Partial loss of NADPH-diaphorase/nitric oxide synthase-complex in amyotrophic lateral sclerosis and human type-II myofiber atrophy.
To substantiate the role of nitric oxide synthase type-I (NOS-I) in neurogenic muscular disorders we investigated human biopsy samples of type-II fiber atrophy and amyotrophic lateral sclerosis (ALS) by NOS-I immunoreactivity (-IR), NOS-associated NADPH-dependent diaphorase activity (NOSaD) and Western blot analysis. In type-II atrophy, loss of NOSaD and reduced NOS-I-IR was apparent in atrophic myofibers. In atrophic fiber groups lacking NOSaD, both NOS-I and dystrophin-IR was decreased while sarcolemmal beta-dystroglycan- and adhalin-IR (markers of the sarcolemmal dystrophin-glycoprotein complex) was normal. In ALS, groups of scattered angulated atrophic fibers revealed partial loss of NOS-I-IR/NOSaD. Atrophied fibers of either type-I or type-II thus revealed differential sarcolemmal NOS/NOSaD pattern thereby reflecting myopathological alterations of the NO-system in human type-II atrophy and ALS.
Schoser
B G
BG
Department of Neurology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. schoser@uke.uni-hamburg.de
Lück
G
G
Blottner
D
D
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology*; D001706:Biopsy; D015153:Blotting, Western; D003598:Cytoskeletal Proteins / Q000378:metabolism; D049030:Dystroglycans; D016189:Dystrophin / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology*; D009133:Muscular Atrophy / Q000201:enzymology*; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D049031:Sarcoglycans
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D016189:Dystrophin; D008562:Membrane Glycoproteins; D049031:Sarcoglycans; D049030:Dystroglycans; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase