ADRIAMYCIN-FE3-INDUCED MITOCHONDRIAL PROTEIN DAMAGE WITH LIPID-PEROXIDATION()

Exposure of mitochondria to adriamycin (ADM)-Fe3+ induced formation of thiobarbituric acid reactive substances and fluorescent substances. B utylated hydroxytoluene (BHT) and the water soluble vitamin E analogue , trolox, not only strongly inhibited fluorescence formation but also mitochondrial lipid peroxidation. Sodium dodecyl sulfate-polyacrylamid e gel electrophoresis indicated the formation of high molecular weight proteins when mitochondria were exposed to ADM-Fe3+. A mitochondrial protein with a molecular weight of approximately 30 kDa was very sensi tive to ADM-Fe3+. BHT and trolox strongly inhibited mitochondrial prot ein cross-linking, indicating that the protein modification was due to ADM-Fe3+-induced lipid peroxidation. In addition, the susceptibility of ADM-Fe3+-exposed mitochondrial protein to proteases was unchanged. Bovine serum albumin (BSA) inhibited ADM-Fe3+-induced mitochondrial li pid peroxidation. Fluorescence emmited from BSA was detected during AD M-Fe3+-induced mitochondrial lipid peroxidation, and BHT strongly inhi bited the oxidative modification of BSA. These results suggest that th e oxidative modification of mitochondrial proteins and BSA is due to A DM-Fe3+-induced lipid peroxidation.