TY - JOUR
T1 - Evidence for the production of peroxynitrite in inflammatory CNS demyelination
AU - Cross, Anne H.
AU - Manning, Pamela T.
AU - Stern, Michael K.
AU - Misko, Thomas P.
N1 - Funding Information:
The authors thank Richard M. Keeling and Manuel San for excellent technical assistance and Dr. John L. Trotter, Dr. Mark Currie, Dr. James A. Hewett, Dr. Michael K. Racke and Dr. Amy Lovett-Racke for helpful discussions. The Nikon photographic microscope used in these studies was a gift from the Multiple Sclerosis Foundation, Inc. Supported by grants from the National Multiple Sclerosis Society (RG-2621-A-3 to AHC) and Monsanto Co.
PY - 1997/12
Y1 - 1997/12
N2 - Peroxynitrite, which is generated by the reaction of nitric oxide (NO) with superoxide, is a strong oxidant that can damage subcellular organelles, membranes and enzymes through its actions on proteins, lipids, and DNA, including the nitration of tyrosine residues of proteins. Detection of nitrotyrosine (NT) serves as a biochemical marker of peroxynitrite-induced damage. In the present studies, NT was detected by immunohistochemistry in CNS tissues from mice with acute experimental autoimmune encephalomyelitis (EAE). NT immunoreactivity was displayed by many mononuclear inflammatory cells, including CD4+ cells. It was also observed in astrocytes near EAE lesions. Immunostaining for the inducible isoform of NO synthase (iNOS) was also observed, particularly during acute EAE. These data Strongly suggest that peroxynitrite formation is a major consequence of NO produced via iNOS, and implicate this powerful oxidant in the pathogenesis of EAE.
AB - Peroxynitrite, which is generated by the reaction of nitric oxide (NO) with superoxide, is a strong oxidant that can damage subcellular organelles, membranes and enzymes through its actions on proteins, lipids, and DNA, including the nitration of tyrosine residues of proteins. Detection of nitrotyrosine (NT) serves as a biochemical marker of peroxynitrite-induced damage. In the present studies, NT was detected by immunohistochemistry in CNS tissues from mice with acute experimental autoimmune encephalomyelitis (EAE). NT immunoreactivity was displayed by many mononuclear inflammatory cells, including CD4+ cells. It was also observed in astrocytes near EAE lesions. Immunostaining for the inducible isoform of NO synthase (iNOS) was also observed, particularly during acute EAE. These data Strongly suggest that peroxynitrite formation is a major consequence of NO produced via iNOS, and implicate this powerful oxidant in the pathogenesis of EAE.
KW - Demyelination
KW - Experimental autoimmune (allergic) encephalomyelitis
KW - Nitric Oxide
KW - Peroxynitrite anion
UR - http://www.scopus.com/inward/record.url?scp=0031457801&partnerID=8YFLogxK
U2 - 10.1016/S0165-5728(97)00145-8
DO - 10.1016/S0165-5728(97)00145-8
M3 - Article
C2 - 9413267
AN - SCOPUS:0031457801
SN - 0165-5728
VL - 80
SP - 121
EP - 130
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -