title: Increased sensitivity of fibroblasts from amyotrophic lateral sclerosis patients to oxidative stress.
abstract: Although the cause of amyotrophic lateral sclerosis (ALS) is unkNown, free radical toxicity is thought to play a pathogenic role. We investigated whether cells from ALS patients are more vulnerable to exogenously induced oxidative stress than cells from controls. We therefore studied the sensitivity of fibroblasts from patients with sporadic ALS (SALS), and from patients with familial ALS (FALS) associated with copper/zinc superoxide dismutase (Cu/ZnSOD) mutations (SOD1-FALS), to the free radical-generating agents 3-morpholinosydnonimine (SIN-1) and hydrogen peroxide (H2O2), and to serum withdrawal. SOD1-FALS and SALS fibroblasts were significantly more sensitive than controls to SIN-1 but not to serum withdrawal. In addition, SOD1-FALS fibroblasts were more sensitive to H2O2 than SALS fibroblasts and than fibroblasts of controls. These results suggest that the mechanism underlying both SOD1-FALS and SALS jeopardizes the cell's defense against free radical stress, and that SOD1-FALS cells are particularly sensitive to H2O2. The latter finding is compatible with biochemical data on the increased affinity of the mutated Cu/ZnSOD for H2O2.
authors.affiliation: Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Aguirre
authors.forename: L
authors.initials: L
authors.lastname: Van Den Bosch
authors.forename: K
authors.initials: K
authors.lastname: Goetschalckx
authors.forename: P
authors.initials: P
authors.lastname: Tilkin
authors.forename: G
authors.initials: G
authors.lastname: Mathijs
authors.forename: J J
authors.initials: JJ
authors.lastname: Cassiman
authors.forename: W
authors.initials: W
authors.lastname: Robberecht
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007700:Kinetics; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018384:Oxidative Stress; D017354:Point Mutation; D012016:Reference Values; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D004791:Enzyme Inhibitors; C002385:linsidomine; D006861:Hydrogen Peroxide; D008981:Molsidomine; D013482:Superoxide Dismutase