The Experts below are selected from a list of 6840 Experts worldwide ranked by ideXlab platform
Richard J. Stockert - One of the best experts on this subject based on the ideXlab platform.
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Adaptor heat shock protein complex formation regulates trafficking of the Asialoglycoprotein receptor
American journal of physiology. Gastrointestinal and liver physiology, 2005Co-Authors: Tianmin Huang, Allan W. Wolkoff, Richard J. StockertAbstract:In the Asialoglycoprotein receptor (ASGPR) endocytic pathway, internalized receptors pass through early, recycling, and sorting endosomal compartments before returning to the cell surface. Sorting ...
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Regulation of the insulin and Asialoglycoprotein receptors via cGMP-dependent protein kinase.
American journal of physiology. Cell physiology, 2000Co-Authors: Luis A. De La Vega, Richard J. StockertAbstract:Biotin regulation of Asialoglycoprotein receptor expression and insulin receptor activity has been established in two human hepatoblastoma cell lines, Hep G2 and HuH-7. Second messenger cGMP mimics...
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Cytoplasmic protein mRNA interaction mediates cGMP-modulated translational control of the Asialoglycoprotein receptor.
The Journal of biological chemistry, 1997Co-Authors: Richard J. Stockert, Qing RenAbstract:Abstract Expression of the Asialoglycoprotein receptor by the human hepatocellular carcinoma cell line HuH-7 in response to intracellular cGMP concentrations was previously shown to be regulated at the translational level. In a cell-free system, initiation of Asialoglycoprotein receptor mRNA translation was dependent on the presence of the 7-methylguanylate cap site and was independent of 8-bromo-cGMP levels in which the cells were grown prior to RNA isolation. Stable transfection of COS-7 cells with deletion constructs of the Asialoglycoprotein receptor H2b subunit localized the cGMP-responsive cis-acting element to the mRNA 5′-untranslated region (UTR). Addition of biotin (an activator of guanylate cyclase) induced the expression of β-galactosidase present as a chimeric plasmid containing the H2b 187-nucleotide 5′-UTR. An RNA gel retardation assay identified a 37-nucleotide cognate sequence within this 187-nucleotide region. Titration of the 5′-UTR with a cytosolic fraction isolated from HuH-7 grown in the presence or absence of 8-bromo-cGMP or biotin provided direct evidence for an RNA-binding protein responsive to intracellular levels of cGMP. Based on these findings, it seems reasonable to propose that reduction of intracellular levels of cGMP by biotin deprivation results in a negative trans-acting factor associating with the 5′-UTR of Asialoglycoprotein receptor mRNAs, thereby inhibiting translation.
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Effects of cytokines on synthesis and function of the hepatic Asialoglycoprotein receptor.
Journal of cellular physiology, 1994Co-Authors: Ulrich Treichel, Elisabeth Paietta, Thomas Poralla, Karl Hermann Meyer Zum Büschenfelde, Richard J. StockertAbstract:In this study we have investigated whether cytokines, critical mediators of the immune response, might have a direct effect on the expression and/or function of the human hepatic Asialoglycoprotein receptor (ASGPR). Binding and uptake of Asialoglycoproteins by the human hepatoma cell line, HepG2, and by freshly isolated rat hepatocytes were inhibited by 50% after 3-6 hours and completely abolished following a 24 hour exposure to tumor necrosis factor (TNF) alpha, interferon (INF) alpha or gamma, or interleukin-2 (IL-2). The loss of ASGPR binding activity mediated by IL-2 was reversible up to 4 hours of exposure and accompanied by the selective phosphorylation of the cell-surface receptor. Steady-state levels of total cellular ASGPR protein remained unchanged over the first 6 hours of IL-2 incubation but declined in a dose dependent manner thereafter. This down regulation of ASGPR expression was due to reduced synthesis as a result of reduced receptor transcript levels. No loss was detected, however, of cell surface-associated receptor protein even after 24 hours of IL-2 incubation, suggesting that cytokine induced phosphorylation constitutes a mechanism to regulate receptor activity.
