The susceptibility of muscle cells to oxidative stress is independent of nitric oxide synthase expression

• Published in: Muscle & nerve Vol. 24; no. 4; pp. 502 - 511
• Main Authors: Zhuang, Weiyun, Eby, Josh C., Cheong, Monica, Mohapatra, Pramit K., Bredt, David S., Disatnik, Marie-Hélène, Rando, Thomas A.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.04.2001; Wiley
• Subjects: Animals; Biological and medical sciences; Cell Differentiation; Cells, Cultured; Disease Models, Animal; Diseases of striated muscles. Neuromuscular diseases; Dose-Response Relationship, Drug; dystrophin; Enzyme Inhibitors - pharmacology; free radical; Gene Expression - drug effects; mdx; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred mdx; Mice, Knockout; Muscle, Skeletal - cytology; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; muscular dystrophy; Muscular Dystrophy, Animal - genetics; Muscular Dystrophy, Animal - metabolism; Myofibrils - drug effects; Myofibrils - metabolism; Neurology; nitric oxide; nitric oxide synthase; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase - deficiency; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type I; Oxidants - pharmacology; oxidative stress; Oxidative Stress - physiology; Reactive Oxygen Species - metabolism; Transfection; Redox state; Oxidative stress; Neuromuscular diseases; Nervous system diseases; Enzyme; Pathogenesis; Rodentia; Gene overexpression; Gene expression; Striated muscle; Muscular dystrophy; Nitric-oxide synthase; Free radical; Genetic disease; Vertebrata; Mammalia; Mouse; Animal; Nitric oxide; Oxidoreductases
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.1033

The free radical, nitric oxide (NO·), has been implicated in the pathogenesis of muscular dystrophies because the enzyme, nitric oxide synthase (NOS), which produces NO·, binds to the dystrophin–glycoprotein complex (DGC). In various studies of tissue samples from human and animal muscular dystrophies due to DGC defects, correlations between reductions of NOS activity and disease severity have been reported. To test for any direct effect of NOS expression on muscle cell susceptibility, we examined muscle cells in vitro under conditions of experimentally altered NOS activity. There were no differences in susceptibility to oxidative stress between differentiated myotube cultures from wild‐type and from neuronal NOS (nNOS)‐deficient mice. Likewise, pharmacological inhibition of NOS did not alter cellular susceptibility to oxidative challenges. Overexpression of NOS neither enhanced nor diminished cellular susceptibility to oxidative stress. Finally, we assessed the effect of NOS overexpression on myotube cultures from dystrophin‐deficient (mdx) mice. NOS protein was localized to both membrane and cytosolic compartments in the transduced cells. Still, no difference in susceptibility to oxidative stress was found between the NOS‐overexpressing cells and control cells. These data suggest that muscle cell susceptibility to oxidative challenges is independent of the level of NOS expression. Therefore, any role NO· may play in the pathogenesis of muscular dystrophies is likely to be independent of its effect on the redox state of the cell. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 502–511, 2001