TY - JOUR AU - Regdon, Zsolt AU - Robaszkiewicz, Agnieszka AU - Kovács, Katalin AU - Rygielska, Żaneta AU - Hegedűs, Csaba AU - Bodoor, Khaldon AU - Szabó, Éva AU - Virág, László TI - LPS protects macrophages from AIF-independent parthanatos by downregulation of PARP1 expression, induction of SOD2 expression, and a metabolic shift to aerobic glycolysis JF - FREE RADICAL BIOLOGY AND MEDICINE J2 - FREE RADICAL BIO MED VL - 131 PY - 2019 SP - 184 EP - 196 PG - 13 SN - 0891-5849 DO - 10.1016/j.freeradbiomed.2018.11.034 UR - https://m2.mtmt.hu/api/publication/30347746 ID - 30347746 LA - English DB - MTMT ER - TY - JOUR AU - Abu-El-Haija, Maisam AU - Gukovskaya, Anna S. AU - Andersen, Dana K. AU - Gardner, Timothy B. AU - Hegyi, Péter AU - Pandol, Stephen J. AU - Papachristou, Georgios I. AU - Saluja, Ashok K. AU - Singh, Vikesh K. AU - Uc, Aliye AU - Wu, Bechien U. TI - Accelerating the Drug Delivery Pipeline for Acute and Chronic Pancreatitis. Summary of the Working Group on Drug Development and Trials in Acute Pancreatitis at the National Institute of Diabetes and Digestive and Kidney Diseases Workshop TS - Summary of the Working Group on Drug Development and Trials in Acute Pancreatitis at the National Institute of Diabetes and Digestive and Kidney Diseases Workshop JF - PANCREAS J2 - PANCREAS VL - 47 ET - 0 PY - 2018 IS - 10 SP - 1185 EP - 1192 PG - 8 SN - 0885-3177 DO - 10.1097/MPA.0000000000001175 UR - https://m2.mtmt.hu/api/publication/30311195 ID - 30311195 N1 - Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Pancreas Care Center, 3333 Burnet Ave MLC 2010, Cincinnati, OH 45229, United States Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH, United States Department of Medicine, University of California, Los Angeles, United States Pancreatic Research Group, UCLA, VA Greater Los Angeles Healthcare System, Los Angeles, CA, United States Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States Department of Medicine, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine, Darmouth University, Hanover, NH, United States MTA-SZTE Translational Gastroenterology Research Group, University of Szeged, Szeged, Hungary Institute for Translational Medicine, First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, United States Division of Gastroenterology and Hepatology, Veterans Affairs Pittsburgh Health System, Pittsburgh, PA, United States Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, United States Division of Gastroenterology, Department of Medicine, University of John's Hopkins, Baltimore, MD, United States Stead Family Department of Pediatrics, University of Iowa, Stead Family Children's Hospital, Iowa City, IA, United States Center for Pancreatic Care, Department of Gastroenterology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, United States Cited By :18 Export Date: 26 January 2024 CODEN: PANCE Correspondence Address: Abu-El-Haija, M.; Division of Gastroenterology, 3333 Burnet Ave MLC 2010, United States; email: Maisam.Haija@cchmc.org AB - A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to focus on research gaps and opportunities on drug development for pancreatitis. This conference was held on July 25, 2018, and structured into 3 working groups (WG): acute pancreatitis (AP) WG, recurrent AP WG, and chronic pancreatitis WG. This article reports the outcome of the work accomplished by the AP WG to provide the natural history, epidemiology, and current management of AP; inform about the role of preclinical models in therapy selection; and discuss clinical trial designs with clinical and patient-reported outcomes to test new therapies. LA - English DB - MTMT ER - TY - JOUR AU - Bodnár, Edina AU - Bakondi, Edina AU - Kovács, Katalin AU - Hegedűs, Csaba AU - Lakatos, Petra AU - Robaszkiewicz, Agnieszka AU - Regdon, Zsolt AU - Virág, László AU - Szabó, Éva TI - Redox Profiling Reveals Clear Differences between Molecular Patterns of Wound Fluids from Acute and Chronic Wounds JF - OXIDATIVE MEDICINE AND CELLULAR LONGEVITY J2 - OXID MED CELL LONGEV VL - 2018 PY - 2018 PG - 12 SN - 1942-0900 DO - 10.1155/2018/5286785 UR - https://m2.mtmt.hu/api/publication/30321123 ID - 30321123 AB - Wound healing is a complex multiphase process which can be hampered by many factors including impaired local circulation, hypoxia, infection, malnutrition, immunosuppression, and metabolic dysregulation in diabetes. Redox dysregulation is a common feature of many skin diseases demonstrated by virtually all cell types in the skin with overproduction of reactive oxygen and nitrogen species. The objective of this study was to characterize the redox environment in wound fluids and sera from patients suffering from chronic leg ulcers (n = 19) and acute wounds (bulla fluids from second degree burns; n = 11) with serum data also compared to those from healthy volunteers (n = 7). Significantly higher concentrations of TNF-alpha, interleukine-8, vascular endothelial growth factor, and lactate dehydrogenase (measure of cell damage) were found in fluids from chronic wounds compared to acute ones. The extent of protein carbonylation (measure of protein oxidation), lipid peroxidation, and tyrosine nitration (indicator of peroxynitrite production) was similar in acute and chronic wound fluids, while radical scavenging activity and glutathione (GSH) levels were elevated in chronic wound fluids compared to acute wounds. Sera were also assessed for the same set of parameters with no significant differences detected. Nitrotyrosine (the footprint of the potent oxidant peroxynitrite) and poly(ADP-ribose) (the product of the DNA damage sensor enzyme PARP-1) could be detected in wound biopsies. Our data identify multiple signs of redox stress in chronic wounds with notable differences. In chronic wounds, elevations in antioxidant levels/activities may indicate compensatory mechanisms against inflammation. The presence of nitrotyrosine and poly(ADP-ribose) in tissues from venous leg ulcers indicate peroxynitrite production and PARP activation in chronic wounds. LA - English DB - MTMT ER - TY - JOUR AU - Venglovecz, Viktória AU - Pallagi, Petra AU - Kemény, Lajos Vince AU - Balázs, Anita AU - Balla, Zsolt AU - Becskeházi, Eszter AU - Gál, Eleonóra AU - Tóth, Emese AU - Zvara, Ágnes AU - Puskás, László AU - Borka, Katalin AU - Sendler, M AU - Lerch, MM AU - Mayerle, J AU - Kuhn, JP AU - Rakonczay, Zoltán AU - Hegyi, Péter TI - The Importance of Aquaporin 1 in Pancreatitis and Its Relation to the CFTR Cl- Channel JF - FRONTIERS IN PHYSIOLOGY J2 - FRONT PHYSIOL VL - 9 PY - 2018 PG - 15 SN - 1664-042X DO - 10.3389/fphys.2018.00854 UR - https://m2.mtmt.hu/api/publication/3399461 ID - 3399461 N1 - Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary First Department of Medicine, University of Szeged, Szeged, Hungary Department of Pathophysiology, University of Szeged, Szeged, Hungary Laboratory of Functional Genomics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary Second Department of Pathology, Semmelweis University, Budapest, Hungary Department of Medicine A, University Medicine Greifswald, University of Greifswald, Greifswald, Germany Department of Medicine II, Klinikum Grosshadern, Universitätsklinikum der Ludwig-Maximilians-Universität München, Munich, Germany Institute of Radiology, University Medicine Greifswald, University of Greifswald, Greifswald, Germany Institute and Policlinic of Radiology, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany MTA-SZTE Translational Gastroenterology Research Group, University of Szeged, Szeged, Hungary Institute for Translational Medicine and First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary Cited By :27 Export Date: 26 January 2024 Correspondence Address: Hegyi, P.; First Department of Medicine, Hungary; email: hegyi.peter@pte.hu AB - Aquaporins (AQPs) facilitate the transepithelial water flow involved in epithelial fluid secretion in numerous tissues; however, their function in the pancreas is less characterized. Acute pancreatitis (AP) is a serious disorder