Evidence against increased oxidative stress in fibroblasts from patients with non-superoxide-dismutase-1 mutant familial amyotrophic lateral sclerosis

Fibroblasts were cultured from 5 unrelated familial amyotrophic lateral sclerosis (FALS) patients and from healthy control subjects. In parallel, fibroblasts were examined for signs of abnormal oxidative stress by study of reactive oxygen species metabolism and, concurrently, leukocyte DNA from the same patients was examined for superoxide dismutase 1 (SOD1) mutations. The endogenous production of reactive oxygen species was assessed by following the menadione-induced reduction of oxidized cytochrome c, added to the medium. FALS and control fibroblasts exhibited the same rate of metabolism. Also levels of thiobarbituric- acid-re active species (TEARS), a marker of lipid peroxidation, were similar in fibroblasts from either group. The search for SOD1 mutations by linkage study and cycle sequencing proved negative. We did not find evidence for SOD1 mutations by either method of study. Our results provide no evidence for increased oxidative stress in fibroblasts from non-SOD1 mutant FALS.