Stimulation of LDL receptor activity in Hep-G2 cells by a serum factor(s)

1988 ◽  
Vol 135 (2) ◽  
pp. 213-223 ◽  
Author(s):  
Jeff L. Ellsworth ◽  
Cynthia Brown ◽  
Allen D. Cooper
Keyword(s):  
Ldl Receptor ◽  
Receptor Activity ◽  
Serum Factor ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
G2 Cells ◽  
Stimulation Of

scholarly journals Porcine smooth muscle cell-conditioned medium stimulates LDL receptor activity in Hep G2 cells

1992 ◽  
Vol 103 (2) ◽  
pp. 541-549 ◽  
Author(s):  
C.D. Moorby ◽  
E. Gherardi ◽  
D. Riddell ◽  
D.E. Bowyer
Keyword(s):  
Smooth Muscle ◽  
Conditioned Medium ◽  
Mdck Cells ◽  
Ldl Receptor ◽  
Receptor Activity ◽  
Relative Molecular Mass ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Paracrine Factors ◽  
G2 Cells

Paracrine factors may modulate low density lipoprotein (LDL) receptor activity in hepatocytes. To study this the effect of conditioned medium prepared from a range of cell types on the binding and internalisation of 125I-LDL in Hep G2 cells was studied. Seven of the fourteen conditioned media tested, including those from P388D1, U937, porcine smooth muscle (Pc SMC) Swiss 3T3, STO, = 48 and MDCK cells, were found to increase the binding and internalisation of 125I-LDL at 37 degrees C by Hep G2 cells (P < 0.01). The largest increase in LDL receptor activity was produced by conditioned medium from Pc SMC cells and was, therefore, selected for further analysis. The Pc SMC-conditioned medium increased LDL receptor number in Hep G2 cells by three-fold but had no effect on LDL receptor activity in human skin fibroblasts. DNA synthesis and cholesterol synthesis by Hep G2 cells were inhibited by Pc SMC-conditioned medium. Preliminary characterisation of the Pc SMC-derived factor(s) suggests that it is a protein(s) of low relative molecular mass.

Transforming growth factor-β1 and interleukin-1β stimulate LDL receptor activity in Hep G2 cells

1992 ◽  
Vol 97 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Catriona D. Moorby ◽  
Ermanno Gherardi ◽  
Lynda Dovey ◽  
Cheryl Godliman ◽  
David E. Bowyer
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Ldl Receptor ◽  
Transforming Growth Factor Β1 ◽  
Receptor Activity ◽  
Interleukin 1Β ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
G2 Cells

scholarly journals Cellular free cholesterol in Hep G2 cells is only partially available for down-regulation of low-density-lipoprotein receptor activity

1987 ◽  
Vol 247 (3) ◽  
pp. 739-746 ◽  
Author(s):  
L M Havekes ◽  
E C M de Wit ◽  
H M G Princen
Keyword(s):  
Free Cholesterol ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Receptor Activity ◽  
Low Density ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Acat Activity ◽  
G2 Cells

We have previously shown that in Hep G2 cells and human hepatocytes, as compared with fibroblasts, the low-density lipoprotein (LDL) receptor activity is only weakly down-regulated after incubation of the cells with LDL, whereas incubation with high-density lipoproteins (HDL) of density 1.16-1.20 g/ml (heavy HDL) strongly increased the LDL-receptor activity. To elucidate this difference between hepatocytes and fibroblasts, we studied the cellular cholesterol homoeostasis in relation to the LDL-receptor activity in Hep G2 cells. (1) Interrupting the cholesteryl ester cycle by inhibiting acyl-CoA: cholesterol acyltransferase (ACAT) activity with compound 58-035 (Sandoz) resulted in an enhanced LDL-mediated down-regulation of the receptor activity. (2) The stimulation of the receptor activity by incubation of the cells with cholesterol acceptors such as heavy HDL was not affected by ACAT inhibition. (3) Incubation of the Hep G2 cells with LDL, heavy HDL or a combination of both grossly affected LDL-receptor activity, but did not significantly change the intracellular content of free cholesterol, suggesting that in Hep G2 cells the regulatory free cholesterol pool is small as compared with the total free cholesterol mass. (4) We used changes in ACAT activity as a sensitive (indirect) measure for changes in the regulatory free cholesterol pool. (5) Incubation of the cells with compactin (2 microM) without lipoproteins resulted in a 4-fold decrease in ACAT activity, indicating that endogenously synthesized cholesterol is directed to the ACAT-substrate pool. (6) Incubation of the cells with LDL or a combination of LDL and heavy HDL stimulated ACAT activity 3-5 fold, whereas incubation with heavy HDL alone decreased ACAT activity more than 20-fold. Our results suggest that in Hep G2 cells exogenously delivered (LDL)-cholesterol and endogenously synthesized cholesterol are primarily directed to the cholesteryl ester (ACAT-substrate) pool or, if present, to extracellular cholesterol acceptors (heavy HDL) rather than to the free cholesterol pool involved in LDL-receptor regulation.

