Evidence for the production of peroxynitrite in inflammatory CNS demyelination.
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.
Cross
A H
AH
Department of Neurology and Neurosurgery, Washington University School of Medicine, St. Louis, MO 63110, USA. crossa@neuro.wustl.edu
Manning
P T
PT
Stern
M K
MK
Misko
T P
TP
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000032:analysis; D012008:Recurrence; D012074:Remission Induction; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D009566:Nitrates; C039642:peroxynitric acid; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase