Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy

Wen Jinn Chang, Susan T. Iannaccone, Kim S. Lau, Bettie Sue S Masters, Timothy J. Mccabe, Kirk Mcmillan, Roanna C. Padre, Melissa J. Spencer, James G. Tidball, James T. Stull

Research output: Contribution to journalArticle

287 Citations (Scopus)

Abstract

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, α1-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.

Original languageEnglish (US)
Pages (from-to)9142-9147
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number17
DOIs
StatePublished - Aug 20 1996

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Nitric Oxide Synthase Type I
Dystrophin
Muscular Dystrophies
Skeletal Muscle
Messenger RNA
Costameres
Dystrophin-Associated Proteins
Glycoproteins
Fast-Twitch Muscle Fibers
Inbred mdx Mouse
Muscles
Sarcolemma
Duchenne Muscular Dystrophy
Skeletal Muscle Fibers
Solubility
Carrier Proteins
Immunohistochemistry

Keywords

  • Duchenne muscular dystrophy
  • mdx mice
  • myotendinous junctions
  • skeletal muscle
  • syntrophin

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Chang, W. J., Iannaccone, S. T., Lau, K. S., Masters, B. S. S., Mccabe, T. J., Mcmillan, K., ... Stull, J. T. (1996). Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy. Proceedings of the National Academy of Sciences of the United States of America, 93(17), 9142-9147. https://doi.org/10.1073/pnas.93.17.9142

Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy. / Chang, Wen Jinn; Iannaccone, Susan T.; Lau, Kim S.; Masters, Bettie Sue S; Mccabe, Timothy J.; Mcmillan, Kirk; Padre, Roanna C.; Spencer, Melissa J.; Tidball, James G.; Stull, James T.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 17, 20.08.1996, p. 9142-9147.

Research output: Contribution to journalArticle

Chang, WJ, Iannaccone, ST, Lau, KS, Masters, BSS, Mccabe, TJ, Mcmillan, K, Padre, RC, Spencer, MJ, Tidball, JG & Stull, JT 1996, 'Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy', Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 17, pp. 9142-9147. https://doi.org/10.1073/pnas.93.17.9142
Chang, Wen Jinn ; Iannaccone, Susan T. ; Lau, Kim S. ; Masters, Bettie Sue S ; Mccabe, Timothy J. ; Mcmillan, Kirk ; Padre, Roanna C. ; Spencer, Melissa J. ; Tidball, James G. ; Stull, James T. / Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy. In: Proceedings of the National Academy of Sciences of the United States of America. 1996 ; Vol. 93, No. 17. pp. 9142-9147.
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