor in PKGIa enables oxidant-induced activation. Science 317:1393–1397

    Article  PubMed  CAS  Google Scholar 

  21. Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29:222–230

    Article  PubMed  CAS  Google Scholar 

  22. Canton M, Neverova I, Menabò R, Van Eyk JE, Di Lisa F (2004) Evidence of myofibrillar protein oxidation induced by postischemic reperfusion in isolated rat hearts. Am J Physiol Heart Circ Physiol 286:H870–H877

    Article  PubMed  CAS  Google Scholar 

  23. Cases O, Seif I, Grimsby J, Gaspar P, Chen K, Pournin S, Muller U, Aguet M, Babinet C, Shih JC (1995) Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAO-A. Science 268:1763–1766

    Article  PubMed  CAS  Google Scholar 

  24. Cesselli D, Jakoniuk I, Barlucchi L, Beltrami AP, Hintze TH, Nadal-Ginard B, Kajstura J, Leri A, Anversa P (2001) Oxidative stress-mediated cardiac cell death is a major determinant of ventricular dysfunction and failure in dog dilated cardiomyopathy. Circ Res 89:279–286

    Article  PubMed  CAS  Google Scholar 

  25. Chen Z, Siu B, Ho YS, Vincent R, Chua CC, Hamdy RC, Chua BH (1998) Overexpression of MnSOD protects against myocardial ischemia/reperfusion injury in transgenic mice. J Mol Cell Cardiol 30:2281–2289

    Article  PubMed  CAS  Google Scholar 

  26. Chen CH, Budas GR, Churchill EN, Disatnik MH, Hurley TD, Mochly-Rosen D (2008) Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. Science 321:1493–1495

    Article  PubMed  CAS  Google Scholar 

  27. Clarke SJ, Khaliulin I, Das M, Parker JE, Heesom KJ, Halestrap AP (2008) Inhibition of mitochondrial permeability transition pore opening by ischemic preconditioning is probably mediated by reduction of oxidative stress rather than mitochondrial protein phosphorylation. Circ Res 102:1082–1090

    Article  PubMed  CAS  Google Scholar 

  28. Cleeter MW, Cooper JM, rley-Usmar VM, Moncada S, Schapira AH (1994) Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide. Implications for neurodegenerative diseases. FEBS Lett 345:50–54

    Article  PubMed  CAS  Google Scholar 

  29. Coatrieux C, Sanson M, Negre-Salvayre A, Parini A, Hannun Y, Itohara S, Salvayre R, Auge N (2007) MAO-A-induced mitogenic signaling is mediated by reactive oxygen species, MMP-2, and the sphingolipid pathway. Free Radic Biol Med 43:80–89

    Article  PubMed  CAS  Google Scholar 

  30. Cosentino F, Francia P, Camici GG, Pelicci PG, Luscher 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  PubMed  CAS  Google Scholar 

  31. Costa AD, Quinlan CL, Andrukhiv A, West IC, Jaburek M, Garlid KD (2006) The direct physiological effects of mitoK(ATP) opening on heart mitochondria. Am J Physiol Heart Circ Physiol 290:H406–H415

    Article  PubMed  CAS  Google Scholar 

  32. Costantini P, Chernyak BV, Petronilli V, Bernardi P (1995) Selective inhibition of the mitochondrial permeability transition pore at the oxidation-reduction sensitive dithiol by monobromobimane. FEBS Lett 362:239–242

    Article  PubMed  CAS  Google Scholar 

  33. Costantini P, Chernyak BV, Petronilli V, Bernardi P (1996) Modulation of the mitochondrial permeability transition pore by pyridine nucleotides and dithiol oxidation at two separate sites. J Biol Chem 271:6746–6751

    Article  PubMed  CAS  Google Scholar 

  34. Daiber A, Wenzel P, Oelze M, Schuhmacher S, Jansen T, Munzel T (2008) Mitochondrial aldehyde dehydrogenase (ALDH-2)-Maker of and marker for nitrate tolerance in response to nitroglycerin treatment. Chem Biol Interact (in press)

  35. Davidson SM, Duchen MR (2007) Endothelial mitochondria: contributing to vascular function and disease. Circ Res 100:1128–1141

    Article  PubMed  CAS  Google Scholar 

  36. Di Lisa F, Bernardi P (2005) Mitochondrial function and myocardial aging. A critical analysis of the role of permeability transition. Cardiovasc Res 66:222–232

    Article  PubMed  CAS  Google Scholar 

  37. Di Lisa F, Menabò R, Canton M, Petronilli V (1998) The role of mitochondria in the salvage and the injury of the ischemic myocardium. Biochim Biophys Acta 1366:69–78

