Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy.

• DOI: 10.1073/pnas.93.17.9142
• Publication Date: 2002-07-26T14:34:16Z
• Authors: W J Chang; S T Iannaccone; K S Lau; B S Masters; T J McCabe; K McMillan; R C Padre; M J Spencer; J G Tidball; J T Stull
• Keywords: Neurons; 0303 health sciences; Calcium-Binding Proteins; Cell Membrane; Membrane Proteins; Muscle Proteins; Immunohistochemistry; Muscular Dystrophies; Dystrophin; Mice; 03 medical and health sciences; Intercellular Junctions; Mice, Inbred mdx; Animals; Humans; RNA, Messenger; Nitric Oxide Synthase; Muscle, Skeletal; Glycoproteins

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.