Inhibition of the binding of oxidized low density lipoprotein to the macrophages by iturin C-related compounds.
Binding of modified lipoproteins including oxidized low density lipoprotein (oxidized LDL) to cell surface receptors is an initial step of conversion of monocyte-derived macrophages into lipid-laden foam cells, a key cellular component in the early lesions of atherosclerosis. We have searched for microbial metabolites that inhibit oxidized LDL-induced lipid accumulation in macrophages and isolated three compounds from a strain of Bacillus sp. as inhibitors of oxidized LDL binding. By chemical and spectroscopic analyses, these metabolites were shown to be related to the cyclic lipopeptide iturin C. Two of these compounds were novel metabolites having long chain beta-amino acid moieties of different length. These agents, at concentrations ranging from 5 to 20 microM, inhibited cell surface binding of oxidized 125I-LDL, resulting in reduced intracellular accumulation and degradation of the lipoprotein as well as in reduced cholesteryl ester formation from [14C]oleate in macrophages J774.
Park
J K
JK
Department of Applied Biological Science, Tokyo Noko University, Japan.
Hasumi
K
K
Endo
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001412:Bacillus subtilis; D002460:Cell Line; D002788:Cholesterol Esters / Q000096:biosynthesis; D008401:Gas Chromatography-Mass Spectrometry; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010443:Peptide Chain Termination, Translational; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism
D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D010456:Peptides, Cyclic; D011956:Receptors, Cell Surface; C033468:iturin C