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  • Title: Effects of simvastatin, a cholesterol synthesis inhibitor, on phosphatidylcholine synthesis in HepG2 cells.
    Author: Yanagita T, Yamamoto K, Ishida S, Sonda K, Morito F, Saku K, Sakai T.
    Journal: Clin Ther; 1994; 16(2):200-8. PubMed ID: 8062316.
    Abstract:
    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.
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