Myocardial Ischemia-reperfusion Injury: Role of the Peroxynitrite-poly(ADP-ribose) Polymerase Pathway

  • C. Szabó
  • L. Liaudet

Abstract

The enzyme poly (ADP-ribose) polymerase (PARP) — also termed poly (ADP-ribose) synthetase (PARS) and poly (ADP-ribose) transferase (pPADPRT) — is an abundant nuclear protein present throughout the phylogenetic spectrum. The precise physiologic roles of PARP remain undefined; its traditional role as a DNA-repair enzyme has been questioned by recent studies. PARP plays diverse roles, participating in DNA repair, chromatin relaxation, cell differentiation, DNA replication, transcriptional regulation, control of cell cycle, p53 expression and apoptosis, and transformation [1].

Keywords

Neutrophil Infiltration PARP Inhibitor PARP Cleavage PARP Activation Myocardial Reperfusion Injury 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    De Murcia G, Shall S (2000) From DNA Damage and Stress Signaling to Cell Death; Poly ADP-ribosylation Reactions. Oxford University Press, OxfordGoogle Scholar
  2. 2.
    Szabo C (2000) Cell Death: The Role of PARP. CRC Press, Boca RatonCrossRefGoogle Scholar
  3. 3.
    Szabó C, Dawson VL (1998) Role of poly(ADP-ribose) synthetase in inflammation and ischaemia-reperfusion. Trends Pharmacol Sci 19: 287–298PubMedCrossRefGoogle Scholar
  4. 4.
    Liaudet L, Szabó E, Timashpolsky L, Virâg L, Cziraki A, Szabó C (2001) Localization of poly (ADP-ribose) polymerase (PARP) activation in a rat model of myocardial reperfusion injury: suppression of PARP activation and long-term morphological and functional improvement by 3-aminobenzamide. Br J Pharmacol 133: 1424–1430PubMedCrossRefGoogle Scholar
  5. 5.
    Pieper AA, Walles T, Wei G, Clements EE, Verma A, Snyder SH (2000) Myocardial postischemic injury is reduced by polyADPribose polymerase-1 gene disruption. Mol Med 6: 271–282PubMedGoogle Scholar
  6. 6.
    Szabados E, Literati-Nagy P, Farkas B, Sumegi B (2000) BGP-15, a nicotinic amidoxime derivate protecting heart from ischemia reperfusion injury through modulation of poly(ADPribose) polymerase. Biochem Pharmacol 59: 937–945PubMedCrossRefGoogle Scholar
  7. 7.
    Szabados E, Fischer GM, Toth K, Csete B, Nemeti B, Trombitas K (1999) Role of reactive oxygen species and poly-ADP-ribose polymerase in the development of AZT-induced cardiomyopathy in rat. Free Rad Biol Med 26: 309–317PubMedCrossRefGoogle Scholar
  8. 8.
    Skuta G, Fischer GM, Janaky T, Kele Z, Szabo P, Tozser J (1999) Molecular mechanism of the short-term cardiotoxicity caused by 2’,3’-dideoxycytidine (ddC): modulation of reactive oxygen species levels and ADP-ribosylation reactions. Biochem Pharmacol 58: 1915–1925PubMedCrossRefGoogle Scholar
  9. 9.
    Pieper AA, Blackshaw S, Clements EE, Brat DJ, Krug DK, White AJ (2000) Poly(ADP-ribosyl)ation basally activated by DNA strand breaks reflects glutamate-nitric oxide neurotransmission. Proc Natl Acad Sci USA 97: 1845–1850PubMedCrossRefGoogle Scholar
  10. 10.
    Gilad E, Zingarelli B, Salzman AL, Szabo C (1997) Protection by inhibition of poly ( ADP-ribose) synthetase against oxidant injury in cardiac myoblasts in vitro. J Mol Cell Cardiol 29: 2585–2597Google Scholar
  11. 11.
    Szabó C, Zingarelli B, Salzman AL (1996) Peroxynitrite-mediated activation of poly-ADP ribosyl synthetase contributes to the vascular failure in shock. In: Okada K, Ogata H (ed) Shock: From Molecular and Cellular Level to Whole Body. Excerpta Medica International Congress Series 1102. Elsevier, Ansterdam, pp 3–14Google Scholar
  12. 12.
    Zingarelli B, Cuzzocrea S, Zsengeller Z, Salzman AL, Szabó C (1997) Inhibition of poly ( ADP ribose) synthetase protects against myocardial ischemia and reperfusion injury. Cardiovasc Res 36: 205–215Google Scholar
  13. 13.
    Thiemermann C, Bowes J, Myint FP, Vane JR (1997) Inhibition of the activity of poly ( ADP ribose) synthetase reduces ischemia-reperfusion injury in the heart and skeletal muscle. Proc Natl Acad Sci USA 94: 679–683Google Scholar
  14. 14.
    Bowes J, Ruetten H, Martorana PA, Stockhausen H, Thiemermann C (1998) Reduction of myocardial reperfusion injury by an inhibitor of poly ( ADP-ribose) synthetase in the pig. Eur J Pharmacol 359: 143–150Google Scholar
  15. 15.
    Bowes J, Piper J, Thiemermann C (1998) Inhibitors of the activity of poly ( ADP-ribose) synthetase reduce the cell death caused by hydrogen peroxide in human cardiac myoblasts. Br J Pharmacol 124: 1760–1766Google Scholar
  16. 16.
    Bowes J, McDonald MC, Piper J, Thiemermann C (1999) Inhibitors of poly ( ADP-ribose) synthetase protect rat cardiomyocytes against oxidant stress. Cardiovasc Res 41: 126–134Google Scholar
  17. 17.
    Docherty JC, Kuzio B, Silvester JA, Bowes J, Thiemermann C (1999) An inhibitor of poly ( ADP-ribose) synthetase activity reduces contractile dysfunction and preserves high energy phosphate levels during reperfusion of the ischaemic rat heart. Br J Pharmacol 127: 15181524Google Scholar
  18. 18.
    Janero DR, Hreniuk D, Sharif HM, Prout KC (1993) Hydroperoxide-induced oxidative stress alters pyridine nucleotide metabolism in neonatal heart muscle cells. Am J Physiol 264: C1401 - C1410PubMedGoogle Scholar
  19. 19.
    Szabados E, Fischer GM, Gallyas F Jr, Kispal G, Sumegi B (1999) Enhanced ADP-ribosylation and its diminution by lipoamide after ischemia-reperfusion in perfused rat heart. Free Rad Biol Med 27: 1103–1113PubMedCrossRefGoogle Scholar
  20. 20.
    Faro R, Toyoda Y, McCully J, et al (2002) Protective effect on regional myocardial function and infarct size induced by PJ34: a novel poly (ADP-ribose) synthetase inhibitor. Ann Thorac Surg (in press)Google Scholar
  21. 21.
    Zingarelli B, Salzman AL, Szabó C (1998) Genetic disruption of poly (ADP-ribose) synthetase inhibits the expression of P-selectin and intercellular adhesion molecule-1 in myocardial ischemia-reperfusion injury. Circ Res 83: 85–94PubMedCrossRefGoogle Scholar
  22. 22.
    Yang Z, Zingarelli B, Szabo C (2000) Effect of genetic disruption of poly ( ADP-ribose) synthetase on delayed production of inflammatory mediators and delayed necrosis during myocardial ischemia-reperfusion injury. Shock 13: 60–66Google Scholar
  23. 23.
    Grupp IL, Jackson TM, Hake P, Grupp G, Szabó C (1999) Protection against hypoxia-reoxygenation in the absence of poly ( ADP-ribose) synthetase in isolated working hearts. J Mol Cell Cardiol 31: 297–303Google Scholar
  24. 24.
    Liaudet L, Yang Z, Affar B, Szabó C (2001) Myocardial ischemic preconditioning in rodents is dependent on poly ( ADP-ribose) synthetase. Mol Med 7: 406–417Google Scholar
  25. 25.
    Garcia Soriano F, Virag L, Jagtap P, et al (2001) Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation. Nat Med 7: 108–113CrossRefGoogle Scholar
  26. 26.
    Jagtap P, Soriano FG, Virag L, Liaudet L, Mabley J, Szabó C (2002) Novel phenanthridinone inhibitors of poly(ADP-ribose) synthetase: potent cytoprotective and anti-shock agents. Crit Care Med (in press)Google Scholar
  27. 27.
    Virag L, Salzman AL, Szabo C (1998) Poly(ADP-ribose) synthetase activation mediates mitochondrial injury during oxidant-induced cell death. J Immunol 161: 3753–3759PubMedGoogle Scholar
  28. 28.
