Loss of sarcolemma nNOS in sarcoglycan-deficient muscle

Rachelle H Crosbie; Rita Barresi; Kevin P Campbell

doi:10.1096/fj.02-0519com

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Loss of sarcolemma nNOS in sarcoglycan-deficient muscle

Journal article

Peer reviewed

Loss of sarcolemma nNOS in sarcoglycan-deficient muscle

Rachelle H Crosbie, Rita Barresi and Kevin P Campbell

The FASEB journal, Vol.16(13), pp.1786-1791

11/2002

DOI: 10.1096/fj.02-0519com

PMID: 12409321

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Abstract

nNOS, anchored to the sarcolemma through its interactions with the dystrophin-glycoprotein complex, is dramatically reduced in dystrophin-deficient mdx mice and Duchenne muscular dystrophy patients. Recent evidence suggests that loss of nNOS in dystrophin-deficient muscle may contribute significantly to the progression of muscle pathology through a variety of mechanisms. To investigate whether nNOS plays a role in other forms of muscular dystrophy, we analyzed protein expression of nNOS in several sarcoglycan-deficient animal models of muscular dystrophy as well as patients with primary mutations in the sarcoglycan genes. Primary mutations in alpha-, beta-, delta-, and gamma-sarcoglycan result in autosomal recessive limb girdle muscular dystrophy (AR-LGMD). We report that loss of the sarcoglycan-sarcospan complex in muscle causes a dramatic reduction in the levels of nNOS expression at the membrane, even in the presence of normal dystrophin and syntrophin expression. Furthermore, we show that expression of three out of four sarcoglycans is not sufficient to maintain nNOS at the sarcolemma. Our data suggest that loss of nNOS may contribute to muscle pathology in AR-LGMD with primary mutations in the sarcoglycans.

Immunohistochemistry

Sarcolemma - enzymology

Membrane Glycoproteins - metabolism

Cytoskeletal Proteins - genetics

Humans

Male

Muscle, Skeletal - metabolism

Muscular Dystrophies - genetics

Neoplasm Proteins - metabolism

Muscular Dystrophy, Animal - pathology

Cytoskeletal Proteins - deficiency

Nitric Oxide Synthase Type I

Mice, Inbred mdx

Muscular Dystrophy, Animal - metabolism

Cytoskeletal Proteins - metabolism

Membrane Proteins - metabolism

Neoplasm Proteins - genetics

Dystrophin - metabolism

Cricetinae

Muscular Dystrophies - metabolism

Membrane Proteins - genetics

Mice, Inbred C57BL

Muscular Dystrophies - pathology

Blotting, Western

Membrane Glycoproteins - genetics

Carrier Proteins - genetics

Animals

Carrier Proteins - metabolism

Fluorescent Antibody Technique

Mice

Nitric Oxide Synthase - metabolism

Muscle, Skeletal - pathology

Mutation

Membrane Glycoproteins - deficiency

Details

Title: Subtitle: Loss of sarcolemma nNOS in sarcoglycan-deficient muscle
Creators: Rachelle H Crosbie - Howard Hughes Medical Institute, Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA
Rita Barresi
Kevin P Campbell
Resource Type: Journal article
Publication Details: The FASEB journal, Vol.16(13), pp.1786-1791
Publisher: United States
DOI: 10.1096/fj.02-0519com
PMID: 12409321
ISSN: 0892-6638
eISSN: 1530-6860
Grant note: R01 AR048179 / NIAMS NIH HHS DK25295 / NIDDK NIH HHS
Language: English
Date published: 11/2002
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984020885102771

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