Activation of poly(ADP-ribose) polymerase by myocardial ischemia and coronary reperfusion in human circulating leukocytes

Emese Tóth-Zsámboki, Eszter Horváth, Katarina Vargova, Eszter Pankotai, Kanneganti Murthy, Zsuzsanna Zsengellér, Tamás Bárány, Tamás Pék, Katalin Fekete, Róbert Gábor Kiss, István Préda, Zsombor Lacza, Domokos Gerö, Csaba Szabo

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Reactive free radical and oxidant production leads to DNA damage during myocardial ischemia/reperfusion. Consequent overactivation of poly(ADP-ribose) polymerase (PARP) promotes cellular energy deficit and necrosis. We hypothesized that PARP is activated in circulating leukocytes in patients with myocardial infarction and reperfusion during primary percutaneous coronary intervention (PCI). In 15 patients with ST segment elevation acute myocardial infarction, before and after primary PCI and 24 and 96 h later, we determined serum hydrogen peroxide concentrations, plasma levels of the oxidative DNA adduct 8-hydroxy-2′-deoxyguanosine (8OHdG), tyrosine nitration, PARP activation, and translocation of apoptosis-inducing factor (AIF) in circulating leukocytes, Plasma 8OHdG levels and leukocyte tyrosine nitration were rapidly increased by PCI. Similarly, poly(ADP-ribose) content of the leukocytes increased in cells isolated just after PCI, indicating immediate PARP activation triggered by reperfusion of the myocardium. In contrast, serum hydrogen peroxide concentrations and the translocation of AIF gradually increased over time and were most pronounced at 96 h. Reperfusion-related oxidative/nitrosative stress triggers DNA damage, which leads to PARP activation in circulating leukocytes. Translocation of AIF and lipid peroxidation occurs at a later stage. These results represent the first direct demonstration of PARP activation in human myocardial infarction. Future work is required to test whether pharmacological inhibition of PARP may offer myocardial protection during primary PCI.

Original languageEnglish (US)
Pages (from-to)221-228
Number of pages8
JournalMolecular Medicine
Volume12
Issue number9-10
DOIs
StatePublished - Sep 2006
Externally publishedYes

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Myocardial Reperfusion
Poly(ADP-ribose) Polymerases
Myocardial Ischemia
Leukocytes
Percutaneous Coronary Intervention
Apoptosis Inducing Factor
Hydrogen Peroxide
DNA Damage
Reperfusion
Tyrosine
Myocardial Infarction
Poly Adenosine Diphosphate Ribose
DNA Adducts
Serum
Oxidants
Lipid Peroxidation
Free Radicals
Myocardium
Oxidative Stress
Necrosis

ASJC Scopus subject areas

  • Genetics

Cite this

Activation of poly(ADP-ribose) polymerase by myocardial ischemia and coronary reperfusion in human circulating leukocytes. / Tóth-Zsámboki, Emese; Horváth, Eszter; Vargova, Katarina; Pankotai, Eszter; Murthy, Kanneganti; Zsengellér, Zsuzsanna; Bárány, Tamás; Pék, Tamás; Fekete, Katalin; Kiss, Róbert Gábor; Préda, István; Lacza, Zsombor; Gerö, Domokos; Szabo, Csaba.

In: Molecular Medicine, Vol. 12, No. 9-10, 09.2006, p. 221-228.

Research output: Contribution to journalArticle

Tóth-Zsámboki, E, Horváth, E, Vargova, K, Pankotai, E, Murthy, K, Zsengellér, Z, Bárány, T, Pék, T, Fekete, K, Kiss, RG, Préda, I, Lacza, Z, Gerö, D & Szabo, C 2006, 'Activation of poly(ADP-ribose) polymerase by myocardial ischemia and coronary reperfusion in human circulating leukocytes', Molecular Medicine, vol. 12, no. 9-10, pp. 221-228. https://doi.org/10.2119/2006-00055.Toth-Zsamboki
Tóth-Zsámboki, Emese ; Horváth, Eszter ; Vargova, Katarina ; Pankotai, Eszter ; Murthy, Kanneganti ; Zsengellér, Zsuzsanna ; Bárány, Tamás ; Pék, Tamás ; Fekete, Katalin ; Kiss, Róbert Gábor ; Préda, István ; Lacza, Zsombor ; Gerö, Domokos ; Szabo, Csaba. / Activation of poly(ADP-ribose) polymerase by myocardial ischemia and coronary reperfusion in human circulating leukocytes. In: Molecular Medicine. 2006 ; Vol. 12, No. 9-10. pp. 221-228.
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AU - Pankotai, Eszter

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AU - Zsengellér, Zsuzsanna

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