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Publications (4)6.98 Total impact

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    ABSTRACT: 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, trifluoperazine or chlorpromazine decreased the degradation of acetylated low density lipoprotein by J 774 cells. When cell homogenates were preincubated in vitro with trifluoperazine or chlorpromazine, a marked inhibition of acylcoenzyme A: cholesterol-O-acyltransferase activity was observed. In cells incubated with acetylated low density lipoprotein loaded with radiolabeled cholesteryl-linoleate, trifluoperazine and chlorpromazine dramatically reduced the radioactivity recovered in cholesteryl esters. The radioactivity recovered in free cholesterol was also decreased, but to a lesser extent. These results suggest that phenothiazines could efficiently antagonize cholesteryl ester accumulation in macrophages by at least two different mechanisms: a reduction of modified LDL catabolism, and a direct inhibition of the enzyme acylcoenzyme A: cholesterol-O-acyltransferase.
    Journal of clinical chemistry and clinical biochemistry. Zeitschrift für klinische Chemie und klinische Biochemie 12/1988; 26(11):673-8.
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    ABSTRACT: Human foetal lung fibroblasts were pretreated for 24 h with the antithrombotic drug, suloctidil (1 to 10 mumol/l), which induced a dose-dependent increase in LDL binding, uptake and degradation. At 10 mumol/l suloctidil, the respective increases in these parameters were 40%, 80% and 50%. The same treatment also resulted in increases of 1.5 to 2-fold in the synthesis of sterols, fatty acids and triacylglycerols from sodium acetate. In contrast, the esterification of cholesterol with oleic acid was specifically decreased by 35% by 24 h pretreatment of fibroblasts with 10 mumol/l suloctidil. A similar decrease of cholesterol esterification was observed in cholesterol-laden fibroblasts. It is suggested that these effects of suloctidil on LDL processing and cholesterol metabolism are related to the amphiphilic characteristics of the drug and to its calcium-blocking properties.
    Journal of clinical chemistry and clinical biochemistry. Zeitschrift für klinische Chemie und klinische Biochemie 02/1988; 26(1):3-6.
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    ABSTRACT: The effect of three β-blockers: non-selective (propranolol), β1-selective (metoprolol), and with intrinsic sympathomimetic activity (pindolol), was investigated on 14C-oleic acid incorporation into cholesteryl esters in mouse peritoneal macrophages. Incorporation of 14C-oleic acid into cholesteryl esters was reduced about 10-fold by propranolol at 10−4 M while incorporation into triacylglycerols was only 30% decreased at the same concentration. Metoprolol and pindolol had no significant effect on 14C-oleic incorporation into cholesteryl esters or triacylglycerols. Finally, propranolol inhibited the acylcoenzyme A: cholesterol-O-acyltransferase activity, measured in vitro on macrophages homogenates, while the other studied β-blockers were ineffective. These results suggest that propranolol could antagonize cholesteryl ester accumulation by macrophages, one of the main processes involved in atherogenesis.
    Biochemical Pharmacology 04/1987; · 4.58 Impact Factor
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    ABSTRACT: The effect of dibutyryl-cyclic AMP (dbcAMP) and theophylline was investigated on oleic acid incorporation into cholesteryl esters and triacylglycerols in the mouse monocyte-macrophage cell line J 774. 24h pretreatment of macrophages with dbcAMP decreased cholesteryl ester formation in a dose-dependent manner (about 4 fold reduction for dbcAMP 10(-4)M + theophylline 10(-3)M), while oleic acid incorporation into triacylglycerols was markedly (2 to 3 fold) enhanced. The catabolism of acetylated LDL was only slightly affected (about 15-20% reduction with dbcAMP 5 X 10(-4)M + theophylline 10(-3)M). Acyl Coenzyme A: cholesterol-O-acyl-transferase activity, measured in vitro on cell homogenates, was reduced in dbcAMP-treated cells, whereas diacylglycerol acyltransferase activity was increased. These results suggest that cyclic AMP can modulate cholesteryl ester and triacylglycerol formation in macrophages, and that these metabolisms are inversely regulated. Agents which increase cyclic AMP intracellular level could be of interest for reducing cholesteryl ester accumulation in macrophages.
    Biochemical and Biophysical Research Communications 02/1987; 142(1):120-7. · 2.41 Impact Factor