scholarly journals Glucagon, cyclic AMP and adrenaline stimulate the degradation of low-density lipoprotein by cultured rat hepatocytes

1989 ◽  
Vol 262 (2) ◽  
pp. 425-429 ◽  
Author(s):  
N F Brown ◽  
A M Salter ◽  
R Fears ◽  
D N Brindley
Keyword(s):  
Cyclic Amp ◽  
Actinomycin D ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Rat Hepatocytes ◽  
Low Density ◽  
Cultured Rat Hepatocytes

Rat hepatocytes were preincubated for 16 h with hormones or drugs and then for a further 8 h with 125I-human low-density lipoprotein (LDL). Glucagon (via cyclic AMP) and adrenaline (via cyclic AMP and alpha-effects) increased the binding of 125I-LDL to the LDL receptor, and the degradation of LDL to [125I]iodotyrosine. The effects on degradation were antagonized by dexamethasone, and the action of cyclic AMP on binding and degradation was inhibited by actinomycin D. The results are discussed in relation to the control of lipoprotein metabolism in diabetes.

scholarly journals Regulation of low-density-lipoprotein metabolism in the rat

1986 ◽  
Vol 234 (2) ◽  
pp. 493-496 ◽  
Author(s):  
S Bhattacharya ◽  
S Balasubramaniam ◽  
L A Simons
Keyword(s):  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Hormonal Control ◽  
Low Density ◽  
Experimental Conditions ◽  
Synthetic Rate ◽  
Catabolic Rate ◽  
Intermediate Density

The mechanism of regulation of plasma low-density-lipoprotein (LDL) metabolism in the rat was studied under a number of experimental conditions. LDL clearance and uptake in the liver was measured after intravenous pulse injection of [14C]sucrose-labelled LDL alone or in combination with reductively methylated [3H]sucrose-labelled LDL. Hyperthyroid rats showed a significant increase in fractional catabolic rate (FCR) and the proportion of LDL degraded in the liver, whereas the synthetic rate of LDL increased by 50%. Receptor-mediated clearance increased 2-fold. Hypothyroid rats showed a significant increase in LDL concentration. The FCR and proportion of LDL degraded in the liver were decreased significantly. Receptor-mediated clearance was also reduced. Cholesterol feeding increased chylomicron, very-low-density-and intermediate-density-lipoprotein cholesterol concentrations, but there was no change in the LDL concentration, FCR or the synthetic rate of LDL. Cholestyramine feeding did not induce changes in the kinetic parameters. These results indicate that, in the rat, the hepatic LDL-receptor pathway is under hormonal control, whereas cholesterol and cholestyramine feeding have no demonstrated effect on LDL metabolism.

scholarly journals Hypercholesterolemia Due to Lipoprotein X: Case Report and Thematic Review

2019 ◽  
Vol 12 ◽  
pp. 117955141987868 ◽  
Author(s):  
Laura Kattah ◽  
Andrés Gómez ◽  
Sebastián Gutiérrez ◽  
Kathalina Puerto ◽  
Eiman D Moreno-Pallares ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Low Density Lipoprotein ◽  
Cholesterol Acyltransferase ◽  
Ldl Receptor ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Definitive Treatment ◽  
Primary Biliary Cholangitis ◽  
Low Density ◽  
Hepatic Diseases

The liver is a key organ in lipid and lipoprotein metabolism, hence hepatic diseases often manifest as lipid disturbances. Cholestatic liver diseases are frequently associated with an important increase in total cholesterol at the expense of lipoprotein X (LpX), an abnormal lipoprotein isolated and characterized in the 1960s to 1970s in patients with obstructive jaundice. Lipoprotein X is rich in phospholipids, albumin, and free cholesterol, has a density similar to low-density lipoprotein (LDL), and a size similar to very low-density lipoprotein (VLDL), which has hampered its detection through routine laboratory tests. Unlike LDL, LpX has no apoB-100, so it is not removed from circulation via the LDL receptor, and it is not clear whether or not it can be atherogenic. Although LpX was initially described in patients with cholestasis, it has also been found in patients with genetic deficiency of lecithin-cholesterol acyltransferase (LCAT), in patients who receive lipid-rich parenteral nutrition and most recently in patients with graft versus host disease of the liver. In the presence of LpX, plasma total cholesterol can rise up to 1000 mg/dL, which may lead to the development of skin xanthomas and hyperviscosity syndrome. Treatment of LpX-dependent hypercholesterolemia with conventional hypolipidemic drugs is frequently ineffective, and definitive treatment relies on correction of the underlying cause of cholestasis. Here, we present the case of a patient with LpX-dependent hypercholesterolemia in the context of primary biliary cholangitis.

scholarly journals Lysophosphatidylcholine metabolism and lipoprotein secretion by cultured rat hepatocytes deficient in choline

1989 ◽  
Vol 260 (1) ◽  
pp. 207-214 ◽  
Author(s):  
B S Robinson ◽  
Z Yao ◽  
D J Baisted ◽  
D E Vance
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Rat Hepatocytes ◽  
Cellular Protein ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Very Low Density Lipoproteins ◽  
Phosphatidylcholine Biosynthesis ◽  
Cultured Rat Hepatocytes ◽  
Phosphatidylcholine Synthesis

