Inhibition of the uptake of oxidized low-density lipoprotein in macrophage J774 by the antibiotic 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.
Hasumi
K
K
Department of Applied Biological Science, Tokyo Noko University, Fuchu-shi, Japan.
Shinohara
C
C
Naganuma
S
S
Endo
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002250:Carbon Radioisotopes; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D007769:Lactams; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages; D051379:Mice; D008985:Monensin / Q000494:pharmacology; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010084:Oxidation-Reduction; D011973:Receptors, LDL / Q000187:drug effects / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D002250:Carbon Radioisotopes; D007457:Iodine Radioisotopes; D007769:Lactams; D008077:Lipoproteins, LDL; D009829:Oleic Acids; D011973:Receptors, LDL; D019301:Oleic Acid; C074292:ikarugamycin; D002738:Chloroquine; D000255:Adenosine Triphosphate; D008985:Monensin