in which specific treatment is still not possible. Accumulating evidence indicate that decreased pancreatic ductal fluid secretion plays an essential role in AP; therefore, the aim of this study was to investigate the physiological and pathophysiological role of AQPs in the pancreas. Expression and localization of AQPs were investigated by real-time PCR and immunocytochemistry, whereas osmotic transmembrane water permeability was estimated by the dye dilution technique, in Capan-1 cells. The presence of AQP1 and CFTR in the mice and human pancreas were investigated by immunohistochemistry. Pancreatic ductal HCO3- and fluid secretion were studied on pancreatic ducts isolated from wild-type (WT) and AQP1 knock out (KO) mice using microfluorometry and videomicroscopy, respectively. In vivo pancreatic fluid secretion was estimated by magnetic resonance imaging. AP was induced by intraperitoneal injection of cerulein and disease severity was assessed by measuring biochemical and histological parameters. In the mice, the presence of AQP1 was detected throughout the whole plasma membrane of the ductal cells and its expression highly depends on the presence of CFTR Cl- channel. In contrast, the expression of AQP1 is mainly localized to the apical membrane of ductal cells in the human pancreas. Bile acid treatment dose- and time-dependently decreased mRNA and protein expression of AQP1 and reduced expression of this channel was also demonstrated in patients suffering from acute and chronic pancreatitis. HCO3- and fluid secretion significantly decreased in AQP1 KO versus WT mice and the absence of AQP1 also worsened the severity of pancreatitis. Our results suggest that AQP1 plays an essential role in pancreatic ductal fluid and HCO3- secretion and decreased expression of the channel alters fluid secretion which probably contribute to increased susceptibility of the pancreas to inflammation. LA - English DB - MTMT ER - TY - JOUR AU - Lakatos, Petra AU - Hegedűs, Csaba AU - Ayestarán, NS AU - Juarranz, Á AU - E Kövér, Katalin AU - Szabó, Éva AU - Virág, László TI - The PARP inhibitor PJ-34 sensitizes cells to UVA-induced phototoxicity by a PARP independent mechanism JF - MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS J2 - MUTAT RES-FUND MOL M VL - 790 PY - 2016 SP - 31 EP - 40 PG - 10 SN - 0027-5107 DO - 10.1016/j.mrfmmm.2016.07.001 UR - https://m2.mtmt.hu/api/publication/3092000 ID - 3092000 LA - English DB - MTMT ER - TY - JOUR AU - Párniczky, Andrea AU - Kui, Balázs AU - Szentesi, Andrea Ildikó AU - Balázs, Anita AU - Szűcs, Ákos AU - Mosztbacher, Dóra AU - Czimmer, József AU - Sarlós, Patrícia AU - Bajor, Judit AU - Gódi, Szilárd AU - Vincze, Áron AU - Illés, Anita AU - Szabó, Imre AU - Pár, Gabriella AU - Takács, Tamás AU - Czakó, László AU - Szepes, Zoltán AU - Rakonczay, Zoltán AU - Izbéki, Ferenc AU - Gervain, Judit AU - Szabó-Halász, Adrienn AU - Novak, J AU - Crai, S AU - Hritz, István AU - Gog, C AU - Sümegi, János AU - Golovics, Petra Anna AU - Varga, M AU - Bod, B AU - Hamvas, József Péter AU - Varga-Muller, M AU - Papp, Z AU - Sahin-Tóth, Miklós AU - Hegyi, Péter TI - Prospective, Multicentre, Nationwide Clinical Data from 600 Cases of Acute Pancreatitis JF - PLOS ONE J2 - PLOS ONE VL - 11 PY - 2016 IS - 10 PG - 19 SN - 1932-6203 DO - 10.1371/journal.pone.0165309 UR - https://m2.mtmt.hu/api/publication/3134541 ID - 3134541 N1 - Funding Agency and Grant Number: Hungarian Scientific Research Fund [K116634]; Hungarian Academy of Sciences [LP2014-10/2014]; [GINOP-2.3.2-15-2016-00015] Funding text: Our research was supported by the Hungarian Scientific Research Fund (K116634) and the Momentum Grant of the Hungarian Academy of Sciences (LP2014-10/2014) and GINOP-2.3.2-15-2016-00015. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Our research was supported by the Hungarian Scientific Research Fund (K116634) and the Momentum Grant of the Hungarian Academy of Sciences (LP2014-10/2014) and GINOP-2.3.2-15-2016-00015. This manuscript was submitted on behalf of the HPSG. We are thankful to the members of the HPSG, who were actively involved in this study: Andrea Parniczky, Balazs Kui, Andrea Szentesi, Anita Balazs, Akos Szucs, Dora Mosztbacher, Jozsef Czimmer, Patricia Sarlos, Judit Bajor, Szilard Godi, Aron Vincze, Anita Illes, Imre Szabo, Gabriella Par, Tamas Takacs, Laszlo Czako Zoltan Szepes, Zoltan Rakonczay, Ferenc Izbeki, Judit Gervain, Adrienn Halasz, Janos Novak, Stefan Crai, Istvan Hritz, Csaba Gog, Janos Sumegi, Petra Golovics, Marta Varga, Barnabas Bod, Jozsef Hamvas, Monika Varga-Muller, Zsuzsanna Papp, Miklos Sahin-Toth and Peter Hegyi. AB - OBJECTIVE: The aim of this study was to analyse the clinical characteristics of acute pancreatitis (AP) in a prospectively collected, large, multicentre cohort and to validate the major recommendations in the IAP/APA evidence-based guidelines for the management of AP. DESIGN: Eighty-six different clinical parameters were collected using an electronic clinical research form designed by the Hungarian Pancreatic Study Group. PATIENTS: 600 adult patients diagnosed with AP were prospectively enrolled from 17 Hungarian centres over a two-year period from 1 January 2013. MAIN RESULTS: With respect to aetiology, biliary and alcoholic pancreatitis represented the two most common forms of AP. The prevalence of biliary AP was higher in women, whereas alcoholic AP was more common in men. Hyperlipidaemia was a risk factor for severity, lack of serum enzyme elevation posed a risk for severe AP, and lack of abdominal pain at admission demonstrated a risk for mortality. Abdominal tenderness developed in all the patients with severe AP, while lack of abdominal tenderness was a favourable sign for mortality. Importantly, lung injury at admission was associated with mortality. With regard to laboratory parameters, white blood cell count and CRP were the two most sensitive indicators for severe AP. The most common local complication was peripancreatic fluid, whereas the most common distant organ failure in severe AP was lung injury. Deviation from the recommendations in the IAP/APA evidence-based guidelines on fluid replacement, enteral nutrition and timing of interventions increased severity and mortality. CONCLUSIONS: Analysis of a large, nationwide, prospective cohort of AP cases allowed for the identification of important determinants of severity and mortality. Evidence-based guidelines should be observed rigorously to improve outcomes in AP. LA - English DB - MTMT ER - TY - JOUR AU - Robaszkiewicz, A AU - Valkó, Zsuzsanna AU - Kovács, Katalin AU - Hegedűs, Csaba AU - Bakondi, Edina AU - Bay, Péter AU - Virág, László TI - The role of p38 signaling and poly(ADP-ribosyl)ation-induced metabolic collapse in the osteogenic differentiation-coupled cell death pathway. JF - FREE RADICAL BIOLOGY AND MEDICINE J2 - FREE RADICAL BIO MED VL - 76 PY - 2014 SP - 69 EP - 79 PG - 11 SN - 0891-5849 DO - 10.1016/j.freeradbiomed.2014.07.027 UR - https://m2.mtmt.hu/api/publication/2719277 ID - 2719277 AB - Osteogenic differentiation is a multistep process regulated by a diverse set of morphogenic and transcription factors. Previously we identified endogenous hydrogen peroxide-induced poly(ADP- ribose) polymerase-1 (PARP1) activation as a mediator of osteodifferentiation and associated cell death. Here we set out to investigate whether or not activation of PARP1 is dependent on DNA breaks and how PARP1 mediates cell death during osteodifferentiation of mesenchymal stem cells and SAOS-2 cells. Here we show that the MAP kinases p38, JNK, and ERK1/2 become activated during the differentiation process. However, only p38 activation depended both on hydrogen peroxide production and on PARP1 activation as the hydrogen peroxide decomposing enzyme catalase, the PARP inhibitor PJ34, and the silencing of PARP1 suppressed p38 activation. Inhibition of p38 suppressed cell death and inhibited osteogenic differentiation (calcium deposition, alkaline phosphatase activity, and marker gene expression) providing