Adriamycin-Fe(3+)-induced inactivation of rat heart mitochondrial creatine kinase: sensitivity to lipid peroxidation.
Adriamycin (ADM)-Fe3+ caused inactivation of rat heart mitochondrial creatine kinase (CK) with lipid peroxidation. Superoxide dismutase, catalase and hydroxyl radical scavengers were without effect on the CK inactivation and the lipid peroxidation induced by ADM-Fe3+, indicating the lack of involvement of superoxide, hydrogen peroxide or hydroxyl radicals in these reactions. The antioxidant butylated hydroxytoluene strongly inhibited not only lipid peroxidation but also CK inactivation, indicating that mitochondrial CK was inactivated with lipid peroxidation. Reduced glutathione and dithiothreitol (DTT) prevented CK inactivation without inhibiting lipid peroxidation. The CK activity of 5,5'-dithiobis-(nitorobenzoic acid)-treated mitochondria exposed to ADM-Fe3+ was partially reversed by addition of DTT, indicating that CK inactivation was due to oxidative damage of sulfhydryl groups. In contrast, mitochondrial protein SH groups were not attacked via ADM-Fe(3+)-induced lipid peroxidation. Thus, the SH groups in mitochondrial CK are very susceptible to ADM-Fe(3+)-induced lipid peroxidation.
Hokkaido Institute of Pharmaceutical Sciences, Japan.
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Miura
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Muraoka
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Ogiso
D000818:Animals; D003402:Creatine Kinase / Q000037:antagonists & inhibitors*; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D016166:Free Radical Scavengers; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism
D016166:Free Radical Scavengers; D009942:Organometallic Compounds; D013438:Sulfhydryl Compounds; C041415:doxorubicin-iron complex; D004317:Doxorubicin; D004228:Dithionitrobenzoic Acid; D007501:Iron; D003402:Creatine Kinase; D004229:Dithiothreitol