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

Eur J Biochem. 1992 Apr 15;205(2):841-6. doi: 10.1111/j.1432-1033.1992.tb16848.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Biological Transport / drug effects
  • Carbon Radioisotopes
  • Cell Line
  • Chloroquine / pharmacology
  • Humans
  • Iodine Radioisotopes
  • Kinetics
  • Lactams*
  • Lipoproteins, LDL / metabolism*
  • Macrophages
  • Mice
  • Monensin / pharmacology
  • Oleic Acid
  • Oleic Acids / metabolism
  • Oxidation-Reduction
  • Receptors, LDL / drug effects
  • Receptors, LDL / metabolism*


  • Anti-Bacterial Agents
  • Carbon Radioisotopes
  • Iodine Radioisotopes
  • Lactams
  • Lipoproteins, LDL
  • Oleic Acids
  • Receptors, LDL
  • Oleic Acid
  • ikarugamycin
  • Chloroquine
  • Adenosine Triphosphate
  • Monensin