title: Inactivation of creatine kinase by Adriamycin during interaction with horseradish peroxidase.
abstract: Oxidative damage of creatine kinase (CK) induced by Adriamycin((R)) (ADM) with peroxidase was investigated using horseradish peroxidase (HRP). ADM oxidatively inactivated CK during its interaction with HRP in the presence of H(2)O(2) (HRP-H(2)O(2)). The red color of ADM was lost during oxidation by HRP-H(2)O(2). Adding catalase stopped the color change of ADM induced by HRP-H(2)O(2), indicating that ADM was oxidized by HRP complex I or II. CK was inactivated readily, even when it was added to the reaction mixture containing colorless ADM. Some sulfhydryl groups of CK, which have an important role in its enzyme activity, were very sensitive to ADM activated by HRP-H(2)O(2), suggesting that inactivation of CK is due to oxidation of SH groups at the active center. Presumably, oxidative ADM quinone is involved dominantly in the inactivation of CK. Among the anthracycline drugs tested in this study, only ADM and epirubicin caused inactivation of CK and alcohol dehydrogenase and loss of the red color during oxidation by HRP-H(2)O(2).
authors.affiliation: Department of Biochemistry, Hokkaido College of Pharmacy, Otaru, Japan. miurat@hokuyakudai.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Miura
authors.forename: S
authors.initials: S
authors.lastname: Muraoka
authors.forename: Y
authors.initials: Y
authors.lastname: Fujimoto
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism / Q000494:pharmacology; D003402:Creatine Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D006735:Horseradish Peroxidase / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013053:Spectrophotometry; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D004791:Enzyme Inhibitors; D013438:Sulfhydryl Compounds; D004317:Doxorubicin; D006735:Horseradish Peroxidase; D003402:Creatine Kinase