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1.

001-es BibID:BIBFORM045939
035-os BibID:PMID:12839568
Első szerző:Bakondi Edina (biokémikus, vegyész)
Cím:Role of Intracellular Calcium Mobilization and Cell-Density-Dependent Signaling in Oxidative-Stress-Induced Cytotoxicity in HaCaT Keratinocytes / Edina Bakondi, Mónika Gönczi, Éva Szabó, Péter Bai, Pál Pacher, Pál Gergely, László Kovács, János Hunyadi, Csaba Szabó, László Csernoch, László Virág
Dátum:2003
ISSN:0022-202X
Megjegyzések:Peroxynitrite is a nitric-oxide-derived cytotoxic mediator produced in a broad range of inflammatory conditions, ranging from sunburn erythema to contact hypersensitivity. Our previous work has shown that in HaCaT cells the cytotoxic activity of peroxynitrite involves both apoptotic and necrotic routes with poly(ADP-ribose) polymerase activation serving as a mol-ecular switch diverting the default apoptotic pathway toward necrosis. Nonetheless, keratinocytes are regarded as highly resistant toward environmental noxa including oxidative stress. We set out to investigate the possible role of two parameters, intracellular calcium mobilization and high cell density, in protecting HaCaT cells from peroxynitrite/oxidative-stress-induced cytotoxicity. First we characterized the effect of peroxynitrite on the calcium homeostasis of HaCaT cells and demonstrated that both authentic peroxynitrite and the peroxynitrite generating compound 3-morpholino-sydnonimine triggered an elevation in intracellular calcium levels. Moreover, we established that treatment of cells with the cell-permeable calcium chelator BAPTA-AM provided significant cytoprotection against peroxynitrite- and hydrogen-peroxide-induced cytotoxicity. Furthermore, when cells reached confluence they were highly resistant to the toxic effects of peroxynitrite, hydrogen peroxide, and superoxide. The resistance to oxidative stress provided by calcium chelation and high cell density involved inhibiting the activation of both poly(ADP-ribose) polymerase and caspases. Our data may provide an explanation for the resistance to oxidative stress of superficial, highly differentiated keratinocytes and indicate that basal proliferative keratinocytes are sensitive in vivo targets of oxidative stress injury.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Journal of Investigative Dermatology. - 121 : 1 (2003), p. 88-95. -
További szerzők:Gönczi Mónika (1974-) (élettanász) Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Bai Péter (1976-) (biokémikus) Pacher Pál Gergely Pál (1947-) (biokémikus) Kovács László (1939-) (élettanász) Hunyadi János (1943-) (bőrgyógyász, kozmetológus, allergológus) Szabó Csaba (1967-) (orvos) Csernoch László (1961-) (élettanász) Virág László (1965-) (biokémikus, sejtbiológus, farmakológus)
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2.

001-es BibID:BIBFORM014262
Első szerző:Pacher Pál
Cím:The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes / Pacher, P., Liaudet, L., Soriano, F. G., Mabley, J. G., Szabo, E., Szabo, C.
Dátum:2002
ISSN:0012-1797 (Print)
Megjegyzések:Patients with diabetes exhibit a high incidence of diabetic cardiomyopathy and vascular complications, which underlie the development of retinopathy, nephropathy, and neuropathy and increase the risk of hypertension, stroke, and myocardial infarction. There is emerging evidence that the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) importantly contributes to the development of endothelial dysfunction in a streptozotocin-induced model of diabetes. We investigated the role of PARP activation in the pathogenesis of cardiac dysfunction in streptozotocin-induced and genetic (nonobese diabetic) models of diabetes in rats and mice. Development of diabetes was accompanied by hyperglycemia, cardiac PARP activation, a selective loss of endothelium-dependent vasodilation in the thoracic aorta, and an early diastolic dysfunction of the heart. Treatment with a novel potent phenanthridinone-based PARP inhibitor, PJ34, starting 1 week after the onset of diabetes, restored normal vascular responsiveness and significantly improved cardiac dysfunction, despite the persistence of severe hyperglycemia. The beneficial effect of PARP inhibition persisted even after several weeks of discontinuation of the treatment. Thus, PARP activation plays a central role in the pathogenesis of diabetic cardiovascular (cardiac as well as endothelial) dysfunction. PARP inhibitors may exert beneficial effects against the development of cardiovascular complications in diabetes.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Animals
külföldön készült közlemény
Diabetes Mellitus/genetics/*physiopathology
Diabetes Mellitus, Experimental/physiopathology
Endothelium, Vascular/*physiopathology
Enzyme Activation/physiology
Female
Heart/*physiopathology
Male
Mice
Mice, Inbred NOD
Myocardium/enzymology
Poly(ADP-ribose) Polymerases/*metabolism/physiology
Rats
Rats, Wistar
Ventricular Function
Megjelenés:Diabetes. - 51 : 2 (2002), p. 514-521. -
További szerzők:Liaudet, Lucas Soriano, Francisco Garcia Mabley, Jon G. Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Szabó Csaba
Internet cím:elektronikus változat
DOI
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3.