Istvan Toth - One of the best experts on this subject based on the ideXlab platform.
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a drug delivery strategy binding enkephalin to Asialoglycoprotein receptor by enzymatic galactosylation
PLOS ONE, 2014Co-Authors: Michelle P Christie, Pavla Simerska, Waleed M Hussein, Mohamad F M Rawi, Lauren E Hartleytassell, Michael P Jennings, Istvan TothAbstract:Glycosylation of biopharmaceuticals can mediate cell specific delivery by targeting carbohydrate receptors. Additionally, glycosylation can improve the physico-chemical (drug-like) properties of peptide based drug candidates. The main purpose of this study was to examine if glycosylation of the peptide enkephalin could facilitate its binding to the carbohydrate receptor, Asialoglycoprotein. Firstly, we described the one-pot enzymatic galactosylation of lactose modified enkephalin in the presence of uridine-5'-diphosphogalactose 4-epimerase and lipopolysaccharyl alpha-1,4-galactosyltransferase. Stability experiments using human plasma and Caco-2 cell homogenates showed that glycosylation considerably improved the stability of enkephalin (at least 60% remained stable after a 2 hr incubation at 37 degrees C). In vitro permeability experiments using Caco-2 cells revealed that the permeability of mono-and trisaccharide conjugated enkephalins was 14 and 28 times higher, respectively, than that of enkephalin alone (Papp 3.1x10(-8) cm/s). By the methods of surface plasmon resonance and molecular modeling, we demonstrated that the enzymatic glycosylation of enkephalin enabled binding the Asialoglycoprotein receptor. The addition of a trisaccharide moiety to enkephalin improved the binding of enkephalin to the Asialoglycoprotein receptor two fold (K-D=91 mu M). The docking scores from molecular modeling showed that the binding modes and affinities of the glycosylated enkephalin derivatives to the Asialoglycoprotein receptor complemented the results from the surface plasmon resonance experiments.
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A drug delivery strategy: binding enkephalin to Asialoglycoprotein receptor by enzymatic galactosylation
PloS one, 2014Co-Authors: Michelle P Christie, Pavla Simerska, Waleed M Hussein, Mohamad F M Rawi, Michael P Jennings, Freda E.-c. Jen, Lauren E. Hartley-tassell, Christopher J. Day, Istvan TothAbstract:Glycosylation of biopharmaceuticals can mediate cell specific delivery by targeting carbohydrate receptors. Additionally, glycosylation can improve the physico-chemical (drug-like) properties of peptide based drug candidates. The main purpose of this study was to examine if glycosylation of the peptide enkephalin could facilitate its binding to the carbohydrate receptor, Asialoglycoprotein. Firstly, we described the one-pot enzymatic galactosylation of lactose modified enkephalin in the presence of uridine-5′-diphosphogalactose 4-epimerase and lipopolysaccharyl α-1,4-galactosyltransferase. Stability experiments using human plasma and Caco-2 cell homogenates showed that glycosylation considerably improved the stability of enkephalin (at least 60% remained stable after a 2 hr incubation at 37°C). In vitro permeability experiments using Caco-2 cells revealed that the permeability of mono- and trisaccharide conjugated enkephalins was 14 and 28 times higher, respectively, than that of enkephalin alone (Papp 3.1×10−8 cm/s). By the methods of surface plasmon resonance and molecular modeling, we demonstrated that the enzymatic glycosylation of enkephalin enabled binding the Asialoglycoprotein receptor. The addition of a trisaccharide moiety to enkephalin improved the binding of enkephalin to the Asialoglycoprotein receptor two fold (KD = 91 µM). The docking scores from molecular modeling showed that the binding modes and affinities of the glycosylated enkephalin derivatives to the Asialoglycoprotein receptor complemented the results from the surface plasmon resonance experiments.
Robert C. Stadalnik - One of the best experts on this subject based on the ideXlab platform.
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TIPS reduces hepatic Asialoglycoprotein receptor concentration in healthy pigs.