further support for the close coupling of osteodifferentiation and cell death. Metabolic collapse appears to be central in the hydrogen peroxide-PARP1-p38 pathway as silencing PARP1 or inhibition of p38 prevented differentiation- associated loss of cellular NAD, inhibition of mitochondrial respiration, and glycolytic activity. We also provide evidence that endogenous hydrogen peroxide produced by the differentiating cells is sufficient to cause detectable DNA breakage. Moreover, p38 translocates from the cytoplasm to the nucleus where it interacts and colocalizes with PARP1 as detected by immunoprecipitation and immunofluorescence, respectively. In summary, hydrogen peroxide-induced PARP1 activation leads to p38 activation and this pathway is required both for the successful completion of the differentiation process and for the associated cell death. LA - English DB - MTMT ER - TY - JOUR AU - Hegedűs, Csaba AU - Lakatos, Petra AU - Kiss, Attila AU - Patonay, Tamás AU - Gergely, Szabolcs Gábor AU - Gregus, Andrea AU - Bay, Péter AU - Haskó, György AU - Szabó, Éva AU - Virág, László TI - Cytoprotective dibenzoylmethane derivatives protect cells from oxidative stress-induced necrotic cell death JF - PHARMACOLOGICAL RESEARCH J2 - PHARMACOL RES VL - 72 PY - 2013 SP - 25 EP - 34 PG - 10 SN - 1043-6618 DO - 10.1016/j.phrs.2013.03.002 UR - https://m2.mtmt.hu/api/publication/2230184 ID - 2230184 N1 - Funding Agency and Grant Number: Bolyai fellowship; Hungarian Science Research Fund [OTKA K73003, K60780, K82009, PD83473]; National Development Agency (Hungary) [TAMOP-4.2.2-08/1-2008-0019, TAMOP 4.2.1./B-09/1/KONV-2010-0007, TAMOP 4.2.2.A-111/1/KONV-2012-0025, TAMOP-4.2.2/B-10/1-2010-0024]; National Innovation Office [TeT_09-2010-0023]; Medical and Health Science Centre of the University of Debrecen [Mec-8/2011] Funding text: This work was supported by Bolyai fellowship to PB, grants from the Hungarian Science Research Fund (OTKA K73003, K60780, K82009, PD83473), from the National Development Agency (Hungary) (TAMOP-4.2.2-08/1-2008-0019, TAMOP 4.2.1./B-09/1/KONV-2010-0007, TAMOP 4.2.2.A-111/1/KONV-2012-0025, TAMOP-4.2.2/B-10/1-2010-0024), from the National Innovation Office (Baross program Seahorse grant; TeT_09-2010-0023) and from the Medical and Health Science Centre of the University of Debrecen (Mec-8/2011). LA - English DB - MTMT ER - TY - JOUR AU - Hegyi, Péter AU - Petersen, OH TI - The Exocrine Pancreas: The Acinar-Ductal Tango in Physiology and Pathophysiology JF - REVIEWS OF PHYSIOLOGY BIOCHEMISTRY AND PHARMACOLOGY J2 - REV PHYSIOL BIOCH P VL - 165 PY - 2013 SP - 1 EP - 30 PG - 30 SN - 9783319009988 SN - 0303-4240 DO - 10.1007/112_2013_14 UR - https://m2.mtmt.hu/api/publication/2363002 ID - 2363002 N1 - Cited By :79 Export Date: 13 July 2023 Correspondence Address: Hegyi, P.; First Department of Medicine, University of Szeged, Koranyi fsr. 8, SZEGED H6720, Hungary; email: hegyi.peter@med.u-szeged.hu Chemicals/CAS: adenosine triphosphate, 15237-44-2, 56-65-5, 987-65-5; alcohol, 64-17-5; angiotensin II, 11128-99-7; bicarbonate, 144-55-8, 71-52-3; calcium, 7440-70-2, 14092-94-5; chloride, 16887-00-6; guanylin, 140653-38-9; hydrogen, 12385-13-6, 1333-74-0; sodium, 7440-23-5; uroguanylin, 154525-25-4; calcium, 14092-94-5, 7440-70-2; Bile Acids and Salts; Calcium, SY7Q814VUP; Ethanol, 3K9958V90M; Bile Acids and Salts; Calcium; Ethanol Funding details: Medical Research Council, MRC, G0700167, G19/22, G19/22/2, MR/J002771/1 Funding details: Hungarian Scientific Research Fund, OTKA, NF100677, NF105758 Funding details: Magyar Tudományos Akadémia, MTA, BO 00174/10/5 Funding details: Nemzeti Fejlesztési Ügynökség, NFÜ, -2012-0035, -2012-0073 Funding text 1: The research on pancreatic ducts was mostly supported by Hungarian National Development Agency grants (TÁMOP-4.2.2.A-11/1/KONV-2012-0035, TÁMOP-4.2.2-A-11/1/KONV-2012-0052 TÁMOP-4.2.2.A-11/1/KONV-2012-0073), the Hungarian Scientific Research Fund (OTKA NF105758, NF100677), and the Hungarian Academy of