    Article  PubMed  CAS  Google Scholar 

  38. Di Lisa F, Canton M, Menabò R, Dodoni G, Bernardi P (2003) Mitochondria and reperfusion injury. The role of permeability transition. Basic Res Cardiol 98:235–241

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  40. Dworakowski R, Alom-Ruiz SP, Shah AM (2008) NADPH oxidase-derived reactive oxygen species in the regulation of endothelial phenotype. Pharmacol Rep 60:21–28

    PubMed  CAS  Google Scholar 

  41. Edmondson DE, Binda C, Mattevi A (2004) The FAD binding sites of human monoamine oxidases A and B. Neurotoxicology 25:63–72

    Article  PubMed  CAS  Google Scholar 

  42. Edmondson DE, Mattevi A, Binda C, Li M, Hubalek F (2004) Structure and mechanism of monoamine oxidase. Curr Med Chem 11:1983–1993

    PubMed  CAS  Google Scholar 

  43. Erickson JR, Joiner ML, Guan X, Kutschke W, Yang J, Oddis CV, Bartlett RK, Lowe JS, O’Donnell SE, ykin-Burns N, Zimmerman MC, Zimmerman K, Ham AJ, Weiss RM, Spitz DR, Shea MA, Colbran RJ, Mohler PJ, Anderson ME (2008) A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell 133:462–474

    Article  PubMed  CAS  Google Scholar 

  44. Ferdinandy P, Schulz R, Baxter GF (2007) Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning, and postconditioning. Pharmacol Rev 59:418–458

    Article  PubMed  CAS  Google Scholar 

  45. Finetti F, Pellegrini M, Ulivieri C, Savino MT, Paccagnini E, Ginanneschi C, Lanfrancone L, Pelicci PG, Baldari CT (2008) The proapoptotic and antimitogenic protein p66Shc acts as a negative regulator of lymphocyte activation and autoimmunity. Blood 111:5017–5027

    Article  PubMed  CAS  Google Scholar 

  46. Finkel T (2000) Redox-dependent signal transduction. FEBS Lett 476:52–54

    Article  PubMed  CAS  Google Scholar 

  47. Fiorina P, Corradi D, Pinelli S, Maestri R, Lagrasta C, Buscaglia M, Davalli A, Folli F, Astorri E (2004) Apoptotic/mytogenic pathways during human heart development. Int J Cardiol 96:409–417

    Article  PubMed  Google Scholar 

  48. Flohe L, Ursini F (2008) Peroxidase: a term of many meanings. Antioxid Redox Signal 10:1485–1490

    Article  PubMed  CAS  Google Scholar 

  49. Fridovich I (1995) Superoxide radical and superoxide dismutases. Annu Rev Biochem 64:97–112

    Article  PubMed  CAS  Google Scholar 

  50. Giordano FJ (2005) Oxygen, oxidative stress, hypoxia and heart failure. J Clin Invest 115:500–508

    PubMed  CAS  Google Scholar 

  51. 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  PubMed  CAS  Google Scholar 

  52. Giorgio M, Trinei M, Migliaccio E, Pelicci PG (2007) Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? Nat Rev Mol Cell Biol 8:722–728

    Article  PubMed  CAS  Google Scholar 

  53. Glab M, Lojek A, Wrzosek A, Dolowy K, Szewczyk A (2006) Endothelial mitochondria as a possible target for potassium channel modulators. Pharmacol Rep 58(Suppl):89–95

    PubMed  Google Scholar 

  54. Gordon LI, Burke MA, Singh AT, Prachand S, Lieberman ED, Sun L, Naik TJ, Naga Prasad SV, Ardehali H (2008) Blockade of the erbB2 receptor induces cardiomyocyte death through mitochondrial- and reactive oxygen species-dependent pathways. J Biol Chem (in press)

  55. Graiani G, Lagrasta C, Migliaccio E, Spillmann F, Meloni M, Madeddu P, Quaini F, Padura IM, Lanfrancone L, Pelicci P, Emanueli C (2005) Genetic deletion of the p66Shc adaptor protein protects from angiotensin II-induced myocardial damage. Hypertension 46:433–440

    Article  PubMed  CAS  Google Scholar 

  56. Gutierrez J, Ballinger SW, Darley-Usmar VM, Landar A (2006) Free radicals, mitochondria, and oxidized lipids: the emerging role in signal transduction in vascular cells. Circ Res 99:924–932

    Article  PubMed  CAS  Google Scholar 

  57. Haynes V, Elfering SL, Squires RJ, Traaseth N, Solien J, Ettl A, Giulivi C (2003) Mitochondrial nitric-oxide synthase: role in pathophysiology. IUBMB Life 55:599–603

    Article  PubMed  CAS  Google Scholar 

  58. Hengartner MO (2000) The biochemistry of apoptosis. Nature 407:770–776

    Article  PubMed  CAS  Google Scholar 

  59. Ide T, Tsutsui H, Kinugawa S, Suematsu N, Hayashidani S, Ichikawa K, Utsumi H, Machida Y, Egashira K, Takeshita A (2000) Direct evidence for increased hydroxyl radicals originating from superoxide in the failing myocardium. Circ Res 86:152–157

    PubMed  CAS  Google Scholar 

  60. Janssen-Heininger YM, Mossman BT, Heintz NH, Forman HJ, Kalyanaraman B, Finkel T, Stamler JS, Rhee SG, van d, V (2008) Redox-based regulation of signal transduction: principles, pitfalls, and promises. Free Radic Biol Med 45:1–17

  61. Kaludercic N, Feng N, Nagayama T, Bedja D, Carpi A, Vecoli C, Cormaci G, Gabrielson K, Kass D, Paolocci N, Di Lisa F (2007) Monoamine oxidase A is upregulated in cardiac hypertrophy and is a major determinant of the transition from compensation to failure. Circ Res 101(11):7 (abstract)

    Google Scholar 

  62. Lemasters JJ, Qian T, Bradham CA, Brenner DA, Cascio WE, Trost LC, Nishimura Y, Nieminen AL, Herman B (1999) Mitochondrial dysfunction in the pathogenesis of necrotic and apoptotic cell death. J Bioenerg Biomembr 31:305–319

    Article  PubMed  CAS  Google Scholar 

  63. Lenders JW, Eisenhofer G, Abeling NG, Berger W, Murphy DL, Konings CH, Wagemakers LM, Kopin IJ, Karoum F, van Gennip AH, Brunner HG (1996) Specific genetic deficiencies of the A and B isoenzymes of monoamine oxidase are characterized by distinct neurochemical and clinical phenotypes. J Clin Invest 97:1010–1019

    Article  PubMed  CAS  Google Scholar 

  64. Levitt P, Pintar JE, Breakefield XO (1982) Immunocytochemical demonstration of monoamine oxidase B in brain astrocytes and serotonergic neurons. Proc Natl Acad Sci USA 79:6385–6389

    Article  PubMed  CAS  Google Scholar 

  65. Liu Y, Yang XM, Iliodromitis EK, Kremastinos DT, Dost T, Cohen MV, Downey JM (2008) Redox signaling at reperfusion is required for protection from ischemic preconditioning but not from a direct PKC activator. Basic Res Cardiol 103:54–59

    Article  PubMed  CAS  Google Scholar 

  66. Madamanchi NR, Runge MS (2007) Mitochondrial dysfunction in atherosclerosis. Circ Res 100:460–473

    Article  PubMed  CAS  Google Scholar 

  67. Maurel A, Hernandez C, Kunduzova O, Bompart G, Cambon C, Parini A, Frances B (2003) Age-dependent increase in hydrogen peroxide production by cardiac monoamine oxidase A in rats. Am J Physiol Heart Circ Physiol 284:H1460–H1467

    PubMed  CAS  Google Scholar 

  68. Melov S, Coskun PE, Wallace DC (1999) Mouse models of mitochondrial disease, oxidative stress, and senescence. Mutat Res 434:233–242

    PubMed  CAS  Google Scholar 

  69. Menini S, Amadio L, Oddi G, Ricci C, Pesce C, Pugliese F, Giorgio M, Migliaccio E, Pelicci P, Iacobini C, Pugliese G (2006) Deletion of p66Shc longevity gene protects against experimental diabetic glomerulopathy by preventing diabetes-induced oxidative stress. Diabetes 55:1642–1650

    Article  PubMed  CAS  Google Scholar 

  70. Migliaccio E, Giorgio M, Mele S, Pelicci G, Reboldi P, Pandolfi PP, Lanfrancone L, Pelicci PG (1999) The p66Shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402:309–313

    Article  PubMed  CAS  Google Scholar 

  71. Migliaccio E, Giorgio M, Pelicci PG (2006) Apoptosis and aging: role of p66Shc redox protein. Antioxid Redox Signal 8:600–608

    Article  PubMed  CAS  Google Scholar 

  72. Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J (in press)

