scholarly journals Cholesterol derivative of a new triantennary cluster galactoside directs low- and high-density lipoproteins to the parenchymal liver cell

1994 ◽  
Vol 302 (1) ◽  
pp. 283-289 ◽  
Author(s):  
E A L Biessen ◽  
H Vietsch ◽  
T J C Van Berkel
Keyword(s):  
Liver Cell ◽  
Parenchymal Cell ◽  
Density Lipoprotein ◽  
Hepatic Uptake ◽  
The Body ◽  
Liver Uptake ◽  
Terminal Galactose ◽  
Parenchymal Liver Cell ◽  
Parenchymal Liver ◽  
Branching Point

We have developed a new triantennary galactoside, in which the terminal galactose moieties are connected to the branching point of the cluster galactoside via a 20 A (2 nm) spacer [TG(20A)]. In vitro binding studies have demonstrated that introduction of a 20 A spacer resulted in avid and specific binding of the triantennary galactoside to the asialoglycoprotein receptor on the parenchymal liver cell. Derivatization of this galactoside with a cholesterol moiety afforded a compound [TG(20A)C] that lowered the serum cholesterol concentration when injected into rats. In the present study we have evaluated the direct effect of TG(20A)C on the in vivo fate of high-density lipoprotein (HDL) and low-density lipoprotein (LDL). A direct association of TG(20A)C with HDL and LDL was observed on mixing these components. Incorporation of TG(20A)C into 125I-HDL and 125I-LDL significantly accelerated the serum decay and concomitantly stimulated the hepatic uptake of these lipoproteins in rats. The liver uptake of TG(20A)C-loaded 125I-HDL or 125I-LDL could be inhibited by 81% and 82% respectively by preinjection of 150 mg of N-acetylgalactosamine, indicating that the enhanced liver uptake proceeded via galactose-specific receptors. More than 96% of the hepatic uptake of TG(20A)C-loaded 125I-HDL could be attributed to the parenchymal cell. Surprisingly, the parenchymal cell also accounted for 93% of the liver association of TG(20A)C-loaded 125I-LDL, suggesting that TG(20A)C stimulates the uptake and processing of both lipoproteins by the asialoglycoprotein receptor on the parenchymal liver cell. This contrasts with earlier data indicating that a triantennary cluster galactoside provided with a 4 A spacer between the terminal galactose moieties and the branching point of the dendrite stimulated hepatic uptake of LDL via the Kupffer cells. The parenchymal cell is the only liver cell type that is capable of irreversibly removing cholesterol from the body in the form of bile acids. The above results imply that administration of TG(20A)C not only facilitates the hepatic uptake of lipoprotein-derived cholesterol (esters) but also their elimination from the body. In addition, it might be possible to utilize TG(20A)C as a targeting device to selectively deliver large drug carriers and possibly genes to the parenchymal liver cell.

scholarly journals EVIDENCE FOR THE PARTICIPATION OF THE GOLGI APPARATUS IN THE INTRACELLULAR TRANSPORT OF NASCENT ALBUMIN IN THE LIVER CELL

1970 ◽  
Vol 47 (3) ◽  
pp. 555-567 ◽  
Author(s):  
Hans Glaumann ◽  
Jan L. E. Ericsson
Keyword(s):  
Endoplasmic Reticulum ◽  
Golgi Apparatus ◽  
Liver Cell ◽  
Intracellular Transport ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Parenchymal Liver Cell ◽  
Parenchymal Liver ◽  
Membrane Bound

A comparative biochemical and radioautographic in vivo study was performed to identify the site of synthesis and route of migration of albumin in the parenchymal liver cell after labeling with leucine-14C or leucine-3H via the portal vein. Free cytoplasmic ribosomes, membrane-bound ribosomes, rough- and smooth-surfaced microsomes, and Golgi membranes were isolated. The purity of the Golgi fraction was examined morphologically and biochemically. After administration of leucine-14C, labeled albumin was extracted, and the sequence of transport was followed from one fraction to the other. Approximately 2 min after the intravenous injection, bound ribosomes displayed a maximal rate of leucine-14C incorporation into albumin. 4 min later, a peak was reached for rough microsomes. Corresponding maximal activities for smooth microsomes were recorded at 15 min, and for the Golgi apparatus at ∼20 min. The relative amount of albumin, calculated on a membrane protein basis, was higher in the Golgi fraction than in the microsomes. By radioautography the silver grains were preferentially localized over the rough-surfaced endoplasmic reticulum at the 5 min interval. Apparent activity in the Golgi zone was noted 9 min after the injection; at 15 and 20 min, the majority of the grains were found in this location. Many of the grains associated with the Golgi apparatus were located over Golgi vacuoles containing 300–800 A electron-opaque bodies. It is concluded that albumin is synthesized on bound ribosomes, subsequently is transferred to the cavities of rough-surfaced endoplasmic reticulum, and then undergoes migration to the smooth-surfaced endoplasmic reticulum and the Golgi apparatus. In the latter organelle, albumin can be expected to be segregated together with very low density lipoprotein in vacuoles known to move toward the sinusoidal portion of the cell and release their content to the blood.

