title: Effect of simvastatin on the synthesis and secretion of lipoproteins in relation to the metabolism of cholesterol in cultured hepatocytes.
abstract: In primary culture of rat hepatocytes, simvastatin, a powerful HMGCoA reductase inhibitor, inhibited acetate incorporation into cellular and secreted cholesterol and cholesteryl-esters, without any significant effect on triacylglycerol synthesis and secretion. When applied to the culture for 24 h at 10(-7) M, a concentration shown to inhibit cholesterol synthesis by 61%, simvastatin increased apolipoprotein BH and BL synthesis and secretion and strongly decreased apolipoprotein AI synthesis and secretion whereas apolipoprotein AIV remained unaffected. The synthesis and secretion of apolipoprotein E was only slightly affected in contrast with other situations where cholesterol synthesis decreased. All of these modifications occurred at a post-transcriptional level, as the corresponding messenger RNAs of the apolipoproteins did not vary. These results suggest that either the drug itself or variations in cholesterol synthesis might be involved in apo B and apo AI synthesis and secretion.
authors.affiliation: Département de Biochimie, Faculté de Médecine Saint-Antoine, Université Pierre et Marie Curie, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Ribeiro
authors.forename: M
authors.initials: M
authors.lastname: Mangeney
authors.forename: C
authors.initials: C
authors.lastname: Loriette
authors.forename: G
authors.initials: G
authors.lastname: Thomas
authors.forename: D
authors.initials: D
authors.lastname: Pepin
authors.forename: B
authors.initials: B
authors.lastname: Janvier
authors.forename: J
authors.initials: J
authors.lastname: Chambaz
authors.forename: G
authors.initials: G
authors.lastname: Bereziat
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins / Q000096:biosynthesis* / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008715:Methionine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D019821:Simvastatin; D014280:Triglycerides / Q000378:metabolism
chemical_list: D002788:Cholesterol Esters; D005227:Fatty Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol; D008148:Lovastatin; D008715:Methionine; D019821:Simvastatin