NITRIC-OXIDE-SYNTHASE-I (NOS-I) IS DEFICIENT IN THE SARCOLEMMA OF STRIATED-MUSCLE FIBERS IN PATIENTS WITH DUCHENNE MUSCULAR-DYSTROPHY, SUGGESTING AN ASSOCIATION WITH DYSTROPHIN

Previously, we have demonstrated the expression of the brain-type nitr ic oxide synthase (NOS-I) in the sarcolemmal region of somatic and vis ceral striated muscle fibers in a variety of mammalian species through the use of enzyme histochemical and immunochemical techniques. Here w e report that NOS-I protein and its NADPH diaphorase (NADPHd) activity are co-localized in the sarcolemma of human skeletal muscles. NOS-I i mmunolabeling and NADPHd activity showed no significant variation betw een type I and II fibers. In muscle biopsy specimens from patients wit h Duchenne muscular dystrophy (DMD), both NOS-I protein and activity w ere absent or markedly reduced. We, therefore, propose that NOS-I is c omplexed with dystrophin and/or dystrophin-associated proteins, adding a novel member to the sarcolemmal dystrophin-glycoprotein complex (DG C). The nature of the NOS-I-DGC link, and its role in skeletal muscle physiology and pathophysiology remain to be elucidated.