title: Increase of nitric oxide synthases and nitrotyrosine in inclusion-body myositis.
abstract: To investigate the possible role of nitric oxide (NO)-induced 'oxidative stress' in the pathogenesis of inclusion-body myositis (IBM), we immunostained muscle biopsies of 12 patients with IBM with isoform-specific antibodies against the neuronal and inducible forms of nitric oxide synthase and with antibodies against nitrotyrosine. Between 70 and 80% of IBM vacuolated muscle fibers contained inclusions strongly immunoreactive with all three antibodies, which by immuno-electronmicroscopy co-localized mainly to cytoplasmic paired-helical filaments, and also to amorphous structures and floccular material. Excess intracellular NO can combine with superoxide to produce highly reactive peroxynitrite which can nitrate tyrosines of proteins. The presence of nitrotyrosine is indicative of NO-induced "oxidative stress'. Our data suggest that this mechanism may play a pathogenic role in IBM.
authors.affiliation: Department of Neurology, University of Southern California School of Medicine, Good Samaritan Hospital, Los Angeles 90017-1912, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Yang
authors.forename: R B
authors.initials: RB
authors.lastname: Alvarez
authors.forename: W K
authors.initials: WK
authors.lastname: Engel
authors.forename: V
authors.initials: V
authors.lastname: Askanas
mesh_terms: D004790:Enzyme Induction / Q000502:physiology; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007150:Immunohistochemistry; D016253:Microscopy, Immunoelectron; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000378:metabolism; D009135:Muscular Diseases / Q000201:enzymology / Q000378:metabolism; D018979:Myositis, Inclusion Body / Q000201:enzymology / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase