Interaction of adriamycin in vitro with cardiac myofibrillar proteins.
Binding of the anthracycline antibiotic doxorubicin [Adriamycin (ADR)] to selected cardiac muscle contractile proteins was determined in purified canine heart actin and alpha-actinin. Adriamycin binding to these proteins in solution was measured by equilibrium dialysis and gel filtration with [14C]-labeled ADR. Adriamycin did not bind when its primary amino group was blocked. Adriamycin binding did not affect actin polymerization as detected by viscometry. Viewed under the electron microscope, however, ADR promoted formation of distinct actin filaments in the presence of microM amounts of ATP without K+ and MG++. Adriamycin-induced actin microfilaments were thicker (120 A) than those of F-actin controls (70 A) and stimulated myosin-ATPase to higher levels than the F-actin controls. It appears that ADR has a direct effect on the biophysical and biochemical properties of heart myofibril proteins in vitro.
D000185:Actinin / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002846:Chromatography, Affinity; D004285:Dogs; D004317:Doxorubicin / Q000378:metabolism* / Q000633:toxicity; D008854:Microscopy, Electron; D009124:Muscle Proteins / Q000378:metabolism*; D009210:Myofibrils / Q000187:drug effects / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism*; D014783:Viscosity
D000199:Actins; D009124:Muscle Proteins; D000185:Actinin; D004317:Doxorubicin; D009218:Myosins