Biomaterial Database

Interaction of Ca2+ with cardiolipin-containing liposomes and its inhibition by adriamycin. 1985

J M Brenza, and C E Neagle, and P M Sokolove

The interaction of cardiolipin-containing, unilamellar liposomes with Ca2+ was assessed by flow dialysis in the presence of 2-100 microM 45Ca2+, using vesicles formed from phosphatidylcholine (PC) and from PC and cardiolipin in mole ratios from 16:1 to 1:1. Control (PC only) vesicles bound no detectable Ca2+. In contrast, Ca2+ binding to cardiolipin-containing vesicles was substantial and dependent on vesicle concentration. Scatchard plots for the binding were concave upward. Resolution of the data, assuming the presence of two independent classes of binding sites, indicated a high-affinity site with apparent KD = 5.57 +/- 0.48 microM (S.D.) and a second site with KD in the millimolar range. Interaction of cardiolipin-containing liposomes with Ca2+ was insensitive to monovalent cations (Na+, K+, Rb+), but was inhibited by ruthenium red much greater than La3+ greater than Mn2+ greater than Mg2+. Progressive increases in the PC: cardiolipin ratio markedly increased the apparent KD for Ca2+ at the high-affinity site. Stoichiometry of Ca2+ binding at the site passed through a maximum at a PC: cardiolipin ratio of 4:1. The potent antineoplastic agent adriamycin also inhibited the interaction of Ca2+ with cardiolipin-containing liposomes in a dose-dependent manner; effects were detected at 10 microM antibiotic. Unlike PC, adriamycin altered the stoichiometry of the high-affinity interaction but not the apparent KD. Adriamycin effects increased with pH in the range of the pKA of its amino group. These results suggest that inhibition by adriamycin may result from a mechanism other than simple competition for the charged head group of cardiolipin.

UI	MeSH Term	Description	Entries
D008081	Liposomes	Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins.	Niosomes,Transferosomes,Ultradeformable Liposomes,Liposomes, Ultra-deformable,Liposome,Liposome, Ultra-deformable,Liposome, Ultradeformable,Liposomes, Ultra deformable,Liposomes, Ultradeformable,Niosome,Transferosome,Ultra-deformable Liposome,Ultra-deformable Liposomes,Ultradeformable Liposome
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002308	Cardiolipins	Acidic phospholipids composed of two molecules of phosphatidic acid covalently linked to a molecule of glycerol. They occur primarily in mitochondrial inner membranes and in bacterial plasma membranes. They are the main antigenic components of the Wassermann-type antigen that is used in nontreponemal SYPHILIS SERODIAGNOSIS.	Cardiolipin,Diphosphatidylglycerol,Diphosphatidylglycerols
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004317	Doxorubicin	Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.	Adriamycin,Adriablastin,Adriablastine,Adriblastin,Adriblastina,Adriblastine,Adrimedac,DOXO-cell,Doxolem,Doxorubicin Hexal,Doxorubicin Hydrochloride,Doxorubicin NC,Doxorubicina Ferrer Farm,Doxorubicina Funk,Doxorubicina Tedec,Doxorubicine Baxter,Doxotec,Farmiblastina,Myocet,Onkodox,Ribodoxo,Rubex,Urokit Doxo-cell,DOXO cell,Hydrochloride, Doxorubicin,Urokit Doxo cell
D006863	Hydrogen-Ion Concentration	The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH	pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining