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1.

001-es BibID:BIBFORM014283
Első szerző:Bai Péter (biokémikus)
Cím:Partial protection by poly(ADP-ribose) polymerase inhibitors from nitroxyl-induced cytotoxity in thymocytes / Bai Péter, Bakondi Edina, Szabó Éva, Gergely Pál, Szabo Csaba, Virág László
Dátum:2001
ISSN:0891-5849 (Print)
Megjegyzések:Nitroxyl (NO(-)/HNO), has been proposed to be one of the NO(*)-derived cytotoxic species. Although the biological effect of nitroxyl is largely unknown, it has been reported to cause DNA breakage and cytotoxicity. We have therefore investigated whether NO(-)/HNO-induced DNA single-strand breakage activates the nuclear nick sensor enzyme poly(ADP-ribose) polymerase (PARP) and whether PARP activation affects the mode of NO(-)/HNO- induced cell death. NO(-)/HNO generated from Angeli's salt (AS, sodium trioxodinitrate) (0-300 microM) induced DNA single-strand breakage, PARP activation, and a concentration-dependent cytotoxicity in murine thymocytes. AS-induced cell death was also accompanied by decreased mitochondrial membrane potential and increased secondary superoxide production. The cytotoxicity of AS, as measured by propidium iodide uptake, was abolished by electron acceptors potassium ferricyanide, TEMPOL, the intracellular calcium chelator BAPTA-AM, and by PARP inhibitors 3-aminobenzamide (3-AB) and PJ-34. The cytoprotective effect of 3-AB was paralleled by increased output of AS-induced apoptotic parameters such as phosphatidylserine exposure, caspase activation, and DNA fragmentation. No significant increase in tyrosine nitration could be observed in AS-treated thymocytes as opposed to peroxynitrite-treated cells, indicating that tyrosine nitration is not likely to contribute to NO(-)/HNO-induced cytotoxicity. Our results demonstrate that NO(-)/HNO-induced PARP activation shifts the default apoptotic cell death toward necrosis in thymocytes. However, as total PARP inhibition resulted only in 30% cytoprotection, PARP-independent mechanisms dominate NO(-)/HNO-induced cytotoxicity in thymocytes.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Animals
egyetemen (Magyarországon) készült közlemény
Apoptosis
Benzamides/ pharmacology
Caspases/metabolism
Cells, Cultured
DNA Damage/drug effects
DNA Fragmentation/drug effects
Enzyme Activation/drug effects/physiology
Enzyme Inhibitors/ pharmacology
Male
Mice
Mice, Inbred C57BL
Mitochondria/ drug effects
Nitrates
Nitrites/toxicity
Nitrogen Oxides/ toxicity
Poly(ADP-ribose) Polymerases/ antagonists & inhibitors/metabolism
Protective Agents/ pharmacology
Thymus Gland/cytology/ drug effects
Tyrosine
Megjelenés:Free radical biology and medicine. - 31 : 12 (2001), p. 1616-1623. -
További szerzők:Bakondi Edina (1975-) (biokémikus, vegyész) Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Gergely Pál (1947-) (biokémikus) Szabó Csaba Virág László (1965-) (biokémikus, sejtbiológus, farmakológus)
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2.

001-es BibID:BIBFORM004100
Első szerző:Bai Péter (biokémikus)
Cím:Poly(ADP-ribose) polymerase mediates inflammation in a mouse model of contact hypersensitivity / Bai P., Hegedűs C., Szabó É., Gyüre L., Bakondi E., Brunyánszki A., Gergely Sz., Szabó C., Virág L.
Dátum:2009
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
poly(ADP-ribose) polymerase
cytokine
allergy
matrix metalloproteinase
tissue inhibitors of metalloproteinases
egyetemen (Magyarországon) készült közlemény
Megjelenés:The Journal of Investigative Dermatology. - 129 : 1 (2009), p. 234-238. -
További szerzők:Hegedűs Csaba (1980-) (biokémikus, molekuláris biológus) Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Gyüre László Bakondi Edina (1975-) (biokémikus, vegyész) Brunyánszki Attila (1980-) (biológus, biotechnológus) Gergely Szabolcs (1977-) (kardiológus) Szabó Csaba Virág László (1965-) (biokémikus, sejtbiológus, farmakológus)
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3.

