Regulation of HMG-CoA reductase, apoprotein-B and LDL receptor gene expression by the hypocholesterolemic drugs simvastatin and ciprofibrate in Hep G2, human and rat hepatocytes

摘要: The comparative effects of simvastatin (a competitive inhibitor HMG-CoA reductase) and ciprofibrate (another cholesterogenesis) on the incorporation [14C]acetate [3H]mevalonate into cholesterol reductase activity, apo-B synthesis, LDL receptor, their corresponding mRNAs, have been studied in human hepatoma cell line Hep G2 rat hepatocytes primary culture. Incubation with (0.01-1.5 microM) or (25-100 produced not only a marked inhibition cholesterogenesis from but also [3H]mevalonate, an intermediate downstream reaction. However, hepatocytes, cultured similar conditions, inhibited synthesis [14C]acetate, as expected. activity was greatly induced after incubation (up to 400% controls), ciprofibrate. Increased enzyme accompanied by higher content mRNA. Apo-B concentration medium cells 31% lower 31 h than controls. neither nor modified rate its mRNA level. Both LDL-receptor levels were raised at concentrations inhibiting synthesis. Our data show that, this line, triggers coordinate regulation expression genes coding for receptor apo-B. Ciprofibrate, though efficient cholesterogenesis, did induce same regulatory reactions. reason discrepancy is unknown.