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

Identification of a functional receptor differing from the LDL receptor that catabolizes chylomicron remnant in Hep G2 cells

1993 ◽  
Vol 104 (1-2) ◽  
pp. 105-115 ◽  
Author(s):  
K HAYASHI ◽  
K NAKASHIMA ◽  
M SAEKI ◽  
H KURUSHIMA ◽  
J KUROKAWA ◽  
...  
Keyword(s):  
Ldl Receptor ◽  
Chylomicron Remnant ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
G2 Cells ◽  
Functional Receptor

Comparison of the LDL-receptor binding of VLDL and LDL from apoE4 and apoE3 homozygotes

1999 ◽  
Vol 276 (3) ◽  
pp. E553-E557 ◽  
Author(s):  
Cyril D. S. Mamotte ◽  
Marian Sturm ◽  
Jock I. Foo ◽  
Frank M. van Bockxmeer ◽  
Roger R. Taylor
Keyword(s):  
Plasma Lipids ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Cultured Fibroblasts ◽  
Ldl Receptors ◽  
G2 Cells

Compared with apolipoprotein E3 (apoE3), apoE2 is less effective in mediating the binding of lipoproteins to the low-density lipoprotein (LDL) receptor. The influence of the E4 isoform, which is associated with adverse effects on plasma lipids and coronary heart disease, is less clear. We compared the ability of very low density lipoprotein (VLDL) and LDL from paired E4/4 and E3/3 subjects to compete against125I-labeled LDL for binding with the LDL receptor on cultured fibroblasts and Hep G2 cells. The concentrations of VLDL or LDL required to inhibit binding of125I-LDL by 50% (IC50, μg apoB/ml) were determined, and results were assessed in terms of an IC50 ratio, E4/4 IC50 relative to E3/3 IC50, to reduce the influence of interassay variability. In Hep G2 cells, E4/4 VLDL was more effective than E3/3 VLDL in competing for the LDL receptor, the IC50 ratio being lower than unity (0.73 ± 0.31, P < 0.05, two-tailed t-test). IC50 values themselves were marginally lower in E4/4 than E3/3 subjects (3.7 ± 1.3 vs. 6.1 ± 3.7, P < 0.08). However, there was no difference between E4/4 and E3/3 VLDL in competing for the LDL receptor on fibroblasts or between E4/4 and E3/3 LDL in competing for the LDL receptor on either cell type. These results suggest that inheritance of apoE4 is associated with an increased affinity of VLDL particles for LDL receptors on hepatocytes and may partly explain the influence of the E4 isoform on lipid metabolism.

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 Stimulation of the LDL receptor activity in the human hepatoma cell line Hep G2 by high-density serum fractions

1986 ◽  
Vol 875 (2) ◽  
pp. 236-246 ◽  
Author(s):  
Louis M. Havekes ◽  
Donald Schouten ◽  
Elly C.M. de Wit ◽  
Louis H. Cohen ◽  
Marieke Griffioen ◽  
...  
Keyword(s):  
Cell Line ◽  
Hepatoma Cell ◽  
Ldl Receptor ◽  
Receptor Activity ◽  
Hepatoma Cell Line ◽  
Human Hepatoma ◽  
Hep G2 ◽  
Human Hepatoma Cell ◽  
Serum Fractions ◽  
Stimulation Of

scholarly journals Evidence for sterol-independent regulation of low-density lipoprotein receptor activity in Hep-G2 cells

1991 ◽  
Vol 279 (1) ◽  
pp. 175-187 ◽  
Author(s):  
J L Ellsworth ◽  
C Chandrasekaran ◽  
A D Cooper
Keyword(s):  
Low Density Lipoprotein ◽  
Calf Serum ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Cholesteryl Esters ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Ldl Uptake ◽  
Stimulation Of

The relationship between the serum factor(s)-mediated induction of low-density lipoprotein (LDL) receptor activity and changes in cellular cholesterol metabolism was examined in the human hepatoma cell line Hep-G2. Relative to incubation with serum-free media [Eagle's minimal essential medium (MEM) control], short-term (less than 8 h) incubation with medium containing 15% of either calf serum (MEM + serum) or the d greater than 1.25 fraction of calf serum (MEM + d greater than 1.25) produced a time- and concentration-dependent increase in the uptake of 125I-LDL. Immunoblotting with anti-(LDL receptor) antibodies demonstrated that this was correlated with a 2-fold increase in the amount of the mature 136,000 Da LDL receptor protein in detergent-solubilized Hep-G2 cell membranes. Incubation with MEM + serum, but not MEM + d greater than 1.25, increased the efflux of radiolabelled cholesterol from Hep-G2 cells. However, the induction of 125I-LDL uptake by MEM + d greater than 1.25 (2.3-fold) and MEM + serum (2.2-fold) was virtually identical. Addition of the d less than 1.063 lipoproteins of calf serum to MEM + d greater than 1.25 at their original or three times their serum concentration decreased the induction of 125I-LDL uptake by MEM + d greater than 1.25 by only 20-30%. Together, these results suggest that the stimulation of 125I-LDL uptake was not due to the presence of high-density lipoprotein, the absence of LDL or the stimulation of cholesterol efflux. MEM + serum stimulated 125I-LDL uptake in cells cholesterol-loaded by incubation with rat very-low-density lipoprotein with beta electrophoretic mobility (beta-VLDL). Compared to incubation with the MEM control, either MEM + serum or MEM + d greater than 1.25 produced time-dependent increases in the activity of 3-hydroxy-3-methylglutaryl-CoA reductase which also occurred in cholesterol-loaded cells. However, cholesterol biosynthesis, whether measured from 3H2O, [14C]acetate or [3H]mevalonic acid, was not increased. Incubation with MEM + serum or MEM + d greater than 1.25 did not affect [3H]oleate incorporation into cellular cholesteryl esters, hydrolysis of intracellular [3H]cholesteryl esters or the cellular mass of unesterified or esterified cholesterol. Incubation with MEM + serum or MEM + d greater than 1.25 produced a transient increase in the level of LDL receptor mRNA, reaching a maximum of 5-10-fold by 2 h and decreasing to near baseline levels by 4 h. Actinomycin D blocked the serum-factor-mediated induction of LDL receptor mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)

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