001-es BibID:BIBFORM001037
Első szerző:Bai Péter (biokémikus)
Cím:Protein tyrosine nitration and poly(ADP-ribose) polymerase activation in N-methyl-N-nitrosoguanidine-treated thymocytes : implication for cytotoxicity / Bai P., Hegedűs C., Erdélyi K., Szabó E., Bakondi E., Gergely S., Szabó C., Virág L.
Dátum:2007
Megjegyzések: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-acetylcysteine (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.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
1-methyl-3-nitro-1-nitrosoguanidine
peroxynitrite
egyetemen (Magyarországon) készült közlemény
poly(ADP-ribose) polymerase
necrosis
apoptosis
nitric oxide
Megjelenés:Toxicology Letters 170 : 3 (2007), p. 203-213. -
További szerzők:Hegedűs Csaba (1980-) (biokémikus, molekuláris biológus) Erdélyi Katalin (1978-) (molekuláris biológus, biokémikus) Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Bakondi Edina (1975-) (biokémikus, vegyész) Gergely Szabolcs (1977-) (kardiológus) Szabó Csaba Virág László (1965-) (biokémikus, sejtbiológus, farmakológus)
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4.

001-es BibID:BIBFORM014256
Első szerző:Bakondi Edina (biokémikus, vegyész)
Cím:Detection of poly(ADP-ribose) polymerase activation in oxidatively stressed cells and tissues using biotinylated NAD substrate / Bakondi, E., Bai, P., Szabo, E., Hunyadi, J., Gergely, P., Szabo, C., Virag, L.
Dátum:2002
ISSN:0022-1554 (Print)
Megjegyzések:Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme activated by DNA damage. Activated PARP cleaves NAD(+) into nicotinamide and (ADP-ribose) and polymerizes the latter on nuclear acceptor proteins. Over-activation of PARP by reactive oxygen and nitrogen intermediates represents a pathogenetic factor in various forms of inflammation, shock, and reperfusion injury. Using a novel commercially available substrate, 6-biotin-17-nicotinamide-adenine-dinucleotide (bio-NAD(+)), we have developed three applications, enzyme cytochemistry, enzyme histochemistry, and cell ELISA, to detect the activation of PARP in oxidatively stressed cells and tissues. With the novel assay we were able to detect basal and hydrogen peroxide-induced PARP activity in J774 macrophages. We also observed that mitotic cells display remarkably elevated PARP activity. Hydrogen peroxide-induced PARP activation could also be detected in wild-type peritoneal macrophages but not in macrophages from PARP-deficient mice. Application of hydrogen peroxide to the skin of mice also induced bio-NAD(+) incorporation in the keratinocyte nuclei. Hydrogen peroxide-induced PARP activation and its inhibition by pharmacological PARP inhibitors could be detected in J774 cells with the ELISA assay that showed good correlation with the traditional [(3)H]-NAD incorporation method. The bio-NAD(+) assays represent sensitive, specific, and non-radioactive alternatives for detection of PARP activation.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Animals
Biotin/analogs & derivatives
Cells, Cultured
egyetemen (Magyarországon) készült közlemény
Enzyme Activation
Enzyme-Linked Immunosorbent Assay
Hydrogen Peroxide
Macrophages
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
NAD/analogs & derivatives
Oxidative Stress
Poly(ADP-ribose) Polymerases
Skin/drug effects
Megjelenés:The Journal of Histochemistry and Cytochemistry. - 50 : 1 (2002), p. 91-98. -
További szerzők:Bai Péter (1976-) (biokémikus) Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Hunyadi János (1943-) (bőrgyógyász, kozmetológus, allergológus) Gergely Pál (1947-) (biokémikus) Szabó Csaba Virág László (1965-) (biokémikus, sejtbiológus, farmakológus)
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DOI
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5.

001-es BibID:BIBFORM007444
Első szerző:Erdélyi Katalin (molekuláris biológus, biokémikus)
Cím:Dual role of poly(ADP-ribose) glycohydrolase in the regulation of cell death in oxidatively stressed A549 cells / Erdélyi K., Bai P., Kovács I., Szabó É., Mocsár G., Kakuk A., Szabó Cs., Gergely P., Virág L.
Dátum:2009
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
DNA damage
gene silencing
egyetemen (Magyarországon) készült közlemény
apoptosis
necrosis
hydrogen peroxide
apoptosis-inducing factor
Megjelenés:The FASEB Journal. - 23 : 10 (2009), p. 3553-3563. -
További szerzők:Bai Péter (1976-) (biokémikus) Kovács István (1985-) (biokémikus) Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Mocsár Gábor (1981-) (biofizikus) Kakuk Annamária (1976-) (molekuláris biológus) Szabó Csaba Gergely Pál (1947-) (biokémikus) Virág László (1965-) (biokémikus, sejtbiológus, farmakológus)
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6.

001-es BibID:BIBFORM014257
Első szerző:Faro, R.
Cím:Myocardial protection by PJ34, a novel potent poly (ADP-ribose) synthetase inhibitor / Faro, R., Toyoda, Y., McCully, J. D., Jagtap, P., Szabo, E., Virag, L., Bianchi, C., Levitsky, S., Szabo, C., Sellke, F. W.
Dátum:2002
ISSN:0003-4975 (Print)
Megjegyzések:The activation of poly (ADP-ribose) synthetase plays an important role in the pathogenesis leading to myocardial ischemia-reperfusion injury. The aim of this study was to determine if a novel potent inhibitor of poly (ADP-ribose) synthetase, PJ34, provides myocardial protection. METHODS: Pigs were subjected to 60 minutes of regional ischemia followed by 180 minutes of reperfusion. Ten mg/kg of PJ34 (PJ34; n = 6) was administrated intravenously (treated group) from 15 to 5 minutes before reperfusion followed by 3 mg/kg/hour of PJ34 from 5 minutes before reperfusion to the end of 180 minutes reperfusion. Control pigs (n = 7) received vehicle only. Arterial and left ventricular pressure and coronary flow were monitored. RESULTS: The PJ34 showed significant reduction on infarct size (37.5%+/-4.5% and 50.5%+/-4.8% of the area at risk) for PJ34 and control pigs groups, respectively, (p < 0.05). Significant reduction in postsystolic shortening, as well as improvement on segment shortening, and positive first derivative of pressure over time (+dP/dt) maximum were also observed in PJ34 versus control pigs (p < 0.05). CONCLUSIONS: Our results suggest that PJ34 provides cardioprotection by decreasing myocardial infarct size and enhancing postischemic regional and global functional recovery.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Animals
Blood Pressure
Coronary Circulation
Enzyme Inhibitors
Female
Hemodynamics
Male
Myocardial Contraction
Myocardial Infarction
Myocardial Reperfusion Injury
Myocardium
külföldön készült közlemény
Phenanthrenes
Poly(ADP-ribose) Polymerases
Swine
Megjelenés:The Annals of Thoracic Surgery. - 73 : 2 (2002), p. 575-581. -
További szerzők:Toyoda, Y. McCully, J. D. Jagtap, Prakash Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Bianchi, C. Levitsky, S. Szabó Csaba Sellke, F. W.
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7.

001-es BibID:BIBFORM014258
Első szerző:Goldfarb, R. D.
Cím:Protective effect of a novel, potent inhibitor of poly(adenosine 5'-diphosphate-ribose) synthetase in a porcine model of severe bacterial sepsis / Goldfarb, R. D., Marton, A., Szabo, E., Virag, L., Salzman, A. L., Glock, D., Akhter, I., McCarthy, R., Parrillo, J. E., Szabo, C.
