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J. Biol. Chem., Vol. 260, Issue 6, 3275-3280, Mar, 1985
Ferritin and superoxide-dependent lipid peroxidation
CE Thomas, LA Morehouse and SD Aust
Ferritin was found to promote the peroxidation of phospholipid liposomes,
as evidenced by malondialdehyde formation, when incubated with xanthine
oxidase, xanthine, and ADP. Activity was inhibited by superoxide dismutase
but markedly stimulated by the addition of catalase. Xanthine
oxidase-dependent iron release from ferritin, measured
spectrophotometrically using the ferrous iron chelator 2,2'- dipyridyl, was
also inhibited by superoxide dismutase, suggesting that superoxide can
mediate the reductive release of iron from ferritin. Potassium superoxide
in crown ether also promoted superoxide dismutase- inhibitable release of
iron from ferritin. Catalase had little effect on the rate of iron release
from ferritin; thus hydrogen peroxide appears to inhibit lipid peroxidation
by preventing the formation of an initiating species rather than by
inhibiting iron release from ferritin. EPR spin trapping with
5,5-dimethyl-1-pyrroline-N-oxide was used to observe free radical
production in this system. Addition of ferritin to the xanthine oxidase
system resulted in loss of the superoxide spin trap adduct suggesting an
interaction between superoxide and ferritin. The resultant spectrum was
that of a hydroxyl radical spin trap adduct which was abolished by the
addition of catalase. These data suggest that ferritin may function in vivo
as a source of iron for promotion of superoxide-dependent lipid
peroxidation. Stimulation of lipid peroxidation but inhibition of hydroxyl
radical formation by catalase suggests that, in this system, initiation is
not via an iron-catalyzed Haber-Weiss reaction.

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Copyright © 1985 by the American Society for Biochemistry and Molecular Biology.
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