Oxidative stress and antioxidant enzyme upregulation in SOD1-G93A mouse skeletal muscle

Muscle Nerve. 2006 Jun;33(6):809-16. doi: 10.1002/mus.20542.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Enzyme Activation
  • Gene Expression Regulation, Enzymologic
  • Male
  • Mice
  • Mice, Transgenic
  • Mitochondria / enzymology
  • Muscle Fibers, Skeletal / enzymology
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / enzymology*
  • Oxidative Stress / physiology*
  • Phenotype
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / metabolism*
  • Superoxide Dismutase-1
  • Up-Regulation / physiology


  • Antioxidants
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1