Sciences (BO 00174/10/5). Whereas, the experimental work on acinar cells was supported by Medical Research Council Programme Grants G0700167 and MR/J002771/1 as well as a Medical Research Council Professorship for OHP (G19/22/2). The authors declare that the experiments performed by them using the above-mentioned sources comply with the current laws of the country in which they were performed. AB - There are many reviews of pancreatic acinar cell function and also of pancreatic duct function, but there is an almost total absence of synthetic reviews bringing the integrated functions of these two vitally and mutually interdependent cells together. This is what we have attempted to do in this chapter. In the first part, we review the normal integrated function of the acinar-ductal system, with particular emphasis on how regulation of one type of cell also influences the other cell type. In the second part, we review a range of pathological processes, particularly those involved in acute pancreatitis (AP), an often-fatal human disease in which the pancreas digests itself, in order to explore how malfunction of one of the cell types adversely affects the function of the other. © Springer International Publishing Switzerland 2013. LA - English DB - MTMT ER - TY - JOUR AU - Lakatos, Petra AU - Szabó, Éva AU - Hegedűs, Csaba AU - Haskó, György AU - Gergely, Pál AU - Bay, Péter AU - Virág, László TI - 3-aminobenzamide protects primary human keratinocytes from UV-induced cell death by a poly(ADP-ribosyl)ation independent mechanism JF - BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH J2 - BBA-MOL CELL RES VL - 1833 PY - 2013 IS - 3 SP - 743 EP - 751 PG - 9 SN - 0167-4889 DO - 10.1016/j.bbamcr.2012.12.003 UR - https://m2.mtmt.hu/api/publication/2134503 ID - 2134503 N1 - Funding Agency and Grant Number: OTKA [K73003, K60780, K82009]; TAMOP [4.2.2-08/1-2008-0019, 4.2.1./B-09/1/KONV-2010-0007, 4.2.2.A-111/1/KONV-2012-0025] Funding text: This work was supported by the following grants OTKA (K73003, K60780, K82009) and TAMOP (4.2.2-08/1-2008-0019; 4.2.1./B-09/1/KONV-2010-0007 and 4.2.2.A-111/1/KONV-2012-0025). LA - English DB - MTMT ER - TY - JOUR AU - Bay, Péter AU - Hegedűs, Csaba AU - Szabó, Éva AU - Gyüre, L AU - Bakondi, Edina AU - Brunyánszki, Attila AU - Gergely, Szabolcs Gábor AU - Szabó, C AU - Virág, László TI - Poly(ADP-ribose) polymerase mediates inflammation in mouse model of contact hypersensitivity JF - JOURNAL OF INVESTIGATIVE DERMATOLOGY J2 - J INVEST DERMATOL VL - 129 PY - 2009 IS - 1 SP - 234 EP - 238 PG - 5 SN - 0022-202X DO - 10.1038/jid.2008.196 UR - https://m2.mtmt.hu/api/publication/236683 ID - 236683 LA - English DB - MTMT ER - TY - JOUR AU - Bay, Péter AU - Hegedűs, Csaba AU - Erdélyi, Katalin AU - Szabó, Éva AU - Bakondi, Edina AU - Gergely, Szabolcs Gábor AU - Szabo, C AU - Virág, László TI - Protein tyrosine nitration and poly(ADP-ribose) polymerase activation in N-methyl-N-nitro-N-nitrosoguanidine-treated thymocytes: Implication for cytotoxicity JF - TOXICOLOGY LETTERS J2 - TOXICOL LETT VL - 170 PY - 2007 IS - 3 SP - 203 EP - 213 PG - 11 SN - 0378-4274 DO - 10.1016/j.toxlet.2007.03.007 UR - https://m2.mtmt.hu/api/publication/1123898 ID - 1123898 AB - 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) is a DNA alkylating agent. DNA alkylation by MNNG is known to trigger accelerated poly(ADP-ribose) metabolism. Various nitroso compounds release nitric oxide (NO). Therefore, we set out to investigate whether MNNG functions as NO donor and whether MNNG-derived NO or secondary NO metabolites such as peroxynitrite contribute to MNNG-induced cytotoxicity. MNNG in aqueous solutions resulted in time- and concentration-dependent NO release and nitrite/nitrate formation. Moreover, various proteins in MNNG-treated thymocytes were found to be nitrated, indicating that MNNG-derived NO may combine with cellular superoxide to form peroxynitrite, a nitrating agent. MNNG also caused DNA breakage and increased poly (ADP-ribose) polymerase activity