Lipid metabolism in Hep G2 cultured cells treated with HMG-CoA reductase inhibitors

POLO M; BELLINI MJ.; BRAVO MG DE

San Carlos de Bariloche, Argentina

Congreso; XXXIX Anual Meeting of SAIB; 2003

SAIB

HMG-CoA reductase inhibitors like statins and monoterpenes diminish cellular cholesterol content. This fact increases the proteolysis of the sterol regulatory element binding protein (SREBP), which bind to sterol regulatory elements contained in promoters of genes involved in the synthesis of LDL receptors and key enzymes of cholesterol and fatty acid metabolism. We investigated the alterations produced by simvastatin (a statin) and geraniol (a natural monoterpene) on lipid metabolism in Hep G2 cells. Cells were treated with 1mM simvastatin (S), 10 mM geraniol (G) or 1mM simvastatin + 10 mM geraniol (SG)  for 24 h. Three hours prior to starvation, 14C-acetate (1mCi/ml) was added. Total lipids were extracted and 14C incorporation in non saponifiable lipids, fatty acids, neutral  and phospholipids were determined. All treatments incremented 14C incorporation in total lipids and in fatty acids. S and SG groups showed a greater 14C incorporation in all phopholipid fractions, G group did not show and increment in the incorporation in PC. All groups showed a diminished 14C incorporation in cholesterol, S group also in lanosterol and squalene, but G group increased its incorporation in squalene. These results demonstrated that all treatments augmented fatty acid synthesis and diminished cholesterol synthesis. Geraniol is likely to inhibit PC synthesis due to the accumulation of an intermediate metabolite as a consequence of an inhibition of the conversion of squelene into cholesterol.