Inhibition of the uptake of oxidized low‐density lipoprotein in macrophage J774 by the antibiotic ikarugamycin

Abstract

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 μM. 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 μM 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 μM ikarugamycin. The results demonstrated that ikarugamycin inhibited cholesteryl ester accumulation in macrophage J774 by specifically inhibiting the uptake of oxidized LDL. Copyright © 1992, Wiley Blackwell. All rights reserved