Sparing of mdx extraocular muscles from dystrophic pathology is not attributable to normalized concentration or distribution of neuronal nitric oxide synthase

Michelle Wehling, James T. Stull, Timothy J. McCabe, James G. Tidball

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Previous findings have led to speculations that decreased concentration of nNOS (neuronal nitric oxide synthase) may underlie some aspects of the pathophysiology of dystrophic muscle. We have tested whether the sparing of extraocular muscles (EOM) in muscular dystrophy is attributable to the presence of normal nNOS concentration and distribution in these muscles. Measurements of total nNOS concentration in control muscle showed that total nNOS comprises approximately 0.05% of total muscle protein, indicating a molar stoichiometry of approximately 60 and 20 to total dystrophin and syntrophin, respectively. Thus, most muscle nNOS is either not associated with the dystrophin complex, or binds to yet unidentified sites in the complex. nNOS concentration was at least two-fold greater in C57 EOM and tibialis anterior (TA) compared with mdx samples. No significant differences in nNOS concentration in EOM versus TA in either mdx or C57 mice were observed. nNOS was concentrated at the sarcolemma of all C57 samples, while mdx nNOS displayed a cytosolic distribution, except in fibers that reverted to express dystrophin. These data show that mdx EOM are spared by a mechanism other than normalized concentration and location of nNOS.

Original languageEnglish (US)
Pages (from-to)22-29
Number of pages8
JournalNeuromuscular Disorders
Volume8
Issue number1
DOIs
StatePublished - Feb 1998

Fingerprint

Oculomotor Muscles
Nitric Oxide Synthase Type I
Pathology
Dystrophin
Muscles
Sarcolemma
Muscle Proteins
Muscular Dystrophies

Keywords

  • Extraocular muscle
  • mdx mouse
  • Muscular dystrophy
  • Neuronal nitric oxide synthase
  • Skeletal muscle

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Neurology

Cite this

Sparing of mdx extraocular muscles from dystrophic pathology is not attributable to normalized concentration or distribution of neuronal nitric oxide synthase. / Wehling, Michelle; Stull, James T.; McCabe, Timothy J.; Tidball, James G.

In: Neuromuscular Disorders, Vol. 8, No. 1, 02.1998, p. 22-29.

Research output: Contribution to journalArticle

@article{55add4d5c6bd4b618461b248ee49a15f,
title = "Sparing of mdx extraocular muscles from dystrophic pathology is not attributable to normalized concentration or distribution of neuronal nitric oxide synthase",
abstract = "Previous findings have led to speculations that decreased concentration of nNOS (neuronal nitric oxide synthase) may underlie some aspects of the pathophysiology of dystrophic muscle. We have tested whether the sparing of extraocular muscles (EOM) in muscular dystrophy is attributable to the presence of normal nNOS concentration and distribution in these muscles. Measurements of total nNOS concentration in control muscle showed that total nNOS comprises approximately 0.05{\%} of total muscle protein, indicating a molar stoichiometry of approximately 60 and 20 to total dystrophin and syntrophin, respectively. Thus, most muscle nNOS is either not associated with the dystrophin complex, or binds to yet unidentified sites in the complex. nNOS concentration was at least two-fold greater in C57 EOM and tibialis anterior (TA) compared with mdx samples. No significant differences in nNOS concentration in EOM versus TA in either mdx or C57 mice were observed. nNOS was concentrated at the sarcolemma of all C57 samples, while mdx nNOS displayed a cytosolic distribution, except in fibers that reverted to express dystrophin. These data show that mdx EOM are spared by a mechanism other than normalized concentration and location of nNOS.",
keywords = "Extraocular muscle, mdx mouse, Muscular dystrophy, Neuronal nitric oxide synthase, Skeletal muscle",
author = "Michelle Wehling and Stull, {James T.} and McCabe, {Timothy J.} and Tidball, {James G.}",
year = "1998",
month = "2",
doi = "10.1016/S0960-8966(97)00136-3",
language = "English (US)",
volume = "8",
pages = "22--29",
journal = "Neuromuscular Disorders",
issn = "0960-8966",
publisher = "Elsevier Limited",
number = "1",

}

TY - JOUR

T1 - Sparing of mdx extraocular muscles from dystrophic pathology is not attributable to normalized concentration or distribution of neuronal nitric oxide synthase

AU - Wehling, Michelle

AU - Stull, James T.

AU - McCabe, Timothy J.

AU - Tidball, James G.

PY - 1998/2

Y1 - 1998/2

N2 - Previous findings have led to speculations that decreased concentration of nNOS (neuronal nitric oxide synthase) may underlie some aspects of the pathophysiology of dystrophic muscle. We have tested whether the sparing of extraocular muscles (EOM) in muscular dystrophy is attributable to the presence of normal nNOS concentration and distribution in these muscles. Measurements of total nNOS concentration in control muscle showed that total nNOS comprises approximately 0.05% of total muscle protein, indicating a molar stoichiometry of approximately 60 and 20 to total dystrophin and syntrophin, respectively. Thus, most muscle nNOS is either not associated with the dystrophin complex, or binds to yet unidentified sites in the complex. nNOS concentration was at least two-fold greater in C57 EOM and tibialis anterior (TA) compared with mdx samples. No significant differences in nNOS concentration in EOM versus TA in either mdx or C57 mice were observed. nNOS was concentrated at the sarcolemma of all C57 samples, while mdx nNOS displayed a cytosolic distribution, except in fibers that reverted to express dystrophin. These data show that mdx EOM are spared by a mechanism other than normalized concentration and location of nNOS.

AB - Previous findings have led to speculations that decreased concentration of nNOS (neuronal nitric oxide synthase) may underlie some aspects of the pathophysiology of dystrophic muscle. We have tested whether the sparing of extraocular muscles (EOM) in muscular dystrophy is attributable to the presence of normal nNOS concentration and distribution in these muscles. Measurements of total nNOS concentration in control muscle showed that total nNOS comprises approximately 0.05% of total muscle protein, indicating a molar stoichiometry of approximately 60 and 20 to total dystrophin and syntrophin, respectively. Thus, most muscle nNOS is either not associated with the dystrophin complex, or binds to yet unidentified sites in the complex. nNOS concentration was at least two-fold greater in C57 EOM and tibialis anterior (TA) compared with mdx samples. No significant differences in nNOS concentration in EOM versus TA in either mdx or C57 mice were observed. nNOS was concentrated at the sarcolemma of all C57 samples, while mdx nNOS displayed a cytosolic distribution, except in fibers that reverted to express dystrophin. These data show that mdx EOM are spared by a mechanism other than normalized concentration and location of nNOS.

KW - Extraocular muscle

KW - mdx mouse

KW - Muscular dystrophy

KW - Neuronal nitric oxide synthase

KW - Skeletal muscle

UR - http://www.scopus.com/inward/record.url?scp=0032005566&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032005566&partnerID=8YFLogxK

U2 - 10.1016/S0960-8966(97)00136-3

DO - 10.1016/S0960-8966(97)00136-3

M3 - Article

C2 - 9565987

AN - SCOPUS:0032005566

VL - 8

SP - 22

EP - 29

JO - Neuromuscular Disorders

JF - Neuromuscular Disorders

SN - 0960-8966

IS - 1

ER -