Summary
Recently, it has been shown that in human striated muscle the signalling enzyme, brain-type nitric oxide synthase I (NOS I), is associated with the sarcolemma and complexes with dystrophin and/or members of the dystrophin complex. In order to find out whether there exists a regular association between NOS I and the complex, muscle biopsies from patients with various muscle disorders were analysed by enzyme histochemistry and immunohistochemistry. In patients suffering from Duchenne muscular dystrophy, and to a lesser extent in those with Becker-type dystrophy, NOS I and dystrophin complex components were absent or drastically reduced in the sarcolemma region. In other dystrophies, as well as in metabolic and inflammatory myopathies, NOS I and dystrophin complex constituents were expressed normally, while in the case of neurogenic diseases leading to denervation atrophy and especially congenital idiopathic clubfoot, the immunohistochemical patterns of the distribution of the dystrophin complex constituents were normal, but NOS I activity and protein were deficient or dramatically diminished. The results can be interpreted as indicating that, in general, NOS I targeting to the sarcolemma is dependent on particular members of the dystrophin complex, such as ·-1 syntrophin, yet the expression and/or positioning of NOS I may be under the control of further factors, probably of neurogenic origin. NOS I-associated diaphorase may thus be a useful complementary tool in the diagnosis of muscle disorders.
Similar content being viewed by others
References
Brenman, J.E., Chao, D.S., Xia, H., Aldape, K. & Bredt, D.S. (1995) Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy. Cell 82, 743-52.
Brenman, J.E., Chao, D.S., Gee, S.H., Mcgee, A.W., Craven, S.E., Santillano, D.R., Wu, Z., Huang, F., Xia, H., Peters, M.F., Froehner, S.C. & Bredt, D.S. (1996) Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and · 1-syntrophin mediated by PDZ domains. Cell 84, 757-67.
Cullen, M.J. & Mastaglia, F.L. (1982) Pathological reactions of skeletal muscle. In Skeletal Muscle Pathology (edited by Mastaglia, F.L. & Walton, J.), pp. 88-139. Edinburgh: Churchill Livingstone.
Dahrmann, G. & Gossrau, R. (1996) Nitric oxide synthase (NOS) I immunoreactivity and NOS-associated-NADPH diaphorase (NOSaNADPHd) histochemistry in mouse skeletal muscle during post-natal development. Ann. Anat. (Suppl.) 178, 229-30.
Gossrau, R., Christova, T., Grozdanovic, Z. & Blottner, D. (1996) Adhalin (·-sarcoglycan) is not required for anchoring of nitric oxide synthase I (NOS I) to the sarcolemma in non-mammalian skeletal (striated) muscle fibers. Acta Histochem. 98, 345-55.
Grozdanovic, Z., Nakos, G., Mayer, B. & Gossrau, R. (1995a) A modified method allows for correlation between NADPH-diaphorase histochemistry and immunohistochemistry for the demonstration of neuronal nitric oxide synthase (nNOS). Folia Histochem. Cytobiol. 33, 11-18.
Grozdanovic, Z., Nakos, G., Dahrmann, G., Mayer, B. & Gossrau, R. (1995b) Species-independent expression of nitric oxide synthase in the sarcolemma region of visceral and somatic striated muscle fibers. Cell Tissue Res. 281, 493-99.
Grozdanovic, Z., Nakos, G., Christova, T., Nikolova, Z., Mayer, B. & Gossrau, R. (1995c) Demonstration of nitric oxide synthase (NOS) in marmosets by NADPH diaphorase (NADPH-d) histochemistry and NOS immunoreactivity. Acta Histochem. 97, 321-32.
Grozdanovic, Z., Gosztonyi, G. & Gossrau, R. (1996) 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. Acta Histochem. 98, 61-69.
Kobzik, L., Reid, M.B., Bredt, D.S. & Stamler, J.S. (1994) Nitric oxide in skeletal muscle. Nature 372, 546-48.
Nakos, G. & Gossrau, R. (1994) When NADPH diaphorase (NADPHd) works in the presence of formaldehyde, the enzyme appears to visualize selectively cells with constitutive nitric oxide synthase (NOS). Acta Histochem. 96, 335-43.
Scherer-Singler, U., Vincent, S.R., Kimura, H. & Mcgeer, E.G. (1983) Demonstration of a unique population of neurons with NADPH-diaphorase histochemistry. J. Neurosci. Meth. 9, 229-34.
Thomas, E. & Pearse, A.G.E. (1961) The fine localization of dehydrogenases in the nervous system. Histochemie 2, 266-82.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Grozdanovic, Z., Christova, T., Gosztonyi, G. et al. Absence of nitric oxide synthase I despite the presence of the dystrophin complex in human striated muscle. J Mol Hist 29, 97–104 (1997). https://doi.org/10.1023/A:1026425120156
Issue Date:
DOI: https://doi.org/10.1023/A:1026425120156