Laura Dugo

University of Messina

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Salvatore Cuzzocrea

Saint Louis University

Achille P. Caputi

University of Messina

Emanuela Mazzon

University of Messina

Christoph Thiemermann

William Harvey Research Institute

Ivana Serraino

University of Messina

Rosanna Di Paola

University of Messina

Chiara Fanali

Università Campus Bio-Medico

Luigi Mondello

Università Campus Bio-Medico

Tiziana Genovese

University of Messina

Laura De Gara

Università Campus Bio-Medico

Cooperative Institutions

University of Messina

Università Campus Bio-Medico

William Harvey Research Institute

Sapienza University of Rome

University of Naples Federico II

Queen Mary University of London

Istituti di Ricovero e Cura a Carattere Scientifico

Campus Bio Medico University Hospital

Federico II University Hospital

University of Palermo

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Celecoxib, a selective cyclo-oxygenase-2 inhibitor reduces the severity of experimental colitis induced by dinitrobenzene sulfonic acid in rats

European Journal of Pharmacology (2001)

Salvatore Cuzzocrea Emanuela Mazzon Ivana Serraino Laura Dugo Tommaso Centorrino

Celecoxib

Malondialdehyde

Nitrotyrosine

Intestinal mucosa

10.1016/s0014-2999(01)01403-0

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Citations (56)

INDUCIBLE NITRIC OXIDE SYNTHASE KNOCK OUT MICE EXHIBIT RESISTANCE TO THE ACUTE PANCREATITIS INDUCED BY CERULEIN.

Shock (2001)

T. Centorrino E. Mazzon Laura Dugo A. Ciccolo Fons A. J. van de Loo

Centorrino, T.1; Mazzon, E.2; Dugo, L.3; Ciccolo, A.1; Van de Loo, F. A.J.4; Caputi, A. P.3; Thiemermann, C.5; Cuzzocrea, S.3 Author Information

10.1097/00024382-200106001-00224

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Noncleavable poly(ADP-ribose) polymerase-1 regulates the inflammation response in mice

Journal of Clinical Investigation (2004)

Virginie Pétrilli Zdenko Herceg Paul O. Hassa Nimesh S. A. Patel Rosanna Di Paola

Poly(ADP-ribosyl)ation is rapidly formed in cells following DNA damage and is regulated by poly(ADP-ribose) polymerase-1 (PARP-1). PARP-1 is known to be involved in various cellular processes, such as DNA repair, genomic stability, transcription, and cell death. During apoptosis, PARP-1 is cleaved by caspases to generate 89-kDa and 24-kDa fragments, a hallmark of apoptosis. This cleavage is thought to be a regulatory event for cellular death. In order to understand the biological significance of PARP-1 cleavage, we generated a PARP-1 knockin (PARP-1KI/KI) mouse model, in which the caspase cleavage site of PARP-1, DEVD214, was mutated to render the protein resistant to caspases during apoptosis. While PARP-1KI/KI mice developed normally, they were highly resistant to endotoxic shock and to intestinal and renal ischemia-reperfusions, which were associated with reduced inflammatory responses in the target tissues and cells due to the compromised production of specific inflammatory mediators. Despite normal binding of NF-κB to DNA, NF-κB–mediated transcription activity was impaired in the presence of caspase-resistant PARP-1. This study provides a novel insight into the function of PARP-1 in inflammation and ischemia-related pathophysiologies.

10.1172/jci200421854

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Citations (96)

Online Comprehensive RPLC × RPLC with Mass Spectrometry Detection for the Analysis of Proteome Samples

Analytical Chemistry (2011)

Paola Donato Francesco Cacciola Eduardo Sommella Chiara Fanali Laura Dugo

LC-MS-based shotgun proteomics relies both on the power of the separation techniques and the sensitivity of detection methods. As a viable alternative to classical approaches in this field, we developed a fully automated, comprehensive 2D LC system, in which RPLC × RPLC was coupled to MS detection, for the first time, and applied for the analysis of tryptic digests obtained from α-casein and dephosphorylated α-casein. The use of a significantly different pH in the two dimensions allowed us to attain high peak capacity, despite the employment of novel identical stationary phases. Furthermore, such a combination addresses compatibility issues, thus allowing straightforward interfacing in online 2D LC configuration, as well as direct linkage to a mass spectrometer. A theoretical peak capacity of ca. 8500 was calculated for the setup, employing four serially coupled C18 columns in the first dimension (600 × 2.1 mm, 2.7 μm d.p.), operated under basic conditions, and 3 cm length of the same stationary phase (30 × 4.6 mm, 2.7 μm d.p. column), under acidic conditions, for fast second dimension analysis.

Shotgun proteomics

10.1021/ac102656b

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Citations (61)

Beneficial Effects Of GPI 6150, an Inhibitor of Poly(ADP-Ribose) Polymerase in a Rat Model of Splanchnic Artery Occlusion and Reperfusion

Shock (2002)

Emanuela Mazzon Laura Dugo Angelina De Sarro Jia-He Li Achille P. Caputi

The aim of the present study was to investigate the effects of GPI 6150, a new poly(ADP-ribose) polymerase (PARP) inhibitor, in the pathogenesis of splanchnic artery occlusion (SAO) shock. SAO shock was induced in rats by clamping both the superior mesenteric artery and the celiac trunk for 45 min, followed by reperfusion. At 60 min after reperfusion, SAO-shocked rats developed a significant fall in mean arterial blood pressure, significant increase of tissue myeloperoxidase activity (111 +/- 4.3 U/100 mg wet tissue vs. 28 +/- 3.2 U/100 mg wet tissue of sham-operated rats), and marked histological injury to the distal ileum and a significant mortality (0% survival at 2 h after reperfusion). Immuno-histochemical examination demonstrated a marked increase in the immunoreactivity to PARP, P-selectin, and intercellular adhesion molecule (ICAM-1) in the necrotic ileum. GPI 6150 treatment significantly improved mean arterial blood pressure, prevented the infiltration of neutrophils (72 +/- 3.6 U/100 mg wet tissue) into the reperfused intestine, improved the histological status of the reperfused tissues, markedly reduced the intensity of P-selectin and ICAM-1 in tissue section from SAO-shocked rats, and improved survival. In conclusion, our study demonstrates that GPI 6150 exerts multiple protective effects in splanchnic artery occlusion/reperfusion shock.