Dátum:2002
ISSN:0090-3493 (Print)
Megjegyzések:To determine whether activation of the nuclear enzyme poly(adenosine 5'-diphosphate [ADP]-ribose) synthetase (PARS) contributes to mortality rate, myocardial dysfunction, and cardiovascular collapse in a porcine model of sepsis induced by implantation of an infected clot. DESIGN: Prospective, random animal study. SETTING: Research laboratory at Rush Presbyterian St. Luke's Medical Center. SUBJECTS: Twenty pigs were chronically instrumented with intracardiac transducers to measure left ventricular pressure, sonomicrometer crystals in the left ventricle to measure short axis diameter, an ultrasonic flow meter to measure cardiac output, and catheters in the pulmonary artery and aorta to measure blood pressures and collect samples. INTERVENTIONS: By using a randomized study design, we administered either the novel potent PARS inhibitor PJ34 (10 mg/kg for 1 hr, 2 mg x kg(-1) x hr(-1) for 96 hrs) or vehicle to pigs immediately before intraperitoneal implantation of Escherichia coli 0111.B4 (2.3 +/- 0.1 x 10(10) colony-forming units/kg)-laden fibrin clots to produce peritonitis and bacteremia. MEASUREMENTS AND MAIN RESULTS: In vehicle-treated pigs, 12% survival was recorded at 24 hrs, whereas 83% and 66% survival was recorded in the PJ34-treated animals at 24 and 96 hrs, respectively (p <.05). PJ34 treatment attenuated bacteremia-induced increases in systemic and pulmonary vascular resistances. In controls, peritonitis induced rapid increase in plasma tumor necrosis factor-alpha. PJ34 treatment significantly attenuated this cytokine response. The formation of peroxynitrite and the activation of PARS were confirmed in hearts and lungs of the septic pigs by the immunohistochemical detection of nitrotyrosine and poly(ADP-ribose), respectively. Inhibition of PARS with PJ34 abolished poly(ADP-ribose) formation in septic animals. CONCLUSIONS: Treatment with a potent PARS inhibitor improved survival and cardiovascular status and attenuated an important mediator component of the inflammatory response in a lethal porcine model of sepsis.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Animals
Bacterial Infections
Disease Models, Animal
Enzyme Inhibitors
Escherichia coli Infections
Hemodynamics
Peritonitis
Phenanthrenes
Poly(ADP-ribose) Polymerases
Prospective Studies
Random Allocation
Swine
Tumor Necrosis Factor-alpha
külföldön készült közlemény
Megjelenés:Critical care Medicine. - 30 : 5 (2002), p. 974-980. -
További szerzők:Marton, A. Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Salzman, Andrew L. Glock, D. Akhter, I. McCarthy, R. Parrillo, J. E. Szabó Csaba
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8.

001-es BibID:BIBFORM003552
Első szerző:Hegedűs Csaba (biokémikus, molekuláris biológus)
Cím:Protein kinase C protects from DNA damage-induced necrotic cell death by inhibiting poly(ADP-ribose) polymerase-1 / Hegedűs Cs., Lakatos P., Oláh G., Tóth B. I., Gergely Sz., Szabó É., Bíró T., Szabó Cs., Virág L.
Dátum:2008
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
poly(ADP-ribose) polymerase-1
protein kinase C
cytotoxicity
necrosis
apoptosis
1-methyl-3-nitro-1-nitrosoguanidine
egyetemen (Magyarországon) készült közlemény
Megjelenés:FEBS Letters. - 582 : 12 (2008), p. 1672-1678. -
További szerzők:Lakatos Petra (1985-) (Molekuláris biológus) Oláh Gábor Tóth István Balázs (1978-) (élettanász) Gergely Szabolcs (1977-) (kardiológus) Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Bíró Tamás (1968-) (élettanász) Szabó Csaba Virág László (1965-) (biokémikus, sejtbiológus, farmakológus)
Internet cím:elektronikus változat
DOI
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9.