001-es BibID:BIBFORM014261
Első szerző:Pacher Pál
Cím:Potent metalloporphyrin peroxynitrite decomposition catalyst protects against the development of doxorubicin-induced cardiac dysfunction / Pacher, P., Liaudet, L., Bai, P., Mabley, J. G., Kaminski, P. M., Virag, L., Deb, A., Szabo, E., Ungvari, Z., Wolin, M. S., Groves, J. T., Szabo, C.
Dátum:2003
ISSN:1524-4539 (Electronic)
Megjegyzések:Increased oxidative stress and dysregulation of nitric oxide have been implicated in the cardiotoxicity of doxorubicin (DOX), a commonly used antitumor agent. Peroxynitrite is a reactive oxidant produced from nitric oxide and superoxide in various forms of cardiac injury. Using a novel metalloporphyrinic peroxynitrite decomposition catalyst, FP15, and nitric oxide synthase inhibitors or knockout mice, we now delineate the pathogenetic role of peroxynitrite in rodent models of DOX-induced cardiac dysfunction. METHODS AND RESULTS: Mice received a single injection of DOX (25 mg/kg IP). Five days after DOX administration, left ventricular performance was significantly depressed, and high mortality was noted. Treatment with FP15 and an inducible nitric oxide synthase inhibitor, aminoguanidine, reduced DOX-induced mortality and improved cardiac function. Genetic deletion of the inducible nitric oxide synthase gene was also accompanied by better preservation of cardiac performance. In contrast, inhibition of the endothelial isoform of nitric oxide synthase with N-nitro-L-arginine methyl ester increased DOX-induced mortality. FP15 reduced the DOX-induced increase in serum LDH and creatine kinase activities. Furthermore, FP15 prevented the DOX-induced increase in lipid peroxidation, nitrotyrosine formation, and metalloproteinase activation in the heart but not NAD(P)H-driven superoxide generation. Peroxynitrite neutralization did not interfere with the antitumor effect of DOX. FP15 also decreased ischemic injury in rats and improved cardiac function and survival of mice in a chronic model of DOX-induced cardiotoxicity. CONCLUSIONS: Thus, peroxynitrite plays a key role in the pathogenesis of DOX-induced cardiac failure. Targeting peroxynitrite formation may represent a new cardioprotective strategy after DOX exposure or in other conditions associated with peroxynitrite formation, including myocardial ischemia/reperfusion injury.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Acute Disease
Animals
Catalysis/drug effects
külföldön készült közlemény
Chronic Disease
Creatine Kinase/blood
Disease Models, Animal
Doxorubicin/*toxicity
Enzyme Inhibitors/pharmacology
Heart/*drug effects/physiopathology
Heart Failure/*chemically induced/physiopathology/prevention & control
L-Lactate Dehydrogenase/blood
Male
Metalloporphyrins/*pharmacology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Nitric Oxide Synthase/antagonists & inhibitors/genetics/metabolism
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Oxidative Stress/drug effects/genetics
Peroxynitrous Acid/*metabolism
Survival Rate
Megjelenés:Circulation. - 107 : 6 (2003), p. 896-904. -
További szerzők:Liaudet, Lucas Bai Péter (1976-) (biokémikus) Mabley, Jon G. Kaminski, Pawel M. Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Deb, Amitabha Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Ungvári Zoltán Wolin, Michael S. Groves, John T. Szabó Csaba
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4.

001-es BibID:BIBFORM014263
Első szerző:Soriano, Francisco Garcia
Cím:Resistance to acute septic peritonitis in poly(ADP-ribose) polymerase-1-deficient mice / Soriano, F. G., Liaudet, L., Szabo, E., Virag, L., Mabley, J. G., Pacher, P., Szabo, C.
Dátum:2002
ISSN:1073-2322 (Print)
Megjegyzések:Sepsis is associated with a widespread production of proinflammatory cytokines and various oxidant species. Activation of the enzyme poly(ADP-ribose) polymerase (PARP) has been shown to contribute to cell necrosis and organ failure in various diseases associated with inflammation and reperfusion injury. The aim of the current study was to elucidate the role of PARP activation in the multiple organ dysfunction complicating sepsis in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Mice genetically deficient in PARP (PARP-/-) and their wild-type littermates (PARP+/+) were subjected to CLP. After 12 and 24 h, the proinflammatory cytokines TNF-alpha and IL-6, as well as the anti-inflammatory cytokine IL-10, and nitrite/nitrate were measured in plasma samples. Organs were harvested for the measurement of myeloperoxidase (MPO) and malondialdehyde (MDA) levels, and immunohistochemical staining for nitrotyrosine and poly(ADP ribose) was performed in gut sections. PARP-/- mice, and their wild-type littermate showed a similar time-dependent increase in plasma nitrite/nitrate and in gut and lung MDA content, as well as the presence of nitrotyrosine in the gut. In contrast to wild-type mice showing a PARP activation in the gut, PARP-/- mice had no staining for poly(ADP ribose). PARP-/- mice had significantly lower plasma levels of TNF-alpha, IL-6, and IL-10, and they exhibited a reduced degree of organ inflammation, indicated by decreased MPO activity in the gut and lung. These effects were associated with a significant improvement in the survival of CLP in PARP-/- mice. Thus, PARP activation has an important role in systemic inflammation and organ damage in the present model of polymicrobial septic shock.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Acute Disease
egyetemen (Magyarországon) készült közlemény
Animals
Cytokines
Enzyme Activation
Inflammation Mediators
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Multiple Organ Failure
Peritonitis
Peroxidase/metabolism
Poly(ADP-ribose) Polymerases
Sepsis
Megjelenés:Shock. - 17 : 4 (2002), p. 286-292. -
További szerzők:Liaudet, Lucas Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Mabley, Jon G. Pacher Pál Szabó Csaba
Internet cím:elektronikus változat
DOI
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