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

2003 ◽  
Vol 81 (6) ◽  
pp. 379-386 ◽  
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 (0–400 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.

HMG CoA Reductase and LDL Receptor Genes Are Regulated Differently by 15-Ketosterols in Hep G2 Cells

1999 ◽  
Vol 259 (3) ◽  
pp. 688-694 ◽  
Author(s):  
Anastassia F. Kisseleva ◽  
Ludmila E. Goryunova ◽  
Richard Planells ◽  
Huguette Lafont ◽  
Christian Alquier
Keyword(s):  
Ldl Receptor ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Hmg Coa Reductase ◽  
G2 Cells ◽  
Coa Reductase

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

1997 ◽  
Vol 134 (1-2) ◽  
pp. 119
Author(s):  
K. Adeli ◽  
T. Romain ◽  
A. Mohammadi ◽  
R.S. Newton ◽  
R. Cheung ◽  
...  
Keyword(s):  
Apolipoprotein B ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Hmg Coa Reductase ◽  
G2 Cells ◽  
Coa Reductase

scholarly journals Regulation of cholesterol biosynthesis and metabolismin Hep G2 cells by δ8(14)-15-ketoergostane derivatives

2010 ◽  
Vol 56 (5) ◽  
pp. 576-586
Author(s):  
A.R. Mehtiev ◽  
V.I. Fedchenko ◽  
Ya.V. Tkachev ◽  
V.P. Timofeev ◽  
A.Yu. Misharin
Keyword(s):  
Cholesterol Biosynthesis ◽  
Mrna Level ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Hmg Coa Reductase ◽  
Side Chain Conformation ◽  
Genes Expression ◽  
G2 Cells ◽  
Coa Reductase ◽  
The Comparative Study

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.

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

1987 ◽  
Vol 36 (8) ◽  
pp. 1245-1249 ◽  
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

Hep-G2 cells and primary rat hepatocytes differ in their response to inhibitors of HMG-CoA reductase

1990 ◽  
Vol 170 (2) ◽  
pp. 726-734 ◽  
Author(s):  
Mary Kay Shaw ◽  
Roger S. Newton ◽  
Drago R. Sliskovic ◽  
Bruce D. Roth ◽  
Erika Ferguson ◽  
...  
Keyword(s):  
Rat Hepatocytes ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Hmg Coa Reductase ◽  
Primary Rat Hepatocytes ◽  
G2 Cells ◽  
Coa Reductase

Effect of geraniol on fatty-acid and mevalonate metabolism in the human hepatoma cell line Hep G2

2006 ◽  
Vol 84 (1) ◽  
pp. 102-111 ◽  
Author(s):  
Monica P Polo ◽  
Margarita G de Bravo
Keyword(s):  
Fatty Acid ◽  
Cell Line ◽  
Reductase Activity ◽  
Hepatoma Cell ◽  
Cellular Growth ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Hep G2 ◽  
Hmg Coa Reductase ◽  
Coa Reductase

Monoterpenes have multiple pharmacological effects on the metabolism of mevalonate. Geraniol, a dietary monoterpene, has in vitro and in vivo anti-tumor activity against several cell lines. We have studied the effects of geraniol on growth, fatty-acid metabolism, and mevalonate metabolism in the human hepatocarcinoma cell line Hep G2. Up to 100 µmol geraniol/L inhibited the growth rate and 3-hydroxymethylglutaryl coenzyme A reductase (HMG-CoA) reductase activity of these cells. At the same concentrations, it increased the incorporation of cholesterol from the medium in a dose-dependent manner. Geraniol-treated cells incorporated less 14C-acetate into nonsaponifiable lipids, inhibiting its incorporation into cholesterol but not into squalene and lanosterol. This is indicative of an inhibition in cholesterol synthesis at a step between lanosterol and cholesterol, a fact confirmed when cells were incubated with 3H-mevalonate. The incorporation of 3H-mevalonate into protein was also inhibited, whereas its incorporation into fatty acid increased. An inhibition of Δ5 desaturase activity was demonstrated by the inhibition of the conversion of 14C-dihomo-γ-linolenic acid into arachidonic acid. Geraniol has multiple effects on mevalonate and lipid metabolism in Hep G2 cells, affecting cell proliferation. Although mevalonate depletion is not responsible for cellular growth, it affects cholesterogenesis, protein prenylation, and fatty-acid metabolism.Key words: geraniol, Hep G2, HMG-CoA reductase, mevalonate, fatty acids.

