Document Detail


The Adriamycin (doxorubicin)-induced inactivation of cytochrome c oxidase depends on the presence of iron or copper.
MedLine Citation:
PMID:  2543148     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. It was confirmed that Adriamycin (doxorubicin) inactivates cytochrome c oxidase upon incubation. However, further investigation shows that this inactivation is strongly dependent upon the presence of Fe3+ and Cu2+. Trace amounts of these transition metal ions, present in phosphate and Tris buffers, bind strongly to the Adriamycin and the complex formed is responsible for the inactivation of cytochrome c oxidase. No Adriamycin-induced inactivation of cytochrome c oxidase occurred in the presence of EDTA or in phosphate buffers purified on a cation exchange column to remove trace metals. 2. The metal ion-induced inactivation of cytochrome c oxidase by Adriamycin results in significant decreases in both the maximum velocity and the Michaelis constant. The degree of inactivation is strongly dependent on the Fe3+ concentration. 3. Cardiolipin partially protects against cytochrome c oxidase inactivation, presumably by binding to the cytochrome c oxidase, whereas catalase or superoxide dismutase partially protect by scavenging damaging reactive oxygen species generated within a Fe3+-Adriamycin-enzyme complex.
Authors:
B B Hasinoff; J P Davey; P J O'Brien
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Xenobiotica; the fate of foreign compounds in biological systems     Volume:  19     ISSN:  0049-8254     ISO Abbreviation:  Xenobiotica     Publication Date:  1989 Feb 
Date Detail:
Created Date:  1989-07-03     Completed Date:  1989-07-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1306665     Medline TA:  Xenobiotica     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  231-41     Citation Subset:  IM    
Affiliation:
Memorial University of Newfoundland, St. John's, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Binding, Competitive
Cardiolipins / pharmacology
Cattle
Copper / pharmacology*
Cytochrome c Group / pharmacology
Dithiothreitol / pharmacology
Doxorubicin / pharmacology*
Egtazic Acid / pharmacology
Electron Transport Complex IV / antagonists & inhibitors*
Enzyme Activation / drug effects
Enzyme Repression / drug effects
Glutathione / pharmacology
Iron / pharmacology*
Kinetics
Chemical
Reg. No./Substance:
0/Cardiolipins; 0/Cytochrome c Group; 23214-92-8/Doxorubicin; 3483-12-3/Dithiothreitol; 67-42-5/Egtazic Acid; 70-18-8/Glutathione; 7439-89-6/Iron; 7440-50-8/Copper; EC 1.9.3.1/Electron Transport Complex IV

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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