scholarly journals Cholesterol and bile acid synthesis in Hep G2 cells. Metabolic effects of 26- and 7 α-hydroxycholesterol

1989 ◽  
Vol 262 (3) ◽  
pp. 989-992 ◽  
Author(s):  
N B Javitt ◽  
K Budai
Keyword(s):  
Chenodeoxycholic Acid ◽  
Cholesterol Synthesis ◽  
Lithocholic Acid ◽  
Biological Effects ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Metabolic Effects ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
G2 Cells

1. Using a human hepatoma (Hep G2) cell line that continually synthesizes 3 beta-hydroxy-5-cholenoic acid, lithocholic acid, chenodeoxycholic acid and cholic acid we have determined the metabolism and biological effects of 26-hydroxycholesterol and 7 alpha-hydroxycholesterol. 2. Addition of 26-hydroxycholesterol to the medium (6 microM) downregulated cholesterol and chenodeoxycholic acid synthesis. 3. The predominant metabolite of 26-hydroxycholesterol was 3 beta-hydroxy-5-cholenoic acid. 4. Cholesterol synthesis was not affected by the addition of 7 alpha-hydroxycholesterol (6 and 12 microM). The predominant metabolite of 7 alpha-hydroxycholesterol was chenodeoxycholic acid. 5. In Hep G2 cells 7 alpha-hydroxylation of 26-hydroxycholesterol is not well expressed.

Hep G2 cells: a model for studies on regulation of human cholesterol 7alpha-hydroxylase at the molecular level

1996 ◽  
Vol 270 (3) ◽  
pp. G401-G410 ◽  
Author(s):  
W. M. Pandak ◽  
R. T. Stravitz ◽  
V. Lucas ◽  
D. M. Heuman ◽  
J. Y. Chiang
Keyword(s):  
Bile Acid ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Time Dependent ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Functional Studies ◽  
G2 Cells

The present study examines the feedback control governing human cholesterol 7alpha-hydroxylase mRNA expression in the human hepatoblastoma cell line, Hep G2. Glycochenodeoxycholate (GCDC) and glycodeoxycholate, hydrophobic bile salts, decreased cholesterol 7alpha-hydroxylase mRNA levels and bile acid synthesis in a concentration-dependent (76 +/- 8%, P<0.001, and 48 +/- 3%, P<0.01, respectively) and time-dependent manner. Cholesterol 7alpha-hydroxylase mRNA levels were repressed with a half-maximal inhibitory concentration of <12.5 microM by GCDC and a half-life of 30 min by 100 microM of the bile acid. The addition of actinomycin D (10 microgram/ml) alone or in combination with GCDC (100 microM) led to similar concentration-and time-dependent suppression of cholesterol 7alpha-hydroxylase mRNA. Glycocholate (100 microM), not internalized based on lack of uptake of a fluorescent cholate analogue, had no effect on cholesterol 7alpha-hydroxylase mRNA or total bile acid synthesis. In cultures transfected with a rat cholesterol 7alpha-hydroxylase promoter construct, reporter gene activity was decreased (31%, P<0.01) by GCDC (100 microM). Hep G2 cells maintain the intracellular machinery to express and rapidly regulate human cholesterol 7alpha-hydroxylase by hydrophobic bile acids. These data suggest that Hep G2 cells will support functional studies of the human cholesterol 7alpha-hydroxylase gene.

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.

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

scholarly journals Stevia: limiting cholesterol synthesis in Hep-G2 cells

2020 ◽  
pp. 110-119
Author(s):  
Amirul Nazhan Ilias ◽  
Hazilawati Hamzah ◽  
Intan Safinar Ismail ◽  
Mokrish Ajat
Keyword(s):  
Cholesterol Synthesis ◽  
De Novo ◽  
Stevia Rebaudiana ◽  
Dependent Manner ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
High Concentration ◽  
Immunofluorescent Microscopy ◽  
G2 Cells

As of today, no literature has been reported on the efficacy of stevia on lipid regulations conducted in vitro. Thus, the current study was focusing on the potential of Stevia rebaudiana bertoni as an anti-hypercholesterolemia substitute in limiting the de novo cholesterol synthesis in Hep-G2 cell line. The cytotoxicity and lipid internalization effects of stevia on Hep-G2 cells were assessed quantitatively and qualitatively in this study. As evaluated by MTT assay, commercialized stevia (0.5-20.0 mg/ml) and stevioside (1.0-10 µM) inhibited Hep-G2 cells viability in a dose-dependent manner for 24 hours. IC50 was detected at 8.68 mg/ml (commercialized stevia) and 10.91 µM (stevioside). From the assay, suitable concentrations were chosen to study the effect of stevia on cholesterol internalization in Hep-G2 cells supplemented with exogenous lipids. Cholesterol quantification assay revealed that high concentration commercialized stevia and stevioside promoted significant cholesterol internalized in Hep-G2 cells as compared to simvastatin. Finally, immunofluorescent microscopy assessment was done to qualitatively observe the formation of lipid droplets and low-density lipoprotein receptor in relation to total cholesterol extracted. The microphotographs of immunofluorescent microscopy were in parallel to results obtained from the cholesterol quantification assay which further revealed the effect of stevia as a potential anti-hypercholesterolemia agent.

Effect of simvastatin (MK-733) on the regulation of cholesterol synthesis in Hep G2 cells

1990 ◽  
Vol 40 (4) ◽  
pp. 843-850 ◽  
Author(s):  
Nagata Yasufumi ◽  
Hidaka Yusuke ◽  
Ishida Fumiaki ◽  
Kamei Toshio
Keyword(s):  
Cholesterol Synthesis ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
G2 Cells

scholarly journals Cerebrotendinous Xanthomatosis: diversity of presentation and refining treatment with chenodeoxycholic acid

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Mahjabin Islam ◽  
Nigel Hoggard ◽  
Marios Hadjivassiliou
Keyword(s):  
Chenodeoxycholic Acid ◽  
Clinical Characteristics ◽  
Spastic Paraparesis ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Cerebrotendinous Xanthomatosis ◽  
Juvenile Onset ◽  
Progressive Ataxia ◽  
Classical Triad ◽  
High Index Of Suspicion

Abstract Background Cerebrotendinous xanthomatosis (CTX) is a rare but treatable neurometabolic disorder of lipid storage and bile acid synthesis. Whilst CTX is said to present with the classic triad of juvenile onset cataracts, tendon xanthomata and progressive ataxia, the diversity of presentation can be such that the diagnosis may be substantially delayed resulting in permanent neurological disability. Methods A retrospective review of the clinical characteristics and imaging findings of 4 patients with CTX presenting to the Sheffield Ataxia Centre over a period of 25 years. Results Although CTX-related symptoms were present from childhood, the median age at diagnosis was 39 years. Only 1 of the 4 cases had tendon xanthomata, only 2 cases had juvenile onset cataracts and 3 had progressive ataxia with one patient presenting with spastic paraparesis. Serum cholestanol was elevated in all 4 patients, proving to be a reliable diagnostic tool. In addition, cholestanol was raised in the CSF of 2 patients who underwent lumbar puncture. Despite treatment with chenodeoxycholic acid (CDCA) and normalization of serum cholestanol, CSF cholestanol remained high in one patient, necessitating increase in the dose of CDCA. Further adjustments to the dose of CDCA in the patient with raised CSF cholestanol resulted in slowing of progression. Two of the patients who have had the disease for the longest continued to progress, one subsequently dying from pneumonia. Conclusion A high index of suspicion for CTX, even in the absence of the classical triad is essential in reaching such diagnosis. The earlier the diagnosis and treatment, the better the outcome.

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