The effect of phenothiazines (trifluoperazine and chlorpromazine) on cholesteryl ester metabolism has been investigated in J 774 mouse monocyte-macrophages. The incorporation of oleic acid into cholesteryl ester and the activity of acylcoenzyme A: cholesterol-O-acyltransferase were strongly decreased in cells pretreated for 24 h with trifluoperazine or chlorpromazine. Furthermore, trifluoperazi...

Accumulation of lipid-laden foam cells of monocyte origin plays an important role in atherogenesis. Therefore, for determination of the mechanism of accelerated atherogenesis in Werner's syndrome, studies were carried out on the metabolism of acetylated low density lipoprotein (LDL) by monocyte-derived macrophages from patients with this syndrome. These macrophages showed abnormally high activi...

Lysosomal accumulation of unesterified (free) cholesterol, following the phagocytic incorporation of cholesteryl oleate lipid droplets, was quantitatively characterized in a murine J774 macrophage foam cell model. The induction of phagocytic incorporation by the macrophages, using an inverted culture technique, allowed the rapid delivery of large amounts of cholesteryl ester droplets to the lys...

Apolipoproteins of high density lipoprotein (HDL) and especially apolipoprotein (apo)AI and apoAII have been demonstrated as binding directly to the class B type I scavenger receptor (SR-BI), the HDL receptor that mediates selective cholesteryl ester uptake. However, the functional relevance of the binding capacity of each apolipoprotein is still unknown. The human adrenal cell line, NCI-H295R,...

Natural abundance Fourier transform 13C NMR spectra were obtained at 63.4 kG for human plasma high density lipoproteins (HDL) at several temperatures between 21°C and 36.5”C. At a given temperature, spectra of HDL, HDL2, and HDL3 are similar; linewidths for corresponding resonances are not distinguishable within experimental error. Improved resolution in HDL spectra at high field yields a numbe...

acyl-CoA and cholesterol. This enzyme plays key roles in both intestinal absorption of cholesterolX) and cholesteryl ester accumulation in macrophagederived foam cells, which are prominent in atherosclerotic plaques2). In the course of the search for microbial metabolites which inhibit cholesteryl ester formation in macrophages, helminthosporol (1)3), helminthosporal-derived acid (2)4) and helm...

To test the hypothesis that newly synthesized cholesteryl esters are required for hepatic lipoprotein assembly and secretion, isolated livers of African green monkeys were perfused with medium containing an ACAT inhibitor. Three ACAT inhibitors with different structural and chemical properties were used: CI-976 (Parke-Davis), CP-113818 (Pfizer), or PD-138142-15 (Parke-Davis). Each compound prod...

The human monocytic leukemia cell line, THP-1, shares many properties with human monocyte-derived macrophages and might be a useful model for studying foam cell formation in vitro. Therefore, we examined the ability of THP-1 cells to accumulate cholesteryl esters, the hallmark feature of foam cells, in response to culture with native low density lipoprotein (LDL), modified LDL, and platelets. T...

In vitro lipoprotein lipase enhances the cholesteryl ester transfer protein (CETP)-mediated transfer of cholesteryl esters from high density lipoproteins (HDL) to very low density lipoproteins as a result of lipolysis-induced alterations in lipoprotein lipids that lead to increased binding of CETP. To determine if there are similar changes during alimentary lipemia, we measured the transfer of ...