Oxidative stress and antioxidant enzyme upregulation in SOD1-G93A mouse skeletal muscle.
Amyotrophic lateral sclerosis (ALS) is caused by motor neuron loss in the spinal cord, but the mechanisms responsible are not known. Ubiquitous transgenic overexpression of copper/zinc superoxide dismutase (SOD1) mutations causing familial ALS (SOD1mut) leads to an ALS phenotype in mice; however, restricted expression of SOD1mut in neurons alone is not sufficient to cause this phenotype, suggesting that non-neuronal SOD1mut expression is also required for disease manifestation. Recently, several investigators have suggested that SOD1mut -mediated oxidative stress in skeletal muscle may contribute to ALS pathogenesis. The purpose of this study was to examine oxidative stress and antioxidant enzyme adaptation in 95-day-old SOD1-G93A skeletal muscle. We observed significant elevations in both malondialdehyde (22% and 31% in red and white gastrocnemius, respectively) and protein carbonyls (53% in red gastrocnemius) in SOD1-G93A mice. Copper/zinc SOD activity was higher in red and white SOD1-G93A gastrocnemius (7- and 10-fold, respectively), as was manganese SOD (4- and 5-fold, respectively) and catalase (2- and 2.5-fold, respectively). Taken together, our data demonstrate oxidative stress and compensatory antioxidant enzyme upregulation in SOD1-G93A skeletal muscle.
Department of Medical Sciences, McMaster University, Hamilton, Ontario, Canada.
Douglas J
DJ
Mahoney
Jan J
JJ
Kaczor
Jacqueline
J
Bourgeois
Nobuo
N
Yasuda
Mark A
MA
Tarnopolsky
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000201:enzymology; D018485:Muscle Fibers, Skeletal / Q000201:enzymology; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology*; D018384:Oxidative Stress / Q000502:physiology*; D010641:Phenotype; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation / Q000502:physiology
D000975:Antioxidants; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1