The effect of adriamycin and duramycin on calcium translocation in liposome systems modeled on the inner mitochondrial membrane.
Adriamycin (doxorubicin, AdM) is a potent antineoplastic agent which binds specifically and with high affinity to the acidic phospholipid cardiolipin (CL) [Goormaghtigh et al. (1980) Biochim. Biophys. Acta 597, 1]. Duramycin (DM), a polypeptide antibiotic, has been reported to interact selectively with phosphatidylethanolamine (PE) and monogalactosyldiacylglycerol [Navarro et al. (1985) Biochemistry 24, 4645]. The selectivity of DM-PE interaction was confirmed. AdM and DM were then used to explore the roles of CL and PE in Ca2+ translocation in a phosphatidylcholine (PC)/PE/CL liposome system modeled on the inner mitochondrial membrane with the following results: (i) AdM (100-400 microM) altered Ca2+ uptake by PC/PE/CL (4/4/1, mol/mol) liposomes in a concentration-dependent fashion which varied with temperature, external Ca2+ concentration, and liposome PE content. (ii) Addition of AdM was qualitatively equivalent to increasing temperature, Ca2+ concentration, or liposome PE content, and cooperative interactions among these parameters were observed. An increase in any one factor generally enhanced Ca2+ uptake; simultaneous increases in several factors inhibited uptake. (iii) Inhibition of Ca2+ uptake was correlated with efflux of Arsenazo III. (iv) Ca2+ uptake by PC/PE/CL liposomes is biphasic [Kester and Sokolove (1989) Biochim. Biophys. Acta 980, 127]. DM suppressed the PE-dependent slow phase and stimulated the PE-independent initial phase. Ca2+ uptake by PC/PE/CL liposomes in the presence of DM resembled uptake by PC/CL liposomes. These data confirm the ability of PE to enhance the slow, highly temperature-dependent component of CL-mediated Ca2+ translocation and suggest that this process is sensitive to lipid phase behavior.
Kester
M B
MB
University-Wide Toxicology Program, University of Maryland School of Medicine, Baltimore 21201.
Sokolove
P M
PM
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001430:Bacteriocins; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D008081:Liposomes; D008563:Membrane Lipids / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D010455:Peptides / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D013696:Temperature
D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D008081:Liposomes; D008563:Membrane Lipids; D010455:Peptides; D010714:Phosphatidylethanolamines; C040522:duramycin; D004317:Doxorubicin; D002118:Calcium