Journal of vascular and interventional radiology : JVIR, 2000Co-Authors: Moni Stein, David R Vera, Robert C. StadalnikAbstract:PURPOSE Technetium-99m-labeled diethylenetriamine pentaacetic acid galactosyl human serum albumin (TcGSA), a new agent for liver scintigraphy, is selectively attached to Asialoglycoprotein receptors on liver cell membranes. A direct correlation exists between Asialoglycoprotein receptor concentration, [R] 0 and hepatic functional reserve. The purpose of this study was to determine the effects of transjugular intrahepatic portosystemic shunting (TIPS) on hepatic Asialoglycoprotein receptor concentration in pigs without liver parenchymal disease. MATERIALS AND METHODS TIPS was performed in eight pigs with use of a single 10-mm-wide × 68-mm-long Wallstent dilated to 10 mm. TcGSA dynamic imaging studies were performed before and twice after (7 and 14 days) TIPS. To be included in the study, pigs had to have a patent TIPS at 1 week of follow-up. Liver function tests were drawn parallel to the TcGSA studies. Liver biopsies were performed at 2 weeks when the animals were killed. RESULTS Five of the eight pigs had open shunts at 1 week and were included in the study. There was a significant ( P t test) difference between the mean [R] o of the pre-TIPS studies ([R] o = 1.12 ± 0.04 μM) and the mean of the post-TIPS studies at 7 days ([R] o = 0.40 ± 0.04 μM) and 14 days ([R] o = 0.51 ± 0.06 μM, P CONCLUSIONS TIPS reduces Asialoglycoprotein receptor concentration in normal pigs.
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In vivo quantification of Asialoglycoprotein receptor.
Methods in enzymology, 1994Co-Authors: Masatoshi Kudo, David R Vera, Robert C. StadalnikAbstract:Publisher Summary This chapter presents a method of in vivo quantification of the Asialoglycoprotein receptor using radiolabeled neoglycoproteins. Technetium-labeled galactosyl neoglycoalbumin (NGA) is a receptorbinding radiopharmaceutical designed for diagnosis of liver disease via kinetic modeling of liver and heart time-activity data. With this radioligand in vivo measurement of Asialoglycoprotein receptor (ASGP-R) biochemistry can be employed. The most relevant quantities pertaining to biochemical function are (1) receptor concentration [R] o that represents the total amount of ASGP-R per liter of hepatic plasma, and (2) the forward binding rate constant kb, which represents the affinity of ASGP-R for the radiolabeled neoglycoprotein.
Toshihiro Akaike - One of the best experts on this subject based on the ideXlab platform.
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Polyethylenimine/arabinogalactan conjugate as a hepatocyte specific gene carrier
Stp Pharma Sciences, 2001Co-Authors: Masayuki Nogawa, Tsutomu Ishihara, Toshihiro Akaike, Atsushi MaruyamaAbstract:Polyethylenimine/arabinogalactan (PEI-AG) conjugates were prepared as a hepatocyte-specific DNA carrier. The conjugates were successfully prepared by reductive amination reaction between the reductive end of arabinogalactan (AG) and amino groups of polyethylenimine using NaBH 3 CN as a catalyst, regardless of the highly branched structure of AG. By changing the AG content in the feed, PEI-AG conjugates containing controlled AG contents were obtained. The conjugates, with AG contents ranging from 47 to 88 weight%, form complexes with plasmid DNA at the same polyethylenimine/DNA ratio. This indicates that AG did not severely affect the interaction between DNA and polyethylenimine moiety in the conjugates. Small DNA complexes (100-200 nm) were formed when plasmid DNA was mixed with PEI-AG conjugates. The complexes maintained dispersive stability in phosphate-buffered saline over a month, indicating that AG moieties contribute to the solubility of the complexes. The surface positive charge of polyethylenimine/DNA complexes decreased with an increase in AG content. The transfection activity of polyethylenimine/DNA complexes toward HeLa or 3T3 cells (Asialoglycoprotein receptors negative) was strongly reduced by AG conjugation whereas that tow ards murine primary hepatocytes (Asialoglycoprotein receptors positive) was preserved. The results indicated that PEI-AG conjugates could avoid the