NEURONAL NITRIC-OXIDE SYNTHASE AND DYSTROPHIN-DEFICIENT MUSCULAR-DYSTROPHY

Neuronal nitric oxide synthase (nNOS) in fast-twitch skeletal muscle f ibers is primarily particulate in contrast to its greater solubility i n brain, Immunohistochemistry shows nNOS localized to the sarcolemma, with enrichment at force transmitting sites, the myotendinous junction s, and costameres, Because this distribution is similar to dystrophin, we determined if nNOS expression was affected by the loss of dystroph in, Significant nNOS immunoreactivity and enzyme activity was absent i n skeletal muscle tissues from patients with Duchenne muscular dystrop hy, Similarly, in dystrophin-deficient skeletal muscles from mdr mice both soluble and particulate nNOS was greatly reduced compared with C5 7 central mice, nNOS mRNA was also reduced in mdr muscle in contrast t o mRNA levels for a dystrophin binding protein, alpha 1-syntrophin, nN OS levels increased dramatically from 2 to 52 weeks of age in C57 skel etal muscle, which mag indicate a physiological role for NO in aging-r elated processes, Biochemical purification readily dissociates nNOS fr om the dystrophin-glycoprotein complex. Thus, nNOS is not an integral comp one nt of the dystrophin-glycoprotein complex and is not simply a nother dystrophin-associated protein since the expression of both nNOS mRNA and protein is affected by dystrophin expression.