The effect of doxorubicin on the transport of pyruvate in rat-heart mitochondria.
The effect of doxorubicin on the transport of pyruvate in rat-heart mitochondria was studied. It was found that the rate of pyruvate transport is inhibited by doxorubicin, half maximal inhibition being obtained at concentration of 125 microM of the drug. The inhibition is not due to a change in the transmembrane delta pH nor does it depend on an interaction of doxorubicin with thyol groups of the pyruvate carrier. Doxorubicin also inhibits the pyruvate dependent oxygen uptake and the specific binding of alpha-cyanocinnamate to mitochondria. It is proposed that doxorubicin affects the pyruvate transport by interacting with cardiolipin molecules surrounding the pyruvate carrier in the mitochondrial membrane.
Paradies
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Department of Biochemistry and Molecular Biology, University of Bari, Italy.
Ruggiero
F M
FM
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D002934:Cinnamates / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000187:drug effects*; D027501:Monocarboxylic Acid Transporters; D010101:Oxygen Consumption / Q000187:drug effects; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid; D051381:Rats
D002934:Cinnamates; D027501:Monocarboxylic Acid Transporters; D011773:Pyruvates; C018253:alpha-cyanocinnamate; D004317:Doxorubicin; D019289:Pyruvic Acid