ADRIAMYCIN-FE3-INDUCED INACTIVATION OF RAT-HEART MITOCHONDRIAL CREATINE-KINASE - SENSITIVITY TO LIPID-PEROXIDATION()

Adriamycin (ADM)-Fe3+ caused inactivation of rat heart mitochondrial c reatine kinase (CK) with lipid peroxidation. Superoxide dismutase, cat alase and hydroxyl radical scavengers were without effect on the CK in activation and the lipid peroxidation induced by ADM-Fe3+, indicating the lack of involvement of superoxide, hydrogen peroxide or hydroxyl r adicals in these reactions. The antioxidant butylated hydroxytoluene s trongly inhibited not only lipid peroxidation but also CK inactivation , indicating that mitochondrial CK was inactivated with lipid peroxida tion. Reduced glutathione and dithiothreitol (DTT) prevented CK inacti vation 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 CR inacti vation was due to oxidative damage of sulfhydryl groups. In contrast, mitochondrial protein SH groups were not attacked via ADM-Fe3+-induced lipid peroxidation. Thus, the SH groups in mitochondrial CK are very susceptible to ADM-Fe3+-induced lipid peroxidation.