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 s ynthesis and phosphatidylcholine (PC) synthesis were studied in HepG2 cells. The cells were cultured with simvastatin at concentrations of 1 0(-7) and 10(-6) mol/L for 6 hours, and radioactive lipid precursors w ere added 1 hour before harvesting. Simvastatin inhibited cholesterol synthesis from [C-14]acetate in a dose-dependent manner. It also decre ased the incorporation of [C-14]choline into PC by 30%; this decrease was accompanied by a decrease in phosphocholine cytidylyltransferase a ctivity in cell homogenates. Simvastatin had no significant effects on the incorporation of [H-3]glycerol into phospholipids. These data ind icate that simvastatin has two different functions: inhibition of HMG- CoA reductase and depression of de novo synthesis of PC via the cytidi ne diphosphatecholine pathway, which, in turn, may result in a decreas e in plasma lipid levels.