monensin and ikarugamycin

The antiprotozoal antibiotic ikarugamycin was found to significantly inhibit oxidized low-density lipoprotein(LDL)-induced accumulation of cholesteryl ester in macrophage J774 at a concentration over 1-4 microM. Cholesteryl ester synthesis from [14C]oleate in the macrophages was similarly inhibited by the antibiotic, while the synthesis of triacylglycerol and polar lipids was not affected. The internalization of oxidized [125I]LDL in macrophages was reduced to 50% by 2 microM ikarugamycin, while cell-surface binding of oxidized [125I]LDL, lysosomal hydrolysis of the internalized oxidized [125I]LDL and microsomal acyl-coenzyme A:cholesterol acyltransferase was not detectably inhibited by 5 microM ikarugamycin. The results demonstrated that ikarugamycin inhibited cholesteryl ester accumulation in macrophage J774 by specifically inhibiting the uptake of oxidized LDL.

Topics: Adenosine Triphosphate; Animals; Anti-Bacterial Agents; Biological Transport; Carbon Radioisotopes; Cell Line; Chloroquine; Humans; Iodine Radioisotopes; Kinetics; Lactams; Lipoproteins, LDL; Macrophages; Mice; Monensin; Oleic Acid; Oleic Acids; Oxidation-Reduction; Receptors, LDL