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Nitric oxide-induced oxidative stress in autosomal recessive and dominant inclusion-body myopathies.

Authors
  • Yang, C C
  • Alvarez, R B
  • Engel, W K
  • Heller, S L
  • Askanas, V
Type
Published Article
Journal
Brain : a journal of neurology
Publication Date
Jun 01, 1998
Volume
121 ( Pt 6)
Pages
1089–1097
Identifiers
PMID: 9648544
Source
Medline
License
Unknown

Abstract

Autosomal-recessive and autosomal-dominant hereditary inclusion-body myopathies are severe, progressive muscle diseases, characterized pathologically by vacuolated muscle fibres containing paired helical filaments. We immunostained muscle biopsy specimens from quadriceps-sparing autosomal-recessive and autosomal-dominant inclusion-body myopathy subjects, disease-control subjects and normal patients, utilizing isoform-specific antibodies against the neuronal and inducible forms of nitric oxide synthase, and antibodies against nitrotyrosine. Approximately 75% of the vacuolated muscle fibres in all recessive and dominant inclusion-body myopathy patients contained inclusions strongly immunoreactive with antibodies against neuronal and inducible nitric oxide synthase which, by immunoelectron microscopy, were colocalized to clusters of tubulofilaments (previously shown, by us, to be paired helical filaments). Strong nitrotyrosine immunoreactivity was in the form of multiple dots and large granular patches, which ultrastructurally did not immunolocalize to tubulofilaments. Excess intracellular nitric oxide can combine with superoxide to produce highly toxic peroxynitrite, which can nitrate tyrosines of proteins. The presence of nitrotyrosine is indicative of nitric oxide-induced oxidative stress. Our data suggest that oxidative stress plays a role in the pathogenic cascade of hereditary inclusion-body myopathies.

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