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

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.

[1]  Y. Agid,et al.  Nitric oxide synthase and neuronal vulnerability in parkinson's disease , 1996, Neuroscience.

[2]  W. Engel,et al.  Sporadic inclusion-body myositis and hereditary inclusion-body myopathies: diseases of oxidative stress and aging? , 1998, Archives of neurology.

[3]  W. Engel,et al.  βAPP gene transfer into cultured human muscle induces inclusion‐body myositis aspects , 1997 .

[4]  K. Weisgraber,et al.  Apolipoprotein E and apolipoprotein E messenger RNA in muscle of inclusion body myositis and myopathies , 1996, Annals of neurology.

[5]  T. Dawson,et al.  Gases as biological messengers: nitric oxide and carbon monoxide in the brain , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  D. Perl,et al.  Evidence of neuronal oxidative damage in Alzheimer's disease. , 1996, The American journal of pathology.

[7]  W. Engel,et al.  Prion protein is abnormally accumulated in inclusion‐body myositis , 1993, Neuroreport.

[8]  E. El-Fakahany,et al.  beta-Amyloid 25-35 activates nitric oxide synthase in a neuronal clone. , 1993, Neuroreport.

[9]  J. Beckman,et al.  The role of peroxynitrite in nitric oxide-mediated toxicity. , 1995, Current topics in microbiology and immunology.

[10]  Y. Itoyama,et al.  Induction of nitrotyrosine-like immunoreactivity in the lower motor neuron of amyotrophic lateral sclerosis , 1995, Neuroscience Letters.

[11]  W. Engel,et al.  Abnormal accumulation of prion protein mRNA in muscle fibers of patients with sporadic inclusion-body myositis and hereditary inclusion-body myopathy. , 1994, The American journal of pathology.

[12]  W. Engel,et al.  β‐Amyloid precursor epitopes in muscle fibers of inclusion body myositis , 1993 .

[13]  J S Beckman,et al.  Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. , 1996, The American journal of physiology.

[14]  J Miller,et al.  Inclusion body myositis in HIV-1 and HTLV-1 infected patients. , 1996, Brain : a journal of neurology.

[15]  A. Taniguchi,et al.  Role of SOD-1 and nitric oxide/cyclic GMP cascade on neurofilament aggregation in ALS/MND , 1996, Journal of the Neurological Sciences.

[16]  W. Engel,et al.  New advances in the understanding of sporadic inclusion‐body myositis and hereditary inclusion‐body myopathies , 1995, Current opinion in rheumatology.

[17]  M. Dalakas,et al.  The spectrum of familial inclusion body myopathies in 13 families and a description of a quadriceps-sparing phenotype in non-Iranian Jews , 1996, Neurology.

[18]  W. Engel,et al.  Use of anti‐neurofilament antibody to identify paired‐helical filaments in inclusion‐body myositis , 1996, Annals of neurology.

[19]  W. Engel,et al.  Light and electron microscopic localization of beta-amyloid protein in muscle biopsies of patients with inclusion-body myositis. , 1992, The American journal of pathology.

[20]  W. Engel,et al.  Transfer of beta-amyloid precursor protein gene using adenovirus vector causes mitochondrial abnormalities in cultured normal human muscle. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[21]  E. Mandelkow,et al.  Oxidation of cysteine-322 in the repeat domain of microtubule-associated protein tau controls the in vitro assembly of paired helical filaments. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[22]  D. Selkoe,et al.  Recognition of Alzheimer paired helical filaments by monoclonal neurofilament antibodies is due to crossreaction with tau protein. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[23]  C. Behl,et al.  Hydrogen peroxide mediates amyloid β protein toxicity , 1994, Cell.

[24]  池内 健,et al.  Gene locus for autosomal recessive distal myopathy with rimmedvacuoles maps to chromosome 9 , 1996 .

[25]  H. Mizusawa,et al.  Histological determination of nitric oxide synthase (NOS) and NADPH-diaphorase in ragged-red fibers from patients with mitochondrial encephalomyopathies , 1997, Journal of the Neurological Sciences.

