Effects of simvastatin, a cholesterol synthesis inhibitor, on phosphatidylcholine synthesis in HepG2 cells.
The effects of the addition of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, simvastatin, to the medium on sterol synthesis and phosphatidylcholine (PC) synthesis were studied in HepG2 cells. The cells were cultured with simvastatin at concentrations of 10(-7) and 10(-6) mol/L for 6 hours, and radioactive lipid precursors were added 1 hour before harvesting. Simvastatin inhibited cholesterol synthesis from [14C]acetate in a dose-dependent manner. It also decreased the incorporation of [14C]choline into PC by 30%; this decrease was accompanied by a decrease in phosphocholine cytidylyltransferase activity in cell homogenates. Simvastatin had no significant effects on the incorporation of [3H]glycerol into phospholipids. These data indicate that simvastatin has two different functions: inhibition of HMG-CoA reductase and depression of de novo synthesis of PC via the cytidine diphosphate-choline pathway, which, in turn, may result in a decrease in plasma lipid levels.
Yanagita
T
T
Department of Applied Biological Sciences, Saga University, Japan.
Yamamoto
K
K
Ishida
S
S
Sonda
K
K
Morito
F
F
Saku
K
K
Sakai
T
T
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002784:Cholesterol / Q000096:biosynthesis; D002794:Choline / Q000378:metabolism; D002797:Choline Kinase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D019821:Simvastatin; D014407:Tumor Cells, Cultured
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010713:Phosphatidylcholines; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin; D002797:Choline Kinase; D002794:Choline