2.P.11 Effects of atorvastatin on intracellular levels and stability of apolipoprotein B and HMG-CoA reductase in Hep G2 cells

The comparative study of effects of 5α-cholest-8(14)-en-15-on-3β-ol (I), (22E)-5α-ergosta-8(14),22-dien-15-on-3β-ol (II), (22S,23S)-22,23-oxido-5α-ergost-8(14)-en-15-on-3β-ol (III) and (22R,23R)-22,23-oxido-5α-ergost-8(14)-en-15-on-3β-ol (IV) on HMG-CoA reductase, CYP27A1 and CYP3A4 genes expression in Hep G2 cells was performed. In the contrast to 15-ketocholestane derivative (I), 15-ketoergostane derivatives (II - IV) decreased the HMG- CoA reductase mRNA level; (22R,23R)-22,23-oxido-5α-ergost-8(14)-en-15-on-3β-ol (IV) significantly increased CYP3A4 mRNA level (320% from control). Ketosterol (II) was found to be a more potent inhibitor of cholesterol biosynthesis in Hep G2 cells at a prolong incubation, compared with ketosterol (I). The side chain conformation of compounds (I) - (IV) was evaluated by computational modeling; the correlation between biological activity of these compounds and conformational flexibility of their side chains was found. The results obtained indicated that Δ8(14)-15-ketoergostane derivatives may be used as a sterol biosynthesis and metabolism regulators in liver cells.

Download Full-text

Effect of ketoconazole on cholesterol synthesis and on HMG-COA reductase and LDL-receptor activities in Hep G2 cells

Biochemical Pharmacology ◽

10.1016/0006-2952(87)90077-3 ◽

1987 ◽

Vol 36 (8) ◽

pp. 1245-1249 ◽

Cited By ~ 31

Author(s):

Herman Jan Kempen ◽

Kees Van Son ◽

Louis H. Cohen ◽

Marieke Griffioen ◽

Hans Verboom ◽

...

Keyword(s):

Cholesterol Synthesis ◽

Ldl Receptor ◽

Hep G2 ◽

Hep G2 Cells ◽

Hmg Coa Reductase ◽

G2 Cells ◽

Coa Reductase

Download Full-text

Effect of ethanol on cell growth and cholesterol metabolism in cultured Hep G2 cells

Biochemistry and Cell Biology ◽

10.1139/o03-066 ◽

2003 ◽

Vol 81 (6) ◽

pp. 379-386 ◽

Cited By ~ 6

Author(s):

Mónica P Polo ◽

Margarita G de Bravo ◽

María JT de Alaniz

Keyword(s):

Growth Rate ◽

Cell Growth ◽

Culture Medium ◽

Cholesterol Metabolism ◽

Reductase Activity ◽

Hep G2 ◽

Hep G2 Cells ◽

Hmg Coa Reductase ◽

G2 Cells ◽

Coa Reductase

The Hep G2 human hepatoma cell line has been recognized as an excellent in vitro human model system. For this reason, this line was used to study the effect of ethanol on HMG-CoA reductase activity concerning cell growth and cholesterol metabolism. Cells were incubated in ethanol-containing medium (0400 mmol/L) for up to 102 h. Ethanol caused an inhibition in the growth rate and in HMG-CoA reductase activity that could be reverted by the removal of ethanol from the culture medium, indicating no cellular damage. These changes cannot be ascribed to the regulatory effect of cholesterol levels, since its content was not modified either in the cells or in the medium. The addition of mevalonate to the culture medium could not revert the growth rate inhibition evoked by ethanol. Moreover, ethanol produced an increment in the cholesterol efflux in [3H]cholesterol-prelabeled cells. We conclude that the decrease in HMG-CoA reductase activity evoked by ethanol treatment on Hep G2 cells would not be the cause but the consequence of the impairment in cellular growth, since this impairment could not be reverted by the addition of mevalonate to the culture medium.Key words: ethanol, cholesterol, HMG-CoA reductase, hepatoma cells, lipid metabolism.

Download Full-text