[26]  W. Engel,et al.  Difference in Expression of Phosphorylated Tau Epitopes between Sporadic Inclusion‐body Myositis and Hereditary Inclusion‐body Myopathies , 1996, Journal of neuropathology and experimental neurology.

[27]  W. Engel,et al.  Sporadic inclusion-body myositis and hereditary inclusion-body myopathies: current concepts of diagnosis and pathogenesis. , 1998, Current opinion in rheumatology.

[28]  M. N. Wallace,et al.  Nitric oxide synthase in reactive astrocytes adjacent to beta-amyloid plaques. , 1997, Experimental neurology.

[29]  W. Engel,et al.  Immunolocalization of ubiquitin in muscle biopsies of patients with inclusion body myositis and oculopharyngeal muscular dystrophy , 1991, Neuroscience Letters.

[30]  S. Tsuji,et al.  Gene locus for autosomal recessive distal myopathy with rimmed vacuoles maps to chromosome 9 , 1997, Annals of neurology.

[31]  L. Sternberger,et al.  Aberrant neurofilament phosphorylation in Alzheimer disease , 1987 .

[32]  L. Sternberger,et al.  Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neurofilaments in situ. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[33]  D. Selkoe,et al.  Twisted tubulofilaments of inclusion body myositis muscle resemble paired helical filaments of Alzheimer brain and contain hyperphosphorylated tau. , 1994, The American journal of pathology.

[34]  S. Dimauro,et al.  Multiple mitochondrial DNA deletions in sporadic inclusion body myositis: A study of 56 patients , 1996, Annals of neurology.

[35]  J. Wood,et al.  Abnormal phosphorylation of tau proteins associated with bovine brain microtubules: Activation by excess ATP and tyrosine dephosphorylation , 1994, Journal of neuroscience research.

[36]  D. Dickson,et al.  Recognition of tau epitopes by anti-neurofilament antibodies that bind to Alzheimer neurofibrillary tangles. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[37]  E. Holme,et al.  Mitochondrial DNA Deletions in Muscle Fibers in Inclusion Body Myositis , 1995, Journal of neuropathology and experimental neurology.

[38]  W. Engel,et al.  Immunolocalization of Nitric Oxide Synthases at the Postsynaptic Domain of Human and Rat Neuromuscular Junctions—Light and Electron Microscopic Studies , 1997, Experimental Neurology.

[39]  M. Nakane,et al.  Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions. , 1994, Hypertension.

[40]  W. Engel.  Muscle biopsies in neuromuscular diseases. , 1967, Pediatric clinics of North America.

[41]  W. Engel,et al.  Increase of nitric oxide synthases and nitrotyrosine in inclusion‐body myositis , 1996, Neuroreport.

[42]  C. Nathan,et al.  Regulation of biosynthesis of nitric oxide. , 1994, The Journal of biological chemistry.

[43]  G. Burnstock,et al.  Mitochondrial nitric oxide synthase: a ubiquitous regulator of oxidative phosphorylation? , 1996, Biochemical and biophysical research communications.

[44]  W. Engel,et al.  beta-Amyloid precursor protein mRNA is increased in inclusion-body myositis muscle. , 1993, Neuroreport.

[45]  A. Gow,et al.  Effects of peroxynitrite‐induced protein modifications on tyrosine phosphorylation and degradation , 1996, FEBS letters.

[46]  W. Engel,et al.  New advances in inclusion-body myositis. , 1993, Current opinion in rheumatology.

[47]  V. Askanas,et al.  New developments in hereditary inclusion body myopathies , 1997, Annals of neurology.

[48]  S. Mitrani‐Rosenbaum,et al.  Various types of herediary inclusion body myopathies map to chromosome 9p1‐q1 , 1997, Annals of neurology.

[49]  Joseph S. Beckman,et al.  Widespread Peroxynitrite-Mediated Damage in Alzheimer’s Disease , 1997, The Journal of Neuroscience.