Role of poly(ADP-ribose) synthetase activation in the development of experimental allergic encephalomyelitis.
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.
Scott
G S
GS
Department of Microbiology and Immunology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA. gwen.scott@mail.tju.edu
Hake
P
P
Kean
R B
RB
Virág
L
L
Szabó
C
C
Hooper
D C
DC
D000818:Animals; D003374:Coumarins / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology / Q000209:etiology* / Q000517:prevention & control; D004789:Enzyme Activation; D007150:Immunohistochemistry; D008297:Male; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000737:chemistry; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
D003374:Coumarins; C071383:5-iodo-6-amino-1,2-benzopyrone; C002744:3-nitrotyrosine; D014443:Tyrosine; D011065:Poly(ADP-ribose) Polymerases