Differential response of iron metabolism to oxidative stress generated by antimycin A and nitrofurantoin.
The close interrelationship of oxidative stress and iron is evident by the influence of intracellular reactive oxygen species on iron metabolism. Oxygen radicals can lead to release of iron from iron-sulfur proteins and ferritin, and can damage iron-containing enzymes such as mitochondrial aconitase. Treatment of HepG2 human hepatoma cells with antimycin A has two effects relating to iron depending on the concentrations of antimycin A: increase of the labile iron pool and stimulation of non-transferrin-bound iron uptake. Whereas the first could also be generated with nitrofurantoin, the stimulation of non-transferrin-bound iron uptake was only seen with antimycin A and needed considerably higher concentrations. Pretreatment of the cells with ebselen, which scavenges peroxides, reverted only the effect of nitrofurantoin on the labile iron pool. Depletion with iron chelators before or after treatment with antimycin A diminished the stimulation of non-transferrin-bound iron uptake. We conclude that the generation of oxygen radicals in the mitochondria leads to the liberation of iron from mitochondrial enzymes, which enters the labile iron pool. But high concentrations of antimycin A leading to the stimulation of non-transferrin-bound iron uptake is possibly not related to the inhibition of the respiratory chain.
Sturm
Brigitte
B
Department of Medical Chemistry, Medical University of Vienna, Waehringerstrasse 10, 1090 Vienna, Austria.
Twaroch
Teresa
T
Knapitsch
Birgit
B
Czingraber
Sylvia
S
Ternes
Nina
N
Goldenberg
Hans
H
Scheiber-Mojdehkar
Barbara
B
D000968:Antimycin A / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D009582:Nitrofurantoin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*
D007502:Iron Chelating Agents; D000968:Antimycin A; D009582:Nitrofurantoin; D007501:Iron