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Microsomal lipid peroxidation. I. Characterization of the role of iron and NADPH

Journal Article · · Mol. Pharmacol.; (United States)
OSTI ID:6122268
The NADPH/iron-dependent peroxidation of lipids in rat liver microsomes was found to depend on the presence of free ferrous iron. High concentrations of Fe/sup 2 +/ initiated microsomal lipid peroxidation at an initial rate which was independent of NADPH. With Fe/sup 3 +/, lower Fe/sup 2 +/ concentrations, or longer incubation times, NADPH stimulated microsomal lipid peroxidation and this stimulation was blocked by cytochrome c. NADPH did not induce peroxidation in the absence of iron, nor did ferric iron in the absence of NADPH. Thus the role of NADPH appears to be maintenance of iron in the reduced Fe/sup 2 +/ state. Complete chelation of iron by EDTA completely inhibited peroxidation. Preincubation of microsomes in the absence of iron did not enhance the rate of peroxidation upon subsequent addition of iron, suggesting that iron acts by initiating peroxidative decomposition of membrane lipids rather than by catalyzing the breakdown of preformed hydroperoxides. Ascorbate stimulated iron-induced liposomal peroxidation but had no effect in the absence of iron.
Research Organization:
Univ. of Rochester, NY
OSTI ID:
6122268
Journal Information:
Mol. Pharmacol.; (United States), Journal Name: Mol. Pharmacol.; (United States) Vol. 17; ISSN MOPMA
Country of Publication:
United States
Language:
English