1. Nitric oxide synthase in muscular dystrophies: a re-evaluation.
- Author
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Buchwalow IB, Minin EA, Müller FU, Lewin G, Samoilova VE, Schmitz W, Wellner M, Hasselblatt M, Punkt K, Müller-Werdan U, Demus U, Slezak J, Koehler G, and Boecker W
- Subjects
- 3',5'-Cyclic-GMP Phosphodiesterases metabolism, Adult, Arginase metabolism, Blotting, Western, Cell Survival physiology, Child, Preschool, Cyclic AMP Response Element-Binding Protein genetics, Cyclic AMP Response Element-Binding Protein physiology, Female, Fluorescent Antibody Technique, Guanylate Cyclase metabolism, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Isoenzymes biosynthesis, Male, Muscle, Skeletal enzymology, Muscle, Skeletal metabolism, Muscular Dystrophy, Duchenne enzymology, Nitric Oxide physiology, Oxidative Stress physiology, RNA biosynthesis, RNA isolation & purification, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction physiology, Tyrosine analogs & derivatives, Tyrosine pharmacology, Muscular Dystrophies enzymology, Nitric Oxide Synthase metabolism
- 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.
- Published
- 2006
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