  73. Murphy E, Steenbergen C (2008) Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol Rev 88:581–609

    Article  PubMed  CAS  Google Scholar 

  74. Napoli C, Martin-Padura I, de Nigris F, Giorgio M, Mansueto G, Somma P, Condorelli M, Sica G, De Rosa G, Pelicci P (2003) Deletion of the p66Shc longevity gene reduces systemic and tissue oxidative stress, vascular cell apoptosis, and early atherogenesis in mice fed a high-fat diet. Proc Natl Acad Sci USA 100:2112–2116

    Article  PubMed  CAS  Google Scholar 

  75. Nemoto S, Finkel T (2002) Redox regulation of forkhead proteins through a p66Shc-dependent signaling pathway. Science 295:2450–2452

    Article  PubMed  CAS  Google Scholar 

  76. Newmeyer DD, Ferguson-Miller S (2003) Mitochondria: releasing power for life and unleashing the machineries of death. Cell 112:481–490

    Article  PubMed  CAS  Google Scholar 

  77. Ohashi M, Runge MS, Faraci FM, Heistad DD (2006) MnSOD deficiency increases endothelial dysfunction in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 26:2331–2336

    Article  PubMed  CAS  Google Scholar 

  78. Okado-Matsumoto A, Fridovich I (2001) Subcellular distribution of superoxide dismutases (SOD) in rat liver: Cu, Zn-SOD in mitochondria. J Biol Chem 276:38388–38393

    Article  PubMed  CAS  Google Scholar 

  79. Orsini F, Migliaccio E, Moroni M, Contursi C, Raker VA, Piccini D, Martin-Padura I, Pelliccia G, Trinei M, Bono M, Puri C, Tacchetti C, Ferrini M, Mannucci R, Nicoletti I, Lanfrancone L, Giorgio M, Pelicci PG (2004) The life span determinant p66Shc localizes to mitochondria where it associates with mitochondrial heat shock protein 70 and regulates trans-membrane potential. J Biol Chem 279:25689–25695

    Article  PubMed  CAS  Google Scholar 

  80. Papa S, Skulachev VP (1997) Reactive oxygen species, mitochondria, apoptosis and aging. Mol Cell Biochem 174:305–319

    Article  PubMed  CAS  Google Scholar 

  81. Pchejetski D, Kunduzova O, Dayon A, Calise D, Seguelas MH, Leducq N, Seif I, Parini A, Cuvillier O (2007) Oxidative stress-dependent sphingosine kinase-1 inhibition mediates monoamine oxidase A-associated cardiac cell apoptosis. Circ Res 100:41–49

    Article  PubMed  CAS  Google Scholar 

  82. Pelicci G, Lanfrancone L, Grignani F, McGlade J, Cavallo F, Forni G, Nicoletti I, Grignani F, Pawson T, Pelicci PG (1992) A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction. Cell 70:93–104

    Article  PubMed  CAS  Google Scholar 

  83. Pellegrini M, Pacini S, Baldari CT (2005) p66Shc: the apoptotic side of Shc proteins. Apoptosis 10:13–18

    Article  PubMed  CAS  Google Scholar 

  84. Pinton P, Rimessi A, Marchi S, Orsini F, Migliaccio E, Giorgio M, Contursi C, Minucci S, Mantovani F, Wieckowski MR, Del SG, Pelicci PG, Rizzuto R (2007) Protein kinase C beta and prolyl isomerase 1 regulate mitochondrial effects of the life-span determinant p66Shc. Science 315:659–663

    Article  PubMed  CAS  Google Scholar 

  85. Pletscher A (1991) The discovery of antidepressants: a winding path. Experientia 47:4–8

    Article  PubMed  CAS  Google Scholar 

  86. Poderoso JJ, Carreras MC, Lisdero C, Riobo N, Schopfer F, Boveris A (1996) Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Arch Biochem Biophys 328:85–92

    Article  PubMed  CAS  Google Scholar 

  87. Purdom S, Chen QM (2003) p66(Shc): at the crossroad of oxidative stress and the genetics of aging. Trends Mol Med 9:206–210

    Article  PubMed  CAS  Google Scholar 

  88. Riederer P, Lachenmayer L, Laux G (2004) Clinical applications of MAO-inhibitors. Curr Med Chem 11:2033–2043

    PubMed  CAS  Google Scholar 

  89. Rota M, LeCapitaine N, Hosoda T, Boni A, De AA, Padin-Iruegas ME, Esposito G, Vitale S, Urbanek K, Casarsa C, Giorgio M, Luscher TF, Pelicci PG, Anversa P, Leri A, Kajstura J (2006) Diabetes promotes cardiac stem cell aging and heart failure, which are prevented by deletion of the p66Shc gene. Circ Res 99:42–52

    Article  PubMed  CAS  Google Scholar 

  90. Salet C, Moreno G, Ricchelli F, Bernardi P (1997) Singlet oxygen produced by photodynamic action causes inactivation of the mitochondrial permeability transition pore. J Biol Chem 272:21938–21943

    Article  PubMed  CAS  Google Scholar 

  91. Sarkela TM, Berthiaume J, Elfering S, Gybina AA, Giulivi C (2001) The modulation of oxygen radical production by nitric oxide in mitochondria. J Biol Chem 276:6945–6949

    Article  PubMed  CAS  Google Scholar 

  92. Shih JC (2004) Cloning, after cloning, knock-out mice, and physiological functions of MAO A and B. Neurotoxicology 25:21–30

    Article  PubMed  CAS  Google Scholar 

  93. Siddall HK, Warrell CE, Yellon DM, Mocanu MM (2008) Ischemia-reperfusion injury and cardioprotection: investigating PTEN, the phosphatase that negatively regulates PI3 K, using a congenital model of PTEN haploinsufficiency. Basic Res Cardiol 103:560–568

    Article  PubMed  CAS  Google Scholar 

  94. Sivasubramaniam SD, Finch CC, Rodriguez MJ, Mahy N, Billett EE (2003) A comparative study of the expression of monoamine oxidase-A and -B mRNA and protein in non-CNS human tissues. Cell Tissue Res 313:291–300

    Article  PubMed  CAS  Google Scholar 

  95. Tipton KF, Boyce S, O’Sullivan J, Davey GP, Healy J (2004) Monoamine oxidases: certainties and uncertainties. Curr Med Chem 11:1965–1982

    PubMed  CAS  Google Scholar 

  96. Trinei M, Giorgio M, Cicalese A, Barozzi S, Ventura A, Migliaccio E, Milia E, Padura IM, Raker VA, Maccarana M, Petronilli V, Minucci S, Bernardi P, Lanfrancone L, Pelicci PG (2002) A p53–p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis. Oncogene 21:3872–3878

    Article  PubMed  CAS  Google Scholar 

  97. Turrens JF (2003) Mitochondrial formation of reactive oxygen species. J Physiol 552:335–344

    Article  PubMed  CAS  Google Scholar 

  98. Wenzel P, Muller J, Zurmeyer S, Schuhmacher S, Schulz E, Oelze M, Pautz A, Kawamoto T, Wojnowski L, Kleinert H, Munzel T, Daiber A (2008) ALDH-2 deficiency increases cardiovascular oxidative stress–evidence for indirect antioxidative properties. Biochem Biophys Res Commun 367:137–143

    Article  PubMed  CAS  Google Scholar 

  99. Youdim MB, Edmondson D, Tipton KF (2006) The therapeutic potential of monoamine oxidase inhibitors. Nat Rev Neurosci 7:295–309

    Article  PubMed  CAS  Google Scholar 

  100. Zaccagnini G, Martelli F, Fasanaro P, Magenta A, Gaetano C, Di Carlo A, Biglioli P, Giorgio M, Martin-Padura I, Pelicci PG, Capogrossi MC (2004) p66ShcA modulates tissue response to hindlimb ischemia. Circulation 109:2917–2923

    Article  PubMed  Google Scholar 

  101. Zhao W, Fan GC, Zhang ZG, Bandyopadhyay A, Zhou X, Kranias EG (2008) Protection of peroxiredoxin II on oxidative stress-induced cardiomyocyte death and apoptosis. Basic Res Cardiol (in press)

Download references

Acknowledgments

This work has been supported by University of Padova (Post-Doctoral Fellowship to NK), MIUR and CNR.

Author information

Authors and Affiliations

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

    Fabio Di Lisa, Nina Kaludercic & Andrea Carpi

  2. Institute for Neuroscience, CNR, Padova, Italy

    Fabio Di Lisa & Roberta Menabò

  3. Dip. di Scienze Biomediche Sperimentali, Viale G. Colombo, 3, 35121, Padova, Italy

    Fabio Di Lisa

  4. European Institute of Oncology, Milan, Italy

    Marco Giorgio

Authors
  1. Fabio Di Lisa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nina Kaludercic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrea Carpi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Roberta Menabò
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marco Giorgio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fabio Di Lisa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Di Lisa, F., Kaludercic, N., Carpi, A. et al. Mitochondrial pathways for ROS formation and myocardial injury: the relevance of p66Shc and monoamine oxidase. Basic Res Cardiol 104, 131–139 (2009). https://doi.org/10.1007/s00395-009-0008-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00395-009-0008-4

Keywords

Search

Navigation