10.1097/00024382-200203000-00011

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Citations (39)

Role of 5-lipoxygenase in the multiple organ failure induced by zymosan

Intensive Care Medicine (2004)

Salvatore Cuzzocrea Antonietta Rossi Ivana Serraino Rosanna Di Paola Laura Dugo

Zymosan

Pain medicine

10.1007/s00134-004-2353-y

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Citations (21)

Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-γ, reduces the development of nonseptic shock induced by zymosan in mice*

Critical Care Medicine (2004)

Salvatore Cuzzocrea Maria Barbara Pisano Laura Dugo Angela Ianaro Nimesh S. A. Patel

Objective Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid, and thyroid hormone receptors. The PPAR-γ receptor subtype appears to play a pivotal role in the regulation of cellular proliferation and inflammation. Rosiglitazone (Avandia) is a PPAR-γ agonist (the most potent PPAR-γ agonist of the thiazolidinedione antidiabetics). In the present study, we investigated the effects of rosiglitazone on the development of nonseptic shock caused by zymosan in mice. Design Experimental study. Setting University laboratory. Subjects Male CD mice. Interventions We investigated the effects of rosiglitazone (3 mg/kg) on the development of nonseptic shock caused by zymosan (500 mg/kg, administered intraperitoneally as a suspension in saline) in mice. Measurements and Main Results Organ failure and systemic inflammation in rats were assessed 18 hrs after administration of zymosan and/or rosiglitazone and monitored for 12 days (for loss of body weight and mortality rate). Treatment of mice with rosiglitazone (3 mg/kg intraperitoneally, 1 and 6 hrs after zymosan) attenuated the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan. Rosiglitazone also attenuated the lung, liver, and pancreatic injury and renal dysfunction caused by zymosan as well as the increase in myeloperoxidase activity and malondialdehyde concentrations caused by zymosan in the lung and intestine. Immunohistochemical analysis for inducible nitric oxide synthase, nitrotyrosine, and poly(adenosine diphosphate-ribose) revealed positive staining in lung and intestine tissues obtained from zymosan-treated mice. The degree of staining for nitrotyrosine, inducible nitric oxide synthase, and poly(adenosine diphosphate-ribose) was markedly reduced in tissue sections obtained from zymosan-treated mice that received rosiglitazone. To elucidate whether the protective effects of rosiglitazone are related to activation of the PPAR-γ receptor, we also investigated the effect of a PPAR-γ antagonist, GW 9662, on the protective effects of rosiglitazone. GW 9662 (1 mg/kg administered intraperitoneally 30 mins before treatment with rosiglitazone) significantly antagonized the effect of the PPAR-γ agonist and thus abolished the protective effect. Conclusions This study provides evidence, for the first time, that rosiglitazone attenuates the degree of zymosan-induced nonseptic shock in mice.

Rosiglitazone

Zymosan

Peroxisome proliferator

10.1097/01.ccm.0000109446.38675.61

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Citations (52)

Protective effects ofn‐acetylcysteine on lung injury and red blood cell modification induced by carrageenan in the rat

The FASEB Journal (2001)

Salvatore Cuzzocrea Emanuela Mazzon Laura Dugo Ivana Serraino A Ciccolo

Oxidative stress has been suggested as a potential mechanism in the pathogenesis of lung inflammation. The pharmacological profile of n-acetylcysteine (NAC), a free radical scavenger, was evaluated in an experimental model of lung injury (carrageenan-induced pleurisy). Injection of carrageenan into the pleural cavity of rats elicited an acute inflammatory response characterized by fluid accumulation in the pleural cavity that contained many neutrophils (PMNs), an infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate, tumor necrosis factor alpha, and interleukin 1beta. All parameters of inflammation were attenuated by NAC treatment. Furthermore, carrageenan induced an up-regulation of the adhesion molecules ICAM-1 and P-selectin, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS), as determined by immunohistochemical analysis of lung tissues. The degree of staining for the ICAM-1, P-selectin, nitrotyrosine, and PARS was reduced by NAC. In vivo NAC treatment significantly reduced peroxynitrite formation as measured by the oxidation of the fluorescent dihydrorhodamine-123, prevented the appearance of DNA damage, an decrease in mitochondrial respiration, and partially restored the cellular level of NAD+ in ex vivo macrophages harvested from the pleural cavity of rats subjected to carrageenan-induced pleurisy. A significant alteration in the morphology of red blood cells was observed 24 h after carrageenan administration. NAC treatment has the ability to significantly diminish the red blood cell alteration. Our results clearly demonstrate that NAC treatment exerts a protective effect and clearly indicate that NAC offers a novel therapeutic approach for the management of lung injury where radicals have been postulated to play a role.

Nitrotyrosine

Carrageenan

Pleurisy

10.1096/fj.00-0526hyp

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Citations (103)

Calpain Inhibitor I Reduces the Development of Acute and Chronic Inflammation

American Journal Of Pathology (2000)

Salvatore Cuzzocrea Michelle C. McDonald Emanuela Mazzon Dilani Siriwardena Ivana Serraino

Calpastatin

Pleurisy

Nitrotyrosine