    H Halmosi R, Berente Z, Osz E, Toth K, Literati-Nagy P, Sumegi B (2001) Effect of poly(ADP-ribose) polymerase inhibitors on the ischemia-reperfusion-induced oxidative cell damage and mitochondrial metabolism in Langendorff heart perfusion system. Mol Pharmacol 59: 1497–505PubMedGoogle Scholar
  29. 29.
    Szabó C, Wong HR, Bauer PI, Kirsten E, O’Connor M, Zingarelli B (1997) Regulation of components of the inflammatory response by 5-iodo-6-amino-1,2-benzopyrone, and inhibitor of poly ( ADP-ribose) synthetase and pleiotropic modifier of cellular signal pathways. Int J Oncol 10: 1093–1101Google Scholar
  30. 30.
    Roebuck KA, Rahman A, Lakshminarayanan V, Janakidevi K, Malik AB (1995) H202 and tumor necrosis factor-activate intercellular adhesion molecule 1 (ICAM-1) gene transcription through distinct cis-regulatory elements within the ICAM-1 promoter. J Biol Chem 270: 18966–18974PubMedCrossRefGoogle Scholar
  31. 31.
    Oliver FJ, Menissier-de Murcia J, Nacci C, Decker P, Andriantsitohaina R, Muller S (1999) Resistance to endotoxic shock as a consequence of defective NF-kappaB activation in poly (ADP-ribose) polymerase-1 deficient mice. EMBO J 18: 4446–4454PubMedCrossRefGoogle Scholar
  32. 32.
    Simbulan-Rosenthal CM, Ly DH, Rosenthal DS, Konopka G, Luo R, Wang ZQ (2000) Mis-regulation of gene expression in primary fibroblasts lacking poly(ADP-ribose) polymerase. Proc Natl Acad Sci USA 97: 11274–11279PubMedCrossRefGoogle Scholar
  33. 33.
    Szabó C, Lim LHK, Cuzzocrea S, Getting SJ, Zingarelli B, Flower RJ (1997) Inhibition of poly ( ADP-ribose) synthetase attenuates neutrophil recruitment and exerts antiinflammatory effects. J Exp Med 186: 1041–1049Google Scholar
  34. 34.
    Szabo C, Virag L, Cuzzocrea S, Scott GS, Hake P, O’Connor MP (1998) Protection against peroxynitrite-induced fibroblast injury and arthritis development by inhibition of poly(ADP-ribose) synthase. Proc Natl Acad Sci USA 95: 3867–3872PubMedCrossRefGoogle Scholar
  35. 35.
    Zingarelli B, Szabó C, Salzman AL (1999) Blockade of poly ( ADP-ribose) synthetase inhibits neutrophil recruitment, oxidant generation, and mucosal injury in murine colitis, Gastroenterology 116: 335–345Google Scholar
  36. 36.
    Szabo C, Cuzzocrea S, Zingarelli B, O’Connor M, Salzman AL (1997) Endothelial dysfunction in a rat model of endotoxic shock. Importance of the activation of poly ( ADP-ribose) synthetase by peroxynitrite. J Clin Invest 100: 723–735Google Scholar
  37. 37.
    Sosulina LI, Sukhova GS, Chudnyi MN, Ashmarin IP (1999) The action of ADP ribose on the mechanical and bioelectrical activity of the frog. Ross Fiziol Zh Im I M Sechenova 85: 508–514PubMedGoogle Scholar
  38. 38.
    Freude B, Masters TN, Robicsek F, Fokin A, Kostin S, Zimmermann R (2000) Apoptosis is initiated by myocardial ischemia and executed during reperfusion. J Mol Cell Cardiol 32: 197–208PubMedCrossRefGoogle Scholar
  39. 39.
    De Boer RA, van Veldhuisen DJ, van Der Wijk J, Brouwer RM, de Jonge N, Cole GM (2000) Additional use of immunostaining for active caspase 3 and cleaved actin and PARP fragments to detect apoptosis in patients with chronic heart failure. J Cardiac Failure 6: 330–337CrossRefGoogle Scholar
  40. 40.
    Virag L, Scott GS, Cuzzocrea S, Marmer D, Salzman AL, Szabo C (1998) Peroxynitrite-induced thymocyte apoptosis: the role of caspases and poly (ADP-ribose) synthetase ( PARS) activation. Immunology 94: 345–355Google Scholar
  41. 41.
    Herceg Z, Wang ZQ (1999) Failure of poly(ADP-ribose) polymerase cleavage by caspases leads to induction of necrosis and enhanced apoptosis. Mol Cell Biol 19: 5124–5133PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • C. Szabó
  • L. Liaudet

There are no affiliations available

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