Superoxide Dismutase Concentration and Activity in Familial Amyotrophic Lateral Sclerosis
Article first published online: 23 NOV 2002
Journal of Neurochemistry
Volume 64, Issue 5, pages 2366–2369, May 1995
How to Cite
Bowling, A. C., Barkowski, E. E., McKenna-Yasek, D., Sapp, P., Horvitz, H. R., Beal, M. F. and Brown, R. H. (1995), Superoxide Dismutase Concentration and Activity in Familial Amyotrophic Lateral Sclerosis. Journal of Neurochemistry, 64: 2366–2369. doi: 10.1046/j.1471-4159.1995.64052366.x
- Issue published online: 23 NOV 2002
- Article first published online: 23 NOV 2002
- Resubmitted manuscript received January 23, 1995; accepted January 27, 1995.
- Amyotrophic lateral sclerosis;
- Free radicals;
- Oxidative damage;
- Superoxide dismutase
Abstract: Some cases of autosomal-dominant familial amyotrophic lateral sclerosis (FALS) have been associated with mutations in SOD1, the gene that encodes Cu/Zn superoxide dismutase (Cu/Zn SOD). We determined the concentrations (µg of Cu/Zn SOD/mg of total protein), specific activities (U/µg of total protein), and apparent turnover numbers (U/µmol of Cu/Zn SOD) of Cu/Zn SOD in erythrocyte lysates from patients with known SOD1 mutations. We also measured the concentrations and activities of Cu/Zn SOD in FALS patients with no identifiable SOD1 mutations, sporadic ALS (SALS) patients, and patients with other neurologic disorders. The concentration and specific activity of Cu/Zn SOD were decreased in all patients with SOD1 mutations, with mean reductions of 51 and 46%, respectively, relative to controls. In contrast, the apparent turnover number of the enzyme was not altered in these patients. For the six mutations studied, there was no correlation between enzyme concentration or specific activity and disease severity, expressed as either duration of disease or age of onset. No significant alterations in the concentration, specific activity, or apparent turnover number of Cu/Zn SOD were detected in the FALS patients with no identifiable SOD1 mutations, SALS patients, or patients with other neurologic disorders. That Cu/Zn SOD concentration and specific activity are equivalently reduced in erythrocytes from patients with SOD1 mutations suggests that mutant Cu/Zn SOD is unstable in these cells. That concentration and specific activity do not correlate with disease severity suggests that an altered, novel function of the enzyme, rather than reduction of its dismutase activity, may be responsible for the pathogenesis of FALS.