Open AccessNeuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy.
Author(s) -
Wen Jinn Chang,
Susan T. Iannaccone,
Kim S. Lau,
Bettie Sue Siler Masters,
Timothy J. McCabe,
Kirk McMillan,
Roanna C. Padre,
Melissa J. Spencer,
James G. Tidball,
James T. Stull
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.17.9142
Subject(s) - dystrophin , sarcolemma , muscular dystrophy , duchenne muscular dystrophy , itga7 , skeletal muscle , utrophin , nitric oxide synthase , chemistry , endocrinology , medicine , myocyte , biology , microbiology and biotechnology , nitric oxide
Neuronal nitric oxide synthase (nNOS) in fast-twitch skeletal muscle fibers is primarily particulate in contrast to its greater solubility in brain. Immunohistochemistry shows nNOS localized to the sarcolemma, with enrichment at force transmitting sites, the myotendinous junctions, and costameres. Because this distribution is similar to dystrophin, we determined if nNOS expression was affected by the loss of dystrophin. Significant nNOS immunoreactivity and enzyme activity was absent in skeletal muscle tissues from patients with Duchenne muscular dystrophy. Similarly, in dystrophin-deficient skeletal muscles from mdx mice both soluble and particulate nNOS was greatly reduced compared with C57 control mice. nNOS mRNA was also reduced in mdx muscle in contrast to mRNA levels for a dystrophin binding protein, alpha 1-syntrophin. nNOS levels increased dramatically from 2 to 52 weeks of age in C57 skeletal muscle, which may indicate a physiological role for NO in aging-related processes. Biochemical purification readily dissociates nNOS from the dystrophin-glycoprotein complex. Thus, nNOS is not an integral component of the dystrophin-glycoprotein complex and is not simply another dystrophin-associated protein since the expression of both nNOS mRNA and protein is affected by dystrophin expression.