title: Phenothiazines inhibit cholesteryl ester formation in J 774 monocyte-like cells.
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.
authors.affiliation: Laboratoire de Biochemie, CNRS UA 524, Faculté de Médecine Saint-Antoine, Paris, France.
authors.forename: N E
authors.initials: NE
authors.lastname: Houtia
authors.forename: J C
authors.initials: JC
authors.lastname: Mazière
authors.forename: C
authors.initials: C
authors.lastname: Mazière
authors.forename: M
authors.initials: M
authors.lastname: Auclair
authors.forename: J
authors.initials: J
authors.lastname: Gardette
authors.forename: J
authors.initials: J
authors.lastname: Polonovski
mesh_terms: D000818:Animals; D002460:Cell Line; D002746:Chlorpromazine / Q000494:pharmacology*; D002788:Cholesterol Esters / Q000096:biosynthesis / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000378:metabolism; D014268:Trifluoperazine / Q000494:pharmacology*; D014280:Triglycerides / Q000096:biosynthesis
chemical_list: D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D009829:Oleic Acids; D014280:Triglycerides; D014268:Trifluoperazine; D019301:Oleic Acid; D002785:Sterol O-Acyltransferase; D002746:Chlorpromazine