The metabolism of lysophosphatidylcholine was studied in cultured rat hepatocytes deficient in choline and methionine. Even though the cells were defective in phosphatidylcholine biosynthesis, the albumin-stimulated release of lysophosphatidylcholine (1.9 nmol/h per mg of cellular protein) was similar to that in hepatocytes supplemented with choline. Albumin also stimulated (1.4-fold) the release of phosphatidylcholine from the deficient cells. The extra phosphatidylcholine and lysophosphatidylcholine in the medium were largely recovered in the albumin fraction (density greater than 1.18 g/ml), suggesting that albumin released these lipids from hepatocytes because of binding to this protein. The secretion of glycerophosphocholine was decreased by about 40% by the addition of albumin. When choline-deficient hepatocytes were supplemented with lysophosphatidylcholine, it was transported into the cells and mainly acylated to form phosphatidylcholine, which increased in mass by 30-35% in the first 4 h of incubation. Lysophosphatidylcholine was shown to be as effective as choline in restoring the secretion of very-low-density lipoproteins to normal amounts, as judged by the secretion of triacylglycerol, phosphatidylcholine and the apolipoproteins associated with very-low-density lipoproteins. Thus phosphatidylcholine synthesis via reacylation of lysophosphatidylcholine, via the CDP-choline pathway or via methylation of phosphatidylethanolamine, will satisfy the requirements for secretion of very-low-density lipoprotein from hepatocytes.

Control of low density lipoprotein receptor gene expression in steroidogenic cells

1989 ◽  
Vol 67 (8) ◽  
pp. 968-973 ◽  
Author(s):  
Koichiro Takagi ◽  
Jerome F. Strauss III
Keyword(s):  
Gene Expression ◽  
Cyclic Amp ◽  
Granulosa Cells ◽  
Receptor Gene ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Steroidogenic Cells ◽  
Receptor Gene Expression

Low density lipoprotein (LDL)-carried cholesterol is a primary substrate for steroid hormone synthesis by luteinized human granulosa cells. Chorionic gonadotropin and 8-bromo-cAMP both increase LDL receptor levels in granulosa cells by stimulating accumulation of the receptor mRNA. LDL and 25-hydroxycholesterol reduce LDL receptor expression, but this suppressive effect is partially overcome by 8-bromo-cAMP. Using fusion gene constructs containing the LDL receptor gene promoter transfected into JEG-3 cells, a cyclic AMP responsive enhancer could not be identified in the LDL receptor gene upstream promoter in transfection studies. We suggest that the LDL receptor gene in human steroidogenic cells is under negative control by a sterol effector, but that a cyclic AMP triggered process overcomes, to some extent, the sterol-mediated suppression. The detailed mechanisms by which sterol and cyclic AMP modulate LDL receptor gene expression remain to be elucidated.Key words: low density lipoproteins, low density lipoprotein receptors, cholesterol, steroidogenesis, gonadotropins.

scholarly journals Low-Density Lipoprotein Receptor-Related Proteins in Skeletal Development and Disease

2017 ◽  
Vol 97 (3) ◽  
pp. 1211-1228 ◽  
Author(s):  
Tao Yang ◽  
Bart O. Williams
Keyword(s):  
Skeletal Development ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Protein Family ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor

The identification of the low-density lipoprotein receptor (LDLR) provided a foundation for subsequent studies in lipoprotein metabolism, receptor-mediated endocytosis, and many other fundamental biological functions. The importance of the LDLR led to numerous studies that identified homologous molecules and ultimately resulted in the description of the LDL-receptor superfamily, a group of proteins that contain domains also found in the LDLR. Subsequent studies have revealed that members of the LDLR-related protein family play roles in regulating many aspects of signal transduction. This review is focused on the roles of selected members of this protein family in skeletal development and disease. We present background on the identification of this subgroup of receptors, discuss the phenotypes associated with alterations in their function in human patients and mouse models, and describe the current efforts to therapeutically target these proteins to treat human skeletal disease.

scholarly journals Calcium-antagonists inhibit secretion of very-low-density lipoprotein from cultured rat hepatocytes

1987 ◽  
Vol 247 (2) ◽  
pp. 433-439 ◽  
Author(s):  
J O Nossen ◽  
A C Rustan ◽  
C A Drevon
Keyword(s):  
Calcium Antagonists ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Rat Hepatocytes ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Triacylglycerol Synthesis ◽  
Cultured Rat Hepatocytes

The effects of different calcium-antagonists on secretion of very-low-density lipoprotein (VLDL) from cultured rat hepatocytes were examined. Verapamil (an inhibitor of voltage-dependent calcium channels) and EGTA (a calcium chelator) decreased VLDL-triacylglycerol secretion in a concentration-dependent manner, with maximum inhibition (about 90%) at 0.2 mM-verapamil and 5 mM-EGTA. Inorganic calcium-antagonists such as lanthanum, nickel, cobalt and manganese decreased secretion of VLDL-triacylglycerol by 55-95%, whereas the calcium-agonist barium did not affect secretion. Inhibition of VLDL-triacylglycerol secretion appeared within 30 min, without inhibition of triacylglycerol synthesis. Pulse-chase experiments revealed that verapamil and cobalt inhibited the secretory pathway itself. Cobalt showed a concentration-dependent inhibition of VLDL-triacylglycerol secretion, with maximal effect at 8 mM. Although inhibition by cobalt was not completely reversible, Trypan Blue exclusion and lactate dehydrogenase leakage indicated that the hepatocytes were not injured by cobalt or any of the other calcium-antagonists tested. Inhibition of protein synthesis by cycloheximide did not affect triacylglycerol secretion (up to 2 h), and the observed effects were therefore probably not due to impaired production of apolipoproteins. Taken together, these results suggest that calcium is important for secretion of VLDL particles.

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