Loss of sarcolemmal nNOS is common in acquired and inherited neuromuscular disorders

E. L. Finanger Hedderick, J. L. Simmers, A. Soleimani, E. Andres-Mateos, Ruth Marx-Rattner, D. C. Files, Landon Stuart King, Thomas Owen Crawford, Andrea Markl Corse, R. D. Cohn

Research output: Contribution to journalArticle

Abstract

Objective: Neuronal nitric oxide synthase (nNOS), normally expressed at the sarcolemmal membrane, is known to be mislocalized to the sarcoplasm in several forms of muscular dystrophy. Our objectives were to characterize further the range of patients manifesting aberrant nNOS sarcolemmal immunolocalization and to study nNOS localization in animal models of nondystrophic myopathy. Methods: We carried out a retrospective cross-sectional study. We performed immunofluorescent staining for nNOS on biopsy specimens from 161 patients with acquired and nondystrophin inherited neuromuscular conditions. The localization of sarcolemmal nNOS correlated with mobility and functional status. Muscle specimens from mouse models of steroid-induced and starvation-related atrophy were studied for qualitative and quantitative nNOS expression. Results: Sarcolemmal nNOS staining was abnormal in 42% of patients with inherited myopathic conditions, 25% with acquired myopathic conditions, 57% with neurogenic conditions, and 93% with hypotonia. Interestingly, we found significant associations between mobility status or muscle function and sarcolemmal nNOS expression. Furthermore, mouse models of catabolic stress also demonstrated mislocalization of sarcolemmal nNOS. Conclusion: Our analyses indicate that nNOS mislocalization is observed in a broad range of nondystrophic neuromuscular conditions associated with impaired mobility status and catabolic stress. Our findings suggest that the assessment of sarcolemmal localization of nNOS represents an important tool for the evaluation of muscle biopsies of patients with a variety of inherited and acquired forms of neuromuscular disorders.

Original languageEnglish (US)
Pages (from-to)960-967
Number of pages8
JournalNeurology
Volume76
Issue number11
DOIs
StatePublished - Mar 15 2011

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Nitric Oxide Synthase Type I
Muscular Diseases
Muscles
Staining and Labeling
Biopsy
Muscle Hypotonia
Muscular Dystrophies
Starvation
Atrophy
Animal Models
Cross-Sectional Studies
Steroids

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Finanger Hedderick, E. L., Simmers, J. L., Soleimani, A., Andres-Mateos, E., Marx-Rattner, R., Files, D. C., ... Cohn, R. D. (2011). Loss of sarcolemmal nNOS is common in acquired and inherited neuromuscular disorders. Neurology, 76(11), 960-967. https://doi.org/10.1212/WNL.0b013e31821043c8

Loss of sarcolemmal nNOS is common in acquired and inherited neuromuscular disorders. / Finanger Hedderick, E. L.; Simmers, J. L.; Soleimani, A.; Andres-Mateos, E.; Marx-Rattner, Ruth; Files, D. C.; King, Landon Stuart; Crawford, Thomas Owen; Corse, Andrea Markl; Cohn, R. D.

In: Neurology, Vol. 76, No. 11, 15.03.2011, p. 960-967.

Research output: Contribution to journalArticle

Finanger Hedderick, EL, Simmers, JL, Soleimani, A, Andres-Mateos, E, Marx-Rattner, R, Files, DC, King, LS, Crawford, TO, Corse, AM & Cohn, RD 2011, 'Loss of sarcolemmal nNOS is common in acquired and inherited neuromuscular disorders', Neurology, vol. 76, no. 11, pp. 960-967. https://doi.org/10.1212/WNL.0b013e31821043c8
Finanger Hedderick EL, Simmers JL, Soleimani A, Andres-Mateos E, Marx-Rattner R, Files DC et al. Loss of sarcolemmal nNOS is common in acquired and inherited neuromuscular disorders. Neurology. 2011 Mar 15;76(11):960-967. https://doi.org/10.1212/WNL.0b013e31821043c8
Finanger Hedderick, E. L. ; Simmers, J. L. ; Soleimani, A. ; Andres-Mateos, E. ; Marx-Rattner, Ruth ; Files, D. C. ; King, Landon Stuart ; Crawford, Thomas Owen ; Corse, Andrea Markl ; Cohn, R. D. / Loss of sarcolemmal nNOS is common in acquired and inherited neuromuscular disorders. In: Neurology. 2011 ; Vol. 76, No. 11. pp. 960-967.
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AU - Soleimani, A.

AU - Andres-Mateos, E.

AU - Marx-Rattner, Ruth

AU - Files, D. C.

AU - King, Landon Stuart

AU - Crawford, Thomas Owen

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AU - Cohn, R. D.

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