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.

scholarly journals The effects of monensin on secretion of very-low-density lipoprotein and metabolism of asialofetuin by cultured rat hepatocytes

1985 ◽  
Vol 227 (2) ◽  
pp. 529-536 ◽  
Author(s):  
A C Rustan ◽  
J ∅ Nossen ◽  
T Berg ◽  
C A Drevon
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Rat Hepatocytes ◽  
Low Density Lipoproteins ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Dependent Manner ◽  
Very Low Density Lipoproteins ◽  
Low Concentrations ◽  
Maximum Inhibition

Primary cultures of rat hepatocytes were used to study secretion of very-low-density lipoproteins and metabolism of asialofetuin. The ionophore monensin inhibited both secretion of very-low-density lipoproteins and binding and degradation of asialofetuin in a concentration-dependent manner. Secretion as well as receptor binding were markedly decreased after 15 min treatment with monensin. The inhibitory effect of the ionophore was fully reversible, and no effect on protein synthesis was observed at concentrations up to 50 microM. The secretion of apoproteins (B-small, B-large and E) and that of albumin were inhibited to the same extent as was triacylglycerol secretion. Secretion of very-low-density lipoproteins was more sensitive to low concentrations of monensin than was the metabolism of asialofetuin. Maximum inhibition of very-low-density-lipoprotein secretion was obtained at 5-10 microM-monensin, whereas 25 microM was required to obtain maximum inhibition of binding and degradation of asialofetuin. The number of surface receptors for asialofetuin decreased to about half when the cells were exposed to 25 microM-monensin. It is possible that monensin inhibits endo- and exo-cytosis via a similar mechanism, e.g. by disturbing proton gradients. Since secretion of very-low-density lipoproteins was more sensitive to low concentrations of monensin, it is likely that monensin independently inhibits endocytic and secretory functions in cultured hepatocytes.

scholarly journals Very low density lipoprotein synthesis and secretion by cultured rat hepatocytes.

1979 ◽  
Vol 254 (6) ◽  
pp. 2010-2016 ◽  
Author(s):  
R.A. Davis ◽  
S.C. Engelhorn ◽  
S.H. Pangburn ◽  
D.B. Weinstein ◽  
D. Steinberg
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Rat Hepatocytes ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Synthesis ◽  
Cultured Rat Hepatocytes

scholarly journals Very-Low-Density Lipoprotein Receptor Fragment Shed from HeLa Cells Inhibits Human Rhinovirus Infection

1998 ◽  
Vol 72 (12) ◽  
pp. 10246-10250 ◽  
Author(s):  
Thomas C. Marlovits ◽  
Christina Abrahamsberg ◽  
Dieter Blaas
Keyword(s):  
Hela Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Intercellular Adhesion Molecule ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Dependent Manner ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor

ABSTRACT The large family of human rhinoviruses, the main causative agents of the common cold, is divided into the major and the minor group based on receptor specificity. Major group viruses attach to intercellular adhesion molecule 1 (ICAM-1), a member of the immunoglobulin superfamily, whereas minor group viruses use low-density lipoprotein receptors (LDLR) for cell entry. During early attempts aimed at isolating the minor group receptor, we discovered that a protein with virus binding activity was released from HeLa cells upon incubation with buffer at 37°C (F. Hofer, B. Berger, M. Gruenberger, H. Machat, R. Dernick, U. Tessmer, E. Kuechler, and D. Blaas, J. Gen. Virol. 73:627–632, 1992). In light of the recent discovery of several new members of the LDLR family, we reinvestigated the nature of this protein and present evidence for its being derived from the human very-low density lipoprotein receptor (VLDLR). A soluble VLDLR fragment encompassing the eight complement type repeats and representing the N-terminal part of the receptor was then expressed in the baculovirus system; both the shed protein and the recombinant soluble VLDLR bind minor group viruses and inhibit viral infection of HeLa cells in a concentration-dependent manner.

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.

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