scholarly journals Inhibition of HMG-CoA Reductase Activity from Active Compounds of Ginger (Zingiber officinale): In-Silico Study

2021 ◽  
Vol 1 (1) ◽  
pp. 32-38
Author(s):  
Rosario Trijuliamos Manalu ◽  
Imelia Omega Meheda ◽  
Cintya Octaviani
Keyword(s):  
In Silico ◽  
Cholesterol Metabolism ◽  
Raw Materials ◽  
Reductase Activity ◽  
Zingiber Officinale ◽  
Active Compounds ◽  
Hmg Coa Reductase ◽  
Conducting Research ◽  
Main Components ◽  
Coa Reductase

ABSTRAK   Koleterol merupakan salah satu dari lemak tubuh dalam asam lemak bebas dan ester, yang termasuk komponen utama selaput sel otak dan saraf. Namun, tidak jarang kolesterol menjadi penyebab penyakit terutama penyakit jantung yang terus meningkat setiap tahunnya di Indonesia. Sehingga perlu strategi pengobatan yang efektif dan aman dengan melakukan penelitian tanaman Indonesia sebagai upaya kemandirian bahan baku obat. Tujuan dari penelitian ini adalah untuk menentukan aktivitas penghambatan dari senyawa aktif tanaman Jahe pada HMG-KoA reduktase secara in-silico melalui penambatan molekul. Senyawa aktif yang digunakan dalam penelitian ini curcumin, capsaisin, gingerol, paradol, shogaol dilakukan docking molekuler menggunakan software PLANTS dengan tujuan untuk mengetahui score docking dan interaksi kelima senyawa terhadap enzim HMG-KoA reduktase yang berperan terhadap metabolism lemak/kolesterol. Senyawa pembanding yang digunakan adalah simvastatin dan atorvastatin yang merupakan obat lini pertama untuk pengobatan displipidemia. Hasil score docking menunjukkan bahwa kelima senyawa aktif yang digunakan sebagai ligan, menunjukkan score docking yang lebih rendah dibandingkan dengan ligan pembanding, sehingga kelima senyawa aktif ini mampu untuk menghambat biosintesis kolesterol atau kandidat obat baru pengganti simvastatin dan atorvastatin serta berpotensi sebagai dyslipidemia.   ABSTRACT Cholesterol is one of the body's fats in free fatty acids and esters, which are the main components of brain and nerve cell membranes. However, it is not uncommon for cholesterol to be the cause of disease, especially heart disease, which continues to increase every year in Indonesia. So it needs an effective and safe treatment strategy by conducting research on Indonesian plants as an effort to be independent of medicinal raw materials. The aim of this study was to determine the inhibitory activity of the active compound of Ginger plant on HMG-CoA reductase in-silico through molecular anchoring. The active compounds used in this study were curcumin, capsaicin, gingerol, paradol, shogaol. Molecular docking was carried out using PLANTS software with the aim of knowing the docking score and the interaction of the five compounds with the HMG-CoA reductase enzyme that plays a role in fat/cholesterol metabolism. Comparative compounds used are simvastatin and atorvastatin which are first-line drugs for the treatment of dysplipidemia.  

Enhanced erythropoietin secretion in hepatoblastoma cells in response to hypoxia

1989 ◽  
Vol 257 (4) ◽  
pp. C743-C749 ◽  
Author(s):  
M. Ueno ◽  
I. Seferynska ◽  
B. Beckman ◽  
J. Brookins ◽  
J. Nakashima ◽  
...  
Keyword(s):  
Mouse Liver ◽  
Culture Medium ◽  
Culture Media ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Cobaltous Chloride ◽  
Fetal Mouse ◽  
Fetal Mouse Liver ◽  
G2 Cells ◽  
Hepatoblastoma Cell Line

Erythropoietin (Ep) levels in spent culture media of a Hep G2 human hepatoblastoma cell line were measured by radioimmunoassay (RIA), fetal mouse liver erythroid colony formation (FMLC), and the exhypoxic polycythemic mouse assay (EHPCMA). The Hep G2 cells at high density produced approximately 700 mU/ml Ep when measured with the RIA. On the other hand, the Ep levels when assayed in EHPCMA and FMLC were 50 and 2,600 mU/ml, respectively. The bioactivity in FMLC was completely neutralized by an antibody to purified human recombinant Ep, indicating that the erythropoietic activity in the Hep G2 spent culture medium was immunologically equivalent to Ep. Ep levels in the medium from low-density Hep G2 cells in 5% O2 and 1% O2 were 2.5- and 4-fold greater, respectively, than that of 20% O2. In contrast, hyperoxia (40% O2) significantly inhibited Ep production. A significant increase in Ep secretion was also observed when the cells were incubated with cobaltous chloride (2 X 10(-6) -2.5 X 10(-4) M). Tunicamycin (0.5 micrograms/ml), which inhibits N-linked glycosylation, significantly reduced the enhancement of Ep secretion induced by hypoxia (1% O2) without affecting cell growth. Forskolin and cholera toxin, each of which increased the levels of cyclic AMP in the Hep G2 cells by 40-fold, produced a significant (P less than 0.05) further increase in Ep secretion in the presence of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effect of 25-hydroxycholesterol and bile acids on the regulation of cholesterol metabolism in Hep G2 cells

1989 ◽  
Vol 264 (1) ◽  
pp. 241-247 ◽  
Author(s):  
T L Carlson ◽  
B A Kottke
Keyword(s):  
Acetic Acid ◽  
Bile Acids ◽  
Cholesterol Synthesis ◽  
Cholesterol Metabolism ◽  
Mrna Levels ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Control Value ◽  
Apo E ◽  
G2 Cells

The effect of 25-hydroxycholesterol (25-OH-cholesterol) and chenodeoxycholic (CDC) acid on apoprotein secretion, low-density lipoprotein receptor activity, and [3H]triacylglycerol secretion in Hep G2 cells was studied. Both 25-OH-cholesterol and CDC acid increased the secretion of apolipoprotein (apo) E by Hep G2 cells. The secretion of apo A-I was slightly lowered (less than 10% disease). The maximal increase in apo E secretion was observed in culture medium containing 2 micrograms of 25-OH-cholesterol/ml or 10 micrograms of CDC acid/ml plus 10% fetal calf serum. Cholesterol, 7-OH-cholesterol and other bile acids were ineffective in inducing increases in apo E secretion. Another cholesterol synthesis inhibitor, mevinolin, was also ineffective in generating an increase in apoprotein secretion. The data indicated a specific interaction between 25-OH-cholesterol or CDC acid and apo E secretion in Hep G2 cells. Cholesterol synthesis, as measured by the incorporation of [14C]acetic acid into sterols, was repressed in Hep G2 cells in the presence of 25-OH-cholesterol (17% of control value). CDC acid, on the other hand, increased [14C]acetic acid incorporation (156% of control value). The number of LDL receptors in Hep G2 cells was decreased after incubation with 25-OH-cholesterol (62% of control value), but increased significantly after incubation with CDC acid (149% of control value). The secretion of [3H]triacylglycerol by Hep G2 cells incubated with 25-OH-cholesterol was greatly increased (248% of control value). On the contrary, CDC acid did not cause any increase in [3H]triacylglycerol secretion. The above results suggest that 25-OH-cholesterol and CDC acid have different effects on lipid metabolism in Hep G2 cells. The mRNA levels of apo E increased in cells preincubated with 25-OH-cholesterol and CDC acid, which suggested that the increase in apo E secretion is at least partly due to an increase in synthesis.

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