title: Nitric oxide synthase in muscular dystrophies: a re-evaluation.
abstract: Duchenne and Becker muscular dystrophies (DMD and BMD) are associated with decreased total nitric oxide (NO). However, mechanisms leading to NO deficiency with consequent muscle-cell degeneration remain unknown. To address this issue, we examined skeletal muscles of DMD and BMD patients for co-expression of NO synthase (NOS) with nitrotyrosine and transcription factor CREB, as well as with enzymes engaged in NO signaling. Employing immunocytochemical labeling, Western blotting and RT-PCR, we found that, in contrast to the most commonly accepted view, neuronal NOS was not restricted to the sarcolemma and that muscles of DMD and BMD patients retained all three NOS isoforms with an up-regulation of the inducible NOS isoform, CREB and nitrotyrosine. We suggest that enhanced nitrotyrosine immunostaining in muscle fibers as well as in the vasculature of DMD and BMD specimens reflects massive oxidative stress, resulting in withdrawal of NO from its regular physiological course via the scavenging actions of superoxides.
authors.affiliation: Gerhard Domagk Institute of Pathology, University of Muenster, Domagkstr. 17, 48149, Muenster, Germany. buchwalo@uni-muenster.de
authors.forename: Igor B
authors.initials: IB
authors.lastname: Buchwalow
authors.forename: Evgeny A
authors.initials: EA
authors.lastname: Minin
authors.forename: Frank-Ulrich
authors.initials: FU
authors.lastname: Müller
authors.forename: Geertje
authors.initials: G
authors.lastname: Lewin
authors.forename: Vera E
authors.initials: VE
authors.lastname: Samoilova
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Schmitz
authors.forename: Maren
authors.initials: M
authors.lastname: Wellner
authors.forename: Martin
authors.initials: M
authors.lastname: Hasselblatt
authors.forename: Karla
authors.initials: K
authors.lastname: Punkt
authors.forename: Ursula
authors.initials: U
authors.lastname: Müller-Werdan
authors.forename: Uta
authors.initials: U
authors.lastname: Demus
authors.forename: Jan
authors.initials: J
authors.lastname: Slezak
authors.forename: Gabriele
authors.initials: G
authors.lastname: Koehler
authors.forename: Werner
authors.initials: W
authors.lastname: Boecker
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D000328:Adult; D001119:Arginase / Q000378:metabolism; D015153:Blotting, Western; D002470:Cell Survival / Q000502:physiology; D002675:Child, Preschool; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism; D009136:Muscular Dystrophies / Q000201:enzymology*; D020388:Muscular Dystrophy, Duchenne / Q000201:enzymology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D007527:Isoenzymes; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D012313:RNA; D019001:Nitric Oxide Synthase; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D001119:Arginase; D006162:Guanylate Cyclase