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001-es BibID:BIBFORM014289
Első szerző:Virág László (biokémikus, sejtbiológus, farmakológus)
Cím:Effects of poly(ADP-ribose) polymerase inhibition on inflammatory cell migration in a murine model of asthma / Virag, L., Bai, P., Bak, I., Pacher, P., Mabley, J. G., Liaudet, L., Bakondi, E., Gergely, P., Kollai, M., Szabo, C.
ISSN:0891-5849 (Print)
Megjegyzések:Poly(ADP-ribose) polymerase-1 (PARP-1), a monomeric nuclear enzyme present in eukaryotes, plays a role in cell death, inflammatory mediator expression, and mononuclear cell recruitment in various experimental models of inflammation and reperfusion injury. Part of the molecular mechanism of this function involves the regulation of cytokine and chemokine production. Since chemokines are principal regulators of mononuclear and polymorphonuclear cell trafficking in asthma, we investigated the possibility whether PARP modulates chemokine production and cell recruitment in a murine model of asthma. MATERIAL/METHODS: We studied ovalbumin-sensitized mice challenged with a single dose of ovalbumin. RESULTS: PARP inhibition with the phenanthridinone-based PARP inhibitor PJ34 suppressed inflammatory cell migration. These effects were associated with downregulation of the CC chemokine MIP-1alpha, but not the CXC chemokine MIP-2. The production of TNF- alpha and IL-12, but not IL-5 or IL-13, was also suppressed by PARP inhibition. CONCLUSIONS: Our results demonstrate the pathogenetic role of PARP activation in a murine model of asthma. PARP selectively regulates the production of certain chemokines and cytokines in this experimental model, which may be responsible for some of the observed protective effects seen in the current murine asthma model.Matrix metalloproteinase (MMP) activation contributes to the development of various pathophysiological conditions, including dilated cardiomyopathy, congestive heart failure, and reperfusion injury. Increased oxidative and nitrosative stress have been implicated in the activation of MMPs and also in the cardiotoxicity of doxorubicin (DOX), a commonly used antitumor agent. Thus, we hypothesized that MMP activation occurs in DOX-induced cardiotoxicity. Male Balb/c mice received a single injection of DOX (25 mg/kg i.p.) and were sacrificed 12 h, 1, 2, 3 and 4 days later. Hearts and aortae were harvested for MMP zymography. DOX induced time-dependent activation of MMPs both in the heart and in the aortic tissue with an earlier onset in the latter. These results demonstrate that MMP activation is an early event in DOX-induced cardiotoxicity and raises the possibility that MMP inhibitors may influence the outcome of this severe complication.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Asthma/ drug therapy
Bronchoalveolar Lavage
Cell Death
Cell Movement
Chemokine CXCL2
Disease Models, Animal
Enzyme Inhibitors/ pharmacology
Leukocytes, Mononuclear/metabolism
Mice, Inbred BALB C
Poly(ADP-ribose) Polymerases/ antagonists & inhibitors
Time Factors
Tumor Necrosis Factor-alpha/metabolism
Antineoplastic Agents/toxicity
Biological Markers/analysis
Cardiomyopathy, Dilated/chemically induced/enzymology
Doxorubicin/ toxicity
Enzyme Activation
Heart/ drug effects
Heart Failure/chemically induced
Matrix Metalloproteinases/ metabolism
Models, Animal
Myocardium/enzymology/ pathology
Reperfusion Injury/chemically induced/enzymology
Acute Disease
Catalysis/drug effects
Chronic Disease
Creatine Kinase/blood
Enzyme Inhibitors/pharmacology
Heart/ drug effects/physiopathology
Heart Failure/ chemically induced/physiopathology/prevention & control
L-Lactate Dehydrogenase/blood
Metalloporphyrins/ pharmacology
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
Antibiotics, Antineoplastic
Creatine Kinase/metabolism
Enzyme Activation/drug effects
Heart Failure/ chemically induced/pathology/physiopathology
Hemodynamics/drug effects
L-Lactate Dehydrogenase/metabolism
Poly(ADP-ribose) Polymerases/ genetics/ metabolism
Survival Analysis
Ventricular Function, Left/genetics
Benzamides/ pharmacology
Cells, Cultured
DNA Damage/drug effects
DNA Fragmentation/drug effects
Enzyme Activation/drug effects/physiology
Mitochondria/ drug effects
Nitrogen Oxides/ toxicity
Poly(ADP-ribose) Polymerases/ antagonists & inhibitors/metabolism
Protective Agents/ pharmacology
Thymus Gland/cytology/ drug effects
külföldön készült közlemény
Megjelenés:Medical Science Monitor. - 10 : 3 (2004), p. BR77-83. -
További szerzők:Bai Péter (1976-) (biokémikus) Bak István (1975-) (vegyész, analitikus, farmakológus) Pacher Pál Mabley, Jon G. Liaudet, Lucas Bakondi Edina (1975-) (biokémikus, vegyész) Gergely Pál (1947-) (biokémikus) Kollai, M. Szabó Csaba
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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