and cytotoxicity in thymocytes. MNNG-induced DNA damage (measured by the comet assay) and thymocyte death (measured by propidium iodide uptake) was prevented by the PARP inhibitor PJ-34 and by glutathione (GSH) or N-acetyleysteine (NAC). The cytoprotection provided by PJ-34 against necrotic parameters was paralleled by increased outputs in apoptotic parameters (caspase activity, DNA laddering) indicating that PARP activation diverts apoptotic death toward necrosis. As MNNG-induced cytotoxicity showed many similarities to peroxynitrite-induced cell death, we tested whether peroxynitrite was responsible for at least part of the cytotoxicity induced by MNNG. Cell-permeable enzymic antioxidants (superoxide dismutase and catalase), the NO scavenger cPTIO or the peroxynitrite decomposition catalyst FP15 failed to inhibit MNNG-induced DNA breakage and cytotoxicity. In conclusion, MNNG induces tyrosine nitration in thymocytes. Furthermore, MNNG damages DNA by a radical mechanism that does not involve NO or peroxynitrite. LA - English DB - MTMT ER - TY - JOUR AU - Hauser, Balázs AU - Bracht, H AU - Matejovic, M AU - Radermacher, P AU - Venkatesh, B TI - Nitric oxide synthase inhibition in sepsis? Lessons learned from large-animal studies. JF - ANESTHESIA AND ANALGESIA J2 - ANESTH ANALG VL - 101 PY - 2005 IS - 2 SP - 488 EP - 498 PG - 11 SN - 0003-2999 DO - 10.1213/01.ANE.0000177117.80058.4D UR - https://m2.mtmt.hu/api/publication/1700577 ID - 1700577 N1 - WoS:hiba:000230739100034 2020-08-27 02:04 DOI azonosító nem egyezik AB - Nitric Oxide (NO) plays a controversial role in the pathophysiology of sepsis and septic shock. Its vasodilatory effects are well known, but it also has pro- and antiinflammatory properties, assumes crucial importance in antimicrobial host defense, may act as an oxidant as well as an antioxidant, and is said to be a "vital poison" for the immune and inflammatory network. Large amounts of NO and peroxynitrite are responsible for hypotension, vasoplegia, cellular suffocation, apoptosis, lactic acidosis, and ultimately multiorgan failure. Therefore, NO synthase (NOS) inhibitors were developed to reverse the deleterious effects of NO. Studies using these compounds have not met with uniform success however, and a trial using the nonselective NOS inhibitor N(G)-methyl-l-arginine hydrochloride was terminated prematurely because of increased mortality in the treatment arm despite improved shock resolution. Thus, the issue of NOS inhibition in sepsis remains a matter of debate. Several publications have emphasized the differences concerning clinical applicability of data obtained from unresuscitated, hypodynamic rodent models using a pretreatment approach versus resuscitated, hyperdynamic models in high-order species using posttreatment approaches. Therefore, the present review focuses on clinically relevant large-animal studies of endotoxin or living bacteria-induced, hyperdynamic models of sepsis that integrate standard day-to-day care resuscitative measures. LA - English DB - MTMT ER - TY - JOUR AU - Virág, László AU - Szabó, Éva AU - Gergely, Pál AU - Szabó, Csaba TI - Peroxynitrite-induced cytotoxicity: mechanism and opportunities for intervention JF - TOXICOLOGY LETTERS J2 - TOXICOL LETT VL - 140-141 PY - 2003 SP - 113 EP - 124 PG - 12 SN - 0378-4274 DO - 10.1016/S0378-4274(02)00508-8 UR - https://m2.mtmt.hu/api/publication/101464 ID - 101464 N1 - Chemicals/CAS: 2 (2 amino 3 methoxyphenyl)chromone, 167869-21-8; 2 morpholino 8 phenylchromone, 154447-36-6; acidic fibroblast growth factor, 106096-92-8; adenosine diphosphate ribose, 20762-30-5; epidermal growth factor, 62229-50-9; morphine, 52-26-6, 57-27-2; nerve growth factor, 9061-61-4; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase, 58319-92-9; protein bcl 2, 219306-68-0; wortmannin, 19545-26-7; Peroxynitrous Acid, 14691-52-2; Poly(ADP-ribose) Polymerases, EC 2.4.2.30 Tradenames: ly 294002; pd 98059 WoS:hiba:000182307900014 2020-09-03 10:51 kötet nem egyezik LA - English DB - MTMT ER -