Peroxynitrite-mediated DNA strand breakage activates poly (ADP-ribose) synthetase and causes cellular energy depletion in carrageenan-induced pleurisy

Immunology
S CuzzocreaB Zingarelli

Abstract

The aim of the present study was to investigate the role of poly (ADP-ribose) synthetase in acute local inflammation (carrageenan-induced pleurisy), where oxyradicals, nitric oxide and peroxynitrite are known to play a crucial role in the inflammatory process. DNA single-strand breakage and activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS) triggers an energy-consuming, inefficient repair cycle, which contributes to peroxynitrite-induced cellular injury. Here we investigated whether peroxynitrite production and PARS activation are involved in cytotoxicity in macrophages collected from rats subjected to carrageenan-induced pleurisy. Macrophages harvested from the pleural cavity exhibited a significant production of peroxynitrite, as measured by the oxidation of the fluorescent dye dihydrorhodamine 123, and by nitrotyrosine Western blotting at 4 hr after carrageenan injection. Furthermore, carrageenan-induced pleurisy caused a suppression of macrophage mitochondrial respiration, DNA strand breakage, activation of PARS and reduction of NAD+ cellular levels. In vivo treatment with 3-aminobenzamide (10 mg/kg intraperitoneally, 1 hr after carrageenin injection) significantly inhibited the decrease in mitochondrial r...Continue Reading

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Citations

Oct 23, 2008·Inflammation·Rajendran MythilypriyaPanchanadam Sachdanandam
Jan 28, 2004·European Journal of Pharmacology·Stefania MarzoccoGiuseppina Autore
Sep 30, 2000·European Journal of Pharmacology·S CuzzocreaC Thiemermann
Aug 30, 2001·European Journal of Pharmacology·S Cuzzocrea, R J Reiter
Jul 31, 1998·European Journal of Pharmacology·C Szabó
Jul 8, 1999·European Journal of Pharmacology·S CuzzocreaA P Caputi
Mar 10, 2000·European Journal of Pharmacology·S CuzzocreaC Thiemermann
Nov 23, 2000·British Journal of Pharmacology·S CuzzocreaA P Caputi
Feb 22, 2001·British Journal of Pharmacology·D SalveminiS Cuzzocrea
Jan 30, 2002·British Journal of Pharmacology·Salvatore CuzzocreaChristoph Thiemermann
Nov 28, 2002·Alimentary Pharmacology & Therapeutics·L Kruidenier, H W Verspaget
Nov 9, 2000·American Journal of Respiratory and Critical Care Medicine·S CuzzocreaA P Caputi
Nov 1, 2007·Respiratory Research·Emanuela Mazzon, Salvatore Cuzzocrea
May 15, 2007·Brain Research Reviews·Alfredo ContiFrancesco Tomasello
Aug 16, 2005·Journal of Pineal Research·Tiziana GenoveseSalvatore Cuzzocrea
Feb 24, 2005·Journal of Pineal Research·Tiziana GenoveseSalvatore Cuzzocrea
Feb 3, 2005·Journal of Pineal Research·Antonio J Jiménez-CalianiCarmen Osuna
Feb 11, 2004·British Journal of Pharmacology·Laura DugoSalvatore Cuzzocrea
Aug 24, 2004·European Journal of Pharmacology·Clara Di FilippoMichele D'Amico
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Jan 27, 2017·International Journal of Molecular Sciences·Dominic M MaggioDamien D Pearse
Jul 11, 2006·The Journal of Pharmacology and Experimental Therapeutics·Salvatore CuzzocreaZhao-Qi Wang

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