Role of poly(ADP-ribose) synthetase activation in the development of experimental allergic encephalomyelitis

G. S. Scott; P. Hake; R. B. Kean; L. Virág; C. Szabó; D. C. Hooper

doi:10.1016/S0165-5728(01)00329-0

Role of poly(ADP-ribose) synthetase activation in the development of experimental allergic encephalomyelitis

G. S. Scott, P. Hake, R. B. Kean, L. Virág, C. Szabó, D. C. Hooper

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	78-86
Number of pages	9
Journal	Journal of Neuroimmunology
Volume	117
Issue number	1-2
DOIs	https://doi.org/10.1016/S0165-5728(01)00329-0
State	Published - Jul 2 2001

Keywords

Blood-brain barrier
Experimental allergic encephalomyelitis
Inflammation
Peroxynitrite
Poly(ADP-ribose) synthetase

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Neurology
Clinical Neurology

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10.1016/S0165-5728(01)00329-0

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title = "Role of poly(ADP-ribose) synthetase activation in the development of experimental allergic encephalomyelitis",

abstract = "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.",

keywords = "Blood-brain barrier, Experimental allergic encephalomyelitis, Inflammation, Peroxynitrite, Poly(ADP-ribose) synthetase",

author = "Scott, {G. S.} and P. Hake and Kean, {R. B.} and L. Vir{\'a}g and C. Szab{\'o} and Hooper, {D. C.}",

note = "Funding Information: The assistance of Mr. Michael O'Conor with the iNOS activity measurements is greatly appreciated. This work was supported, in part, by a grant from Octamer (Mill Valley, CA) (to C.S. and G.S.S.) and by National Multiple Sclerosis Society grant RG2896A8/5 (to D.C.H.). G.S.S. was supported by a grant from the Paralyzed Veterans of America Spinal Cord Research Foundation.",

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doi = "10.1016/S0165-5728(01)00329-0",

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AU - Scott, G. S.

AU - Hake, P.

AU - Kean, R. B.

AU - Virág, L.

AU - Szabó, C.

AU - Hooper, D. C.

N1 - Funding Information: The assistance of Mr. Michael O'Conor with the iNOS activity measurements is greatly appreciated. This work was supported, in part, by a grant from Octamer (Mill Valley, CA) (to C.S. and G.S.S.) and by National Multiple Sclerosis Society grant RG2896A8/5 (to D.C.H.). G.S.S. was supported by a grant from the Paralyzed Veterans of America Spinal Cord Research Foundation.

PY - 2001/7/2

Y1 - 2001/7/2

N2 - 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.

AB - 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.

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Role of poly(ADP-ribose) synthetase activation in the development of experimental allergic encephalomyelitis

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