001-es BibID:BIBFORM014259
Első szerző:Jagtap, Prakash
Cím:Novel phenanthridinone inhibitors of poly (adenosine 5'-diphosphate-ribose) synthetase: potent cytoprotective and antishock agents / Jagtap, P., Soriano, F. G., Virag, L., Liaudet, L., Mabley, J., Szabo, E., Hasko, G., Marton, A., Lorigados, C. B., Gallyas, F., Jr., Sumegi, B., Hoyt, D. G., Baloglu, E., VanDuzer, J., Salzman, A. L., Southan, G. J., Szabo, C.
Dátum:2002
ISSN:0090-3493 (Print)
Megjegyzések:To synthesize novel inhibitors of the nuclear enzyme poly(adenosine 5'-diphosphate [ADP]-ribose) synthetase (PARS), also known as poly(ADP-ribose) polymerase (PARP), and to test them in in vitro models of oxidant-induced cytotoxicity and in endotoxin and splanchnic occlusion-reperfusion-induced shock. DESIGN: Randomized, prospective laboratory study. SETTING: Research laboratory. SUBJECTS: Murine macrophages, thymocytes, and endothelial cells; Balb/c mice and Wistar rats. INTERVENTIONS: Macrophages and endothelial cells were treated with peroxynitrite and bleomycin to induce PARS activation, and thymocytes were treated with peroxynitrite to induce cell necrosis. Novel PARS inhibitors were synthesized and used to reduce PARS activation and to reverse cytotoxicity. Balb/c mice were subjected to splanchnic occlusion and reperfusion and were pretreated with various doses (1-10 mg/kg intraperitoneally) of PJ34, a selected, potent, water-soluble PARS inhibitor. The passage of fluorescein isothiocyanate-conjugated dextran (4 kDa) was analyzed in everted gut ileal sacs incubated ex vivo as an index of gut permeability. Wistar rats were subjected to Escherichia coli bacterial lipopolysaccharide (40 mg/kg intraperitoneally). PJ34 was also used at 10 mg/kg intraperitoneally, 1 hr before lipopolysaccharide or at 25 mg/kg intraperitoneally 1 hr after lipopolysaccharide treatment. Serum concentrations of indicators or multiple organ injury, concentrations of various proinflammatory mediators, and tissue concentrations of myeloperoxidase and malondialdehyde were measured. In addition, survival rates and vascular contractile and relaxant responses were recorded. MEASUREMENTS AND MAIN RESULTS: Appropriate modifications of the phenanthridinone core structure yielded significant increases in the potency of the compounds, both as PARS inhibitors and as cytoprotective agents. The compound N-(6-oxo-5,6-dihydro-phenanthridin-2-yl) -N,N-dimethylacetamide (designated as PJ34) was one of the potent PARS inhibitors of the series, and it dose-dependently protected against thymocyte necrosis, with a half-maximal restoration of cell viability of 35 nM and complete protection at 200 nM. PARS activation also was visualized by immunohistochemistry and was dose-dependently suppressed by PJ34. The effect of PJ34 was dose-dependently reversed by excess nicotinamide adenine dinucleotide (oxidized). The PARS inhibitors dose-dependently suppressed proinflammatory cytokine and chemokine production and restored viability in immunostimulated macrophages. PJ34 was selected for the subsequent in vivo studies. PJ34 significantly protected against splanchnic reperfusion-induced intestinal hyperpermeability in the mouse. PJ34 reduced peak plasma concentrations of tumor necrosis factor-alpha, interleukin-1beta, and nitrite/nitrate in the plasma of lipopolysaccharide-treated rats. PJ34 ameliorated the lipopolysaccharide-induced increases in indexes of liver and kidney failure and concentrations of myeloperoxidase and malondialdehyde in the lung and gut. Lipopolysaccharide elicited vascular dysfunction, which was normalized by PJ34. Lipopolysaccharide-induced mortality was reduced by PJ34 (both pre- and posttreatment). CONCLUSIONS: The novel series of phenanthridinone PARS inhibitors have potent cytoprotective effects in vitro and significant protective effects in shock and reperfusion injury in rodent models in vivo.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Animals
