Effect of Zinc and Copper on the Interaction of Daunorubicin with Cardiac Myosin

Abstract

Daunorubicin (DNR) is an anthracyline antibiotic which induces a well-described but incompletely understood cardiac toxicity. In this study, a direct action of DNR on the major contractile protein, cardiac myosin (CM), was described utilizing the fluorescence spectroscopy. The quenching mechanism was suggested to be static quenching according to the fluorescence measurement. In particular, the effects of common ions on the binding constants of DNR with CM were also investigated under physiological conditions, and the quenching constant K(SV) and binding constant K(LB) were obtained at room temperature. These data proved that Zn2+ and/or Cu2+ potentiated quenching fluorescence intensity of DNR-CM complex. Moreover, the normal ratio of Zn2+ to Cu2+ was able to competitively inhibit the binding interaction of DNR with CM, which might contribute to exert the most significant cardioprotective effect and guarantee the contractile machinery of cardiac muscle.