INHIBITION OF THE ACCUMULATION OF LIPID DROPLETS IN MACROPHAGE-J774 BY BAFILOMYCIN-B1 AND DESTRUXIN-E

Two microbial metabolites, bafilomycin B1 and destruxin E, have been found to inhibit significantly the oxidized low density lipoprotein (LDL)-induced accumulation of lipid droplets at 3 nM and 0.5-mu-M, respectively, in macrophage J774. The incorporation of [C-14]oleate into cholesteryl esters in the cells incubated with oxidized LDL was inhibited to the same extent by the two compounds. Both compounds had no effect on the cell surface binding at 4-degrees-C and the internalization of oxidized I-125-LDL as well as on the activity of acyl-CoA: cholesterol acyltransferase. However, when incubated with these compounds at 37-degrees-C, receptors for oxidized LDL were partially trapped within the cell. In accordance with receptor accumulation, ATP-dependent acidification of endosomes and lysosomes was significantly inhibited by 50 nM bafilomycin B1 and 1-mu-M destruxin E, respectively. From these results it was concluded that the inhibition of ATP-dependent acidification of endosomes and lysosomes by bafilomycin B1 and destruxin E resulted in the reduction of oxidized LDL-induced synthesis of cholesteryl ester and thereby caused a reduced accumulation of lipid droplets in macrophage J774.