The Role of the Low-Density Lipoprotein Receptor-Related Protein (LRP) in the Plasma Clearance and Liver Uptake of Recombinant Single-chain Urokinase-type Plasminogen Activator in Rats

1997 ◽  
Vol 77 (04) ◽  
pp. 710-717 ◽  
Author(s):  
Marieke E van der Kaaden ◽  
Dingeman C Rijken ◽  
J Kar Kruijt ◽  
Theo J C van Berkel ◽  
Johan Kuiper
Keyword(s):  
Plasminogen Activator ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Single Chain ◽  
Liver Uptake ◽  
Type Plasminogen Activator ◽  
Parenchymal Liver ◽  
Urokinase Type Plasminogen Activator ◽  
Density Lipoprotein Receptor

SummaryUrokinase-type plasminogen activator (u-PA) is used as a thrombolytic agent in the treatment of acute myocardial infarction. In vitro, recombinant single-chain u-PA (rscu-PA) expressed in E.coli is recognized by the Low-Density Lipoprotein Receptor-related Protein (LRP) on rat parenchymal liver cells. In this study we investigated the role of LRP in the liver uptake and plasma clearance of rscu-PA in rats. A preinjection of the LRP inhibitor GST-RAP reduced the maximal liver uptake of 125I-rscu-PA at 5 min after injection from 50 to 30% of the injected dose and decreased the clearance of rscu-PA from 2.37 ml/min to 1.58 ml/min. Parenchymal, Kupffer and endothelial cells were responsible for 40, 50 and 10% of the liver uptake, respectively. The reduction in liver uptake of rscu-PA by the preinjection of GST-RAP was caused by a 91 % and 62% reduction in the uptake by parenchymal and Kupffer cells, respectively. In order to investigate the part of rscu-PA that accounted for the interaction with LRP, experiments were performed with a mutant of rscu-PA lacking residues 11-135 (= deltal25- rscu-PA). Deletion of residues 11-135 resulted in a 80% reduction in liver uptake and a 2.4 times slower clearance (0.97 ml/min). The parenchymal, Kupffer and endothelial cells were responsible for respectively 60, 33 and 7% of the liver uptake of 125I-deltal25-rscu-PA. Preinjection of GST-RAP completely reduced the liver uptake of delta 125-rscu-PA and reduced its clearance to 0.79 ml/min. Treatment of isolated Kupffer cells with PI-PLC reduced the binding of rscu-PA by 40%, suggesting the involvement of the urokinase-type Plasminogen Activator Receptor (u-PAR) in the recognition of rscu-PA. Our results demonstrate that in vivo LRP is responsible for more than 90% of the parenchymal liver cell mediated uptake of rscu-PA and for 60% of the Kupffer cell interaction. It is also suggested that u-PAR is involved in the Kupffer cell recognition of rscu-PA.

Disturbances of Bile Acid Metabolism in Parenchymal Liver Cell Disease

1977 ◽  
Vol 6 (1) ◽  
pp. 25-43
Author(s):  
Z.R. VLAHCEVIC ◽  
M.F. PRUGH ◽  
D.H. GREGORY ◽  
LEON SWELL
Keyword(s):  
Bile Acid ◽  
Liver Cell ◽  
Acid Metabolism ◽  
Bile Acid Metabolism ◽  
Cell Disease ◽  
Parenchymal Liver Cell ◽  
Parenchymal Liver

Quantitative evaluation of parenchymal liver cell volume and total hepatocyte number in cirrhotic patients

