INCREASE OF NITRIC-OXIDE SYNTHASES AND NITROTYROSINE IN INCLUSION-BODY MYOSITIS

To investigate the possible role of nitric oxide (NO)induced 'oxidativ e stress' in the pathogenesis of inclusion-body myositis (IBM), we imm unostained muscle biopsies of 12 patients with IBM with isoform-specif ic 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 immuno reactive 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 peroxynitrit e, which can nitrate tyrosines of proteins. The presence of nitrotyros ine is indicative of NO-induced 'oxidative stress'. Our data suggest t hat this mechanism may play a pathogenic role in IBM.