Miura T, Muraoka S, Ogiso T
Department of Biochemistry, Hokkaido Institute of Pharmaceutical Sciences, Otaru, Japan.
Biol Pharm Bull. 1993 Jul;16(7):664-7. doi: 10.1248/bpb.16.664.
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.
当红细胞膜在铁蛋白存在的情况下与阿霉素（ADM）一起孵育时，会发生脂质过氧化反应，同时铁蛋白中的铁会释放出来。在脱铁铁蛋白存在的情况下，ADM不会引起脂质过氧化。去铁胺在铁蛋白存在的情况下抑制ADM诱导的脂质过氧化。这些结果表明脂质过氧化取决于铁从铁蛋白中的释放。即使铁蛋白中的铁含量非常低，ADM也能诱导脂质过氧化。超氧化物歧化酶、过氧化氢酶和羟自由基清除剂对脂质过氧化没有实质性影响，这表明过氧化反应与超氧化物、过氧化氢和羟自由基无关。铜蓝蛋白，一种铁氧化酶，显著抑制脂质过氧化，但不影响铁从铁蛋白中的释放。在铁蛋白存在的情况下，红细胞膜与ADM孵育期间很容易形成ADM-Fe(3+)结合的红细胞膜，而去铁胺从ADM-Fe(3+)结合膜中去除铁，这表明ADM-Fe(3+)复合物的铁部分暴露在膜表面。这些结果可能表明过氧化反应以位点特异性方式发生。
