Adriamycin-induced lipid peroxidation of erythrocyte membranes in the presence of ferritin and the inhibitory effect of ceruloplasmin.
When erythrocyte membranes were incubated with adriamycin (ADM) in the presence of ferritin, lipid peroxidation occurred with release of iron from the ferritin. In the presence of apoferritin, ADM did not cause lipid peroxidation. Deferoxamine inhibited the ADM-induced lipid peroxidation in the presence of ferritin. These results indicate that lipid peroxidation depends upon the release of iron from ferritin. Even when the iron content in ferritin was very low, ADM could induce lipid peroxidation. Superoxide dismutase, catalase and hydroxyl radical scavengers did not substantially affect lipid peroxidation, indicating that the peroxidation reaction was independent of superoxide, H2O2 and hydroxyl radicals. Ceruloplasmin, a ferroxidase, markedly inhibited lipid peroxidation but did not affect the release of iron from ferritin. ADM-Fe(3+)-binding erythrocyte membranes were readily formed during the incubation of erythrocyte membranes with ADM in the presence of ferritin, and deferoxamine removed iron from the ADM-Fe(3+)-binding membranes, indicating that the iron moiety of the ADM-Fe(3+) complex is exposed at the membrane surface. These results may suggest that the peroxidation reaction occurs in a site-specific manner.
Miura
T
T
Department of Biochemistry, Hokkaido Institute of Pharmaceutical Sciences, Otaru, Japan.
Muraoka
S
S
Ogiso
T
T
D000818:Animals; D002374:Catalase / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D002570:Ceruloplasmin / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005290:Ferric Compounds / Q000378:metabolism; D005293:Ferritins / Q000494:pharmacology*; D016166:Free Radical Scavengers; D015227:Lipid Peroxidation / Q000187:drug effects*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
D005290:Ferric Compounds; D016166:Free Radical Scavengers; D004317:Doxorubicin; D005293:Ferritins; D002374:Catalase; D013482:Superoxide Dismutase; D002570:Ceruloplasmin; D003676:Deferoxamine