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001-es BibID:	BIBFORM028393
Első szerző:	Scott, Gwen S.
Cím:	Role of poly(ADP-ribose) synthetase activation in the development of experimental allergic encephalomyelitis / G. S. Scott, P. Hake, R. B. Kean, L. Virág, Cs. Szabó, D. C. Hooper
Dátum:	2001
ISSN:	0165-5728
Megjegyzések:	Peroxynitrite formation has been demonstrated during experimental allergic encephalomyelitis (EAE). Furthermore, peroxynitrite has been identified as an activator of poly(ADP-ribose) synthetase (PARS), an enzyme implicated in neurotoxicity. In the current study, we examined the role of PARS activation in the development of EAE. Administration of the PARS inhibitor 5-iodo-6-amino-1,2-benzopyrone (INH2BP) delayed the onset of EAE and reduced the incidence and severity of disease signs. Moreover, drug treatment lowered iNOS activity and decreased cell infiltration in cervical spinal tissues from EAE-sensitized animals. To conclude, the results of the present investigation suggest that PARS activity may contribute to the pathogenesis of EAE.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban experimental allergic encephalomyelitis poly(ADP-ribose) synthase peroxynitrite inflammation blood-brain barrier külföldön készült közlemény
Megjelenés:	Journal of Neuroimmunology 117 : 1-2 (2001), p. 78-86. -
További szerzők:	Hake, Paul Kean, R. B. Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Szabó Csaba (1967-) (orvos) Hooper, D. Craig
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat DOI
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001-es BibID:	BIBFORM028456
Első szerző:	Szabó Csaba (orvos)
Cím:	Protection against peroxynitrite-induced fibroblast injury and arthritis development by inhibition of poly(ADP-ribose) synthase / Csaba Szabó, László Virág, Salvatore Cuzzocrea, Gwen S. Scott, Paul Hake, Michael P. O'Connor, Basilia Zingarelli, Andrew Salzman, Ernest Kun
Dátum:	1998
ISSN:	0027-8424
Megjegyzések:	Peroxynitrite, a cytotoxic oxidant formed from nitric oxide (NO) and superoxide, induces DNA strand breakage, which activates the nuclear enzyme poly(ADP-ribose) synthase (PARS; EC 2.4.2.30). The cellular function of PARS was determined in fibroblast lines from PARS knockout animals (PARS-/-) and corresponding wild-type animals (PARS+/+), with the aid of the lipophilic PARS inhibitor 5-iodo-6-amino-1,2-benzopyrone (INH2BP). We investigated the role of PARS in peroxynitrite-induced fibroblast injury in vitro and also in the development of arthritis in vivo. Exposure of embryonic fibroblasts from the PARS+/+ animals to peroxynitrite caused DNA single-stand breakage and PARS activation and caused an acute suppression of mitochondrial respiration. INH2BP protected the PARS+/+ cells against the suppression of mitochondrial respiration in response to peroxynitrite (50-100 microM). Similarly to PARS inhibition with INH2BP, the PARS-/- cells were protected against peroxynitrite-induced injury. The protection against cellular injury by PARS-/- phenotype or INH2BP waned when cells were challenged with higher concentrations of the oxidant. Inhibition of PARS by INH2BP or by PARS-/- phenotype reduced inducible nitric-oxide synthase (iNOS; EC 1.14.13.39) mRNA levels and inhibited production of NO in immunostimulated cells. INH2BP had no peroxynitrite scavenging or hydroxyl radical scavenging effects, and it exerted no additional (nonspecific) effects in the PARS-/- cells. In collagen-induced arthritis, significant staining for nitrotyrosine, a marker of peroxynitrite formation, was found in the inflamed joints. Oral treatment with INH2BP (0.5 g/kg, daily), starting at the onset of arthritis (day 25), delayed the development of the clinical signs at days 26-35 and improved histological status in the knee and paw. Our data demonstrate that deletion of PARS by genetic manipulation or pharmacological inhibition of PARS protects against oxidant-induced cellular injury in vitro and exhibits anti-inflammatory effects in vivo.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban nitric oxide superoxide inflammation DNA single-strand break inducible nitric-oxide synthase külföldön készült közlemény
Megjelenés:	Proceedings of The National Academy Of Sciences of The United States Of America 95 : 7 (1998), p. 3867-3872. -
További szerzők:	Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Cuzzocrea, Salvatore Scott, Gwen S. Hake, Paul O'Connor, Michael Zingarelli, Basilia Salzman, Andrew L. Kun, Ernest
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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