Hepatology ◽  
1991 ◽  
Vol 14 (3) ◽  
pp. 448-453 ◽  
Author(s):  
Hiroshi Imamura ◽  
Seiji Kawasaki ◽  
Junji Shiga ◽  
Yasutsugu Bandai ◽  
Kensho Sanjo ◽  
...  
Keyword(s):  
Cell Volume ◽  
Quantitative Evaluation ◽  
Liver Cell ◽  
Parenchymal Liver Cell ◽  
Parenchymal Liver ◽  
Cirrhotic Patients

Stimulation by Heparin of Parenchymal Liver Cell Proliferation in Normal Adult Rats

Nature ◽  
1961 ◽  
Vol 191 (4792) ◽  
pp. 1014-1015 ◽  
Author(s):  
M. ZIMMERMAN ◽  
EVEMARIE CELOZZI
Keyword(s):  
Cell Proliferation ◽  
Liver Cell ◽  
Normal Adult ◽  
Adult Rats ◽  
Parenchymal Liver Cell ◽  
Parenchymal Liver

scholarly journals Recognition of lactoferrin and aminopeptidase M-modified lactoferrin by the liver: involvement of proteoglycans and the remnant receptor

1996 ◽  
Vol 313 (1) ◽  
pp. 289-295 ◽  
Author(s):  
Gijsbertus J. ZIERE ◽  
J. Kar KRUIJT ◽  
Martin K. BIJSTERBOSCH ◽  
Theo J. C. van BERKEL
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Liver Cells ◽  
Recognition Site ◽  
Low Density ◽  
Liver Uptake ◽  
Aminopeptidase M ◽  
Parenchymal Liver ◽  
Parenchymal Cells ◽  
Initial Binding

1. Lactoferrin and aminopeptidase M-modified lactoferrin (APM-lactoferrin; which lacks its 14 N-terminal amino acids) inhibit the liver uptake of lipoprotein remnants. In the present study, the role of proteoglycans in the initial interaction of β-migrating very-low-density lipoprotein (β-VLDL), native and APM-lactoferrin with isolated rat parenchymal liver cells was investigated. Treatment of the cells with chondroitinase lowered the Kd of lactoferrin binding (from 10 to 2.4 μM), and the number of sites/cell (from 20×106 to 7×106), while heparinase treatment did not affect the binding. The binding characteristics of APM-lactoferrin and β-VLDL were not altered by treatment of the cells with chondroitinase or heparinase. It is concluded that proteoglycans are not involved in the initial binding of APM-lactoferrin and β-VLDL to parenchymal cells, while chondroitin sulphate proteoglycans are mainly responsible for the massive, low-affinity binding of native lactoferrin. 2. The binding of lactoferrin, APM-lactoferrin and β-VLDL to parenchymal liver cells was not influenced by the glutathione S-transferase-receptor-associated protein (GST-RAP) (97.2±4.0%, 95.5±3.7% and 98.5% of the control binding), while the binding of α2-macroglobulin was fully blocked at 10 μg/ml GST-RAP (1.8±0.5% of the control binding). Since GST-RAP blocks the binding of all the known ligands to the low-density lipoprotein (LDL)-receptor-related protein (LRP), it is concluded that LRP is not the initial primary recognition site for lactoferrin, APM-lactoferrin and β-VLDL on parenchymal liver cells. 3. We showed earlier that APM-lactoferrin, as compared with lactoferrin, is a more effective inhibitor of the liver uptake of lipoprotein remnants (49.4±4.0% versus 80.8±4.8% of the control at 500 μg/ml respectively). We found in the present study that β-VLDL is able to inhibit the binding of APM-lactoferrin to parenchymal liver cells significantly (74.9±3.3% of the control; P < 0.002), while the lactoferrin binding was unaffected. It is concluded that a still unidentified specific recognition site (the putative remnant receptor) is responsible for the initial binding of remnants to parenchymal cells and it is suggested that the partial cross-competition between APM-lactoferrin and β-VLDL may be of further help in the elucidation of the molecular nature of this recognition site.

Human parenchymal and non-parenchymal liver cell isolation, culture and characterization

2013 ◽  
Vol 7 (4) ◽  
pp. 951-958 ◽  
Author(s):  
Georg Damm ◽  
Elisa Pfeiffer ◽  
Britta Burkhardt ◽  
Jan Vermehren ◽  
Andreas K. Nüssler ◽  
...  
Keyword(s):  
Liver Cell ◽  
Cell Isolation ◽  
Parenchymal Liver Cell ◽  
Parenchymal Liver
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