Bleomycin/pharmacology
Cells, Cultured
*Cytoprotection
Dose-Response Relationship, Drug
Enzyme Activation
Enzyme Inhibitors/*pharmacology
külföldön készült közlemény
Interleukin-1/blood
Kidney/chemistry
Lipopolysaccharides/pharmacology
Lung/chemistry
Malondialdehyde/analysis
Mice
Mice, Inbred BALB C
Nitrates/blood
Nitrites/blood
Peroxidase/analysis
Peroxynitrous Acid/pharmacology
Phenanthrenes/*pharmacology
Poly(ADP-ribose) Polymerases/*antagonists & inhibitors
Rats
Rats, Wistar
Shock/*prevention & control
Tumor Necrosis Factor-alpha/analysis
Megjelenés:Critical Care Medicine. - 30 : 5 (2002), p. 1071-1082. -
További szerzők:Soriano, Francisco Garcia Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Liaudet, Lucas Mabley, Jon G. Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Haskó György (1967-) (biokémikus) Marton, A. Lorigados, Clara Batista Gallyas Ferenc Jr Sümegi Balázs Hoyt, Dale G. Baloglu, Erkan VanDuzer, John Salzman, Andrew L. Southan, Garry J. Szabó Csaba
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10.

001-es BibID:BIBFORM040005
Első szerző:Liaudet, Lucas
Cím:Suppression of poly (ADP-ribose) polymerase activation by 3-aminobenzamide in a rat model of myocardial infarction : long term morphological and functional consequences / Liaudet, L., Szabó, É., Timashpolsky, L., Virág, L., Cziráki, A., Szabó, C.
Dátum:2001
ISSN:0007-1188
Megjegyzések:1. Recent studies demonstrated that inhibition or genetic inactivation of the enzyme poly (ADP-ribose) polymerase (PARP) is beneficial in myocardial reperfusion injury. PARP activation in the reperfused myocardium has been assumed, but not directly demonstrated. Furthermore, the issue whether pharmacological PARP inhibition affords long-term functional benefit in the reperfused myocardium has not been explored. These questions were addressed in the present study. 2. In a rat model of myocardial ischemia (1 h) and reperfusion (up to 24 h), there was a marked and significant activation of PARP in the ischemic borderzone, as determined by poly(ADP-ribose) (PAR) immunohistochemistry. PAR localized to the nuclei of myocytes and infiltrating mononuclear cells. In the core of the infarction, necrotic tissues and diffuse PAR staining were observed. PARP activation remained markedly detectable 24 h after reperfusion. The PARP inhibitor 3-aminobenzamide (20 mg kg(-1) intraperitoneally 10 min before reperfusion, and every 2 h thereafter for 6 h) markedly reduced the activation of the enzyme in myocytes. 3. 3-aminobenzamide significantly protected against myocardial morphological and functional alterations at 24 h post-reperfusion. Notably, infarct size was reduced, circulating creatine kinase activity was attenuated, and myocardial contractility (dP dt(-1)) was restored by 3-aminobenzamide. 4. Our results demonstrate a significant and prolonged activation of PARP in the reperfused myocardium, localizing to the necrotic area and the ischaemic borderzone. Furthermore, the studies demonstrate that PARP inhibition affords long-term beneficial morphological and functional effects in the reperfused myocardium. These data strengthen the notion that pharmacological PARP inhibition is a viable novel experimental approach for protection against myocardial reperfusion injury.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:British Journal Of Pharmacology. - 133 : 8 (2001), p. 1424-1430. -
További szerzők:Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Timashpolsky, Leonid Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Cziráki Attila Szabó Csaba
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DOI
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11.

001-es BibID:BIBFORM014260
Első szerző:Liaudet, Lucas
Cím:Protection against hemorrhagic shock in mice genetically deficient in poly(ADP-ribose)polymerase / Liaudet, L., Soriano, F. G., Szabo, E., Virag, L., Mabley, J. G., Salzman, A. L., Szabo, C.
Dátum:2000
ISSN:0027-8424 (Print)
Megjegyzések:Hemorrhagic shock (HS) and resuscitation leads to widespread production of oxidant species. Activation of the enzyme poly(ADP-ribose) polymerase (PARP) has been shown to contribute to cell necrosis and organ failure in various disease conditions associated with oxidative stress. We tested the hypothesis whether PARP activation plays a role in the multiple organ dysfunction complicating HS and resuscitation in a murine model of HS and resuscitation by using mice genetically deficient in PARP (PARP(-/-)) and their wild-type littermates (PARP(+/+)). Animals were bled to a mean blood pressure of 45 mmHg (1 mmHg = 133 Pa) and resuscitated after 45 min with isotonic saline (2x volume of shed blood). There was a massive activation of PARP, detected by poly(ADP-ribose) immunohistochemistry, which localized to the areas of the most severe intestinal injury, i.e., the necrotic epithelial cells at the tip of the intestinal villi, and colocalized with tyrosine nitration, an index of peroxynitrite generation. Intestinal PARP activation resulted in gut hyperpermeability, which developed in PARP(+/+) but not PARP(-/-) mice. PARP(-/-) mice were also protected from the rapid decrease in blood pressure after resuscitation and showed an increased survival time, as well as reduced lung neutrophil sequestration. The beneficial effects of PARP suppression were not related to a modulation of the NO pathway nor to a modulation of signaling through IL-6, which similarly increased in both PARP(+/+) and PARP(-/-) mice exposed to HS. We propose that PARP activation and associated cell injury (necrosis) plays a crucial role in the intestinal injury, cardiovascular failure, and multiple organ damage associated with resuscitated HS.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Acetylcholine/pharmacology
külföldön készült közlemény
Animals
Aorta, Thoracic/drug effects/physiology/physiopathology
Blood Pressure
Blood Volume
Dinoprost/pharmacology
Enzyme Activation
*Hemodynamics
Intestinal Mucosa/enzymology/*pathology
Liver/enzymology/pathology
Male
Mice
Mice, Knockout
Muscle Contraction/drug effects
Muscle Relaxation/drug effects
Muscle, Smooth, Vascular/drug effects/physiology/*physiopathology
Peroxidase/metabolism
Poly(ADP-ribose) Polymerases/deficiency/genetics/*metabolism
Resuscitation
Shock, Hemorrhagic/*genetics/physiopathology/therapy
Sodium Chloride/therapeutic use
Tyrosine/analogs & derivatives/metabolism
Megjelenés:Proceedings of the National Academy of Sciences of the United States of America. - 97 : 18 (2000), p. 10203-10208. -
További szerzők:Soriano, Francisco Garcia Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Mabley, Jon G. Salzman, Andrew L. Szabó Csaba
Internet cím:DOI
elektronikus változat
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12.

001-es BibID:BIBFORM040009
Első szerző:Mabley, Jon G.
Cím:Anti-inflammatory effects of a novel, potent inhibitor of poly (ADP-ribose) polymerase / Mabley, J. G., Jagtap, P., Perretti, M., Getting, S. J., Salzman, A. L., Virág, L., Szabó, É., Soriano, F. G., Liaudet, L., Abdelkarim, G. E., Haskó, G., Marton, A., Southan, G. J., Szabó, C.
Dátum:2001
ISSN:1023-3830
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Inflammation Research. - 50 : 11 (2001), p. 561-569. -
További szerzők:Jagtap, Prakash Perretti, Mauro Getting, S. J. Salzman, Andrew L. Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Soriano, Francisco Garcia Liaudet, Lucas Abdelkarim, G. Haskó György (1967-) (biokémikus) Marton, A. Southan, Garry J. Szabó Csaba
Internet cím:Szerző által megadott URL
DOI
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