Biochim Biophys Acta. 1992 Jun 5;1126(1):41-8.
Inhibition of the accumulation of lipid droplets in
macrophage J774 by bafilomycin B1 and destruxin
Naganuma S, Kuzuya N, Sakai K, Hasumi K, Endo A.
Department of Applied Biological Science, Tokyo Noko
University, Japan.
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 microM, respectively, in macrophage J774. The
incorporation of [14C]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 125I-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 microM 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.
PMID: 1606174 |
