Sensitivity of FRDA lymphoblasts to salts of transition metal ions.
Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease resulting from decreased expression of the nuclear-encoded mitochondrial protein, frataxin. FRDA patients have characteristic iron deposits and dysfunction of mitochondrial enzymes in the heart. Inactivation of the frataxin homologue in yeast causes dysregulation of both mitochondrial iron levels and iron export. Previously, we have observed sensitivity of FRDA fibroblasts to FeCl3 and hydrogen peroxide, results consistent with the hypothesis that FRDA cells may experience increased Fenton chemistry. To determine whether the sensitivity of FRDA cells to transition metal ions is a general or specific property, we have compared the sensitivity of lymphoblasts from FRDA patients and healthy controls to the transition metal salts CoCl2, CuSO4 FeCl3 FeSO4, MnCl2, and ZnCl2. FRDA lymphoblasts were significantly more sensitive to FeCl3 and MnCl2 than control cells. However, there were no significant differences observed in sensitivity to CoCl2, CuSO4, FeSO4 and ZnCl2 in the concentration ranges studied. Thus, the sensitivity of FRDA lymphoblasts exposed to transition metals appears to be specific, and could be relevant to the pathophysiological mechanism, which is discussed.
Department of Molecular Biosciences, University of California, Davis 95616, USA.
A
A
Wong
J
J
Yang
S
S
Danielson
C
C
Gellera
F
F
Taroni
G
G
Cortopassi
D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D019327:Copper Sulfate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005621:Friedreich Ataxia / Q000188:drug therapy*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007477:Ions / Q000494:pharmacology*; D015636:Magnesium Chloride / Q000494:pharmacology; D017895:Manganese Compounds / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012492:Salts / Q000494:pharmacology*; D017967:Zinc Compounds / Q000494:pharmacology
D002712:Chlorides; D005290:Ferric Compounds; D007477:Ions; D017895:Manganese Compounds; D017382:Reactive Oxygen Species; D012492:Salts; D017967:Zinc Compounds; D015636:Magnesium Chloride; D003035:Cobalt; C024823:ferric sulfate; C016837:zinc chloride; D006861:Hydrogen Peroxide; C018021:cobaltous chloride; D019327:Copper Sulfate; C025340:manganese chloride; C024555:ferric chloride