title: Role of oxidative damage in Friedreich's ataxia.
abstract: Plasma malondialdehyde (MDA) levels were raised in Friedreich's ataxia (FRDA) patients. These levels correlated with increasing age and disease duration, suggesting lipid peroxidation increased with disease progression. Using fibroblasts from FRDA patients we observed that GSH levels and aconitase activities were normal, suggesting their antioxidant status was unchanged. When exposed to various agents to increase free radical generation we observed that intracellular superoxide generation induced by paraquat caused enhanced oxidative damage. This correlated with the size of the GAA1 expansion, suggesting decreased frataxin levels may render the cells more vulnerable to mild oxidative stress. More severe oxidative stress induced by hydrogen peroxide caused increased cell death in FRDA fibroblasts but was not significantly different from control cells. We propose that abnormal respiratory chain function and iron accumulation may lead to a progressive increase in oxidative damage, but increased sensitivity to free radicals may not require detectable respiratory chain dysfunction.
authors.affiliation: Department of Clinical Neuroscience, Royal Free and University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, United Kingdom.
authors.forename: J L
authors.initials: JL
authors.lastname: Bradley
authors.forename: S
authors.initials: S
authors.lastname: Homayoun
authors.forename: P E
authors.initials: PE
authors.lastname: Hart
authors.forename: A H V
authors.initials: AH
authors.lastname: Schapira
authors.forename: J M
authors.initials: JM
authors.lastname: Cooper
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015415:Biomarkers / Q000097:blood; D002470:Cell Survival / Q000187:drug effects; D002648:Child; D002712:Chlorides; D005290:Ferric Compounds / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005621:Friedreich Ataxia / Q000097:blood / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008315:Malondialdehyde / Q000097:blood*; D018384:Oxidative Stress; D012016:Reference Values
chemical_list: D015415:Biomarkers; D002712:Chlorides; D005290:Ferric Compounds; D008315:Malondialdehyde; D000154:Aconitate Hydratase; D005978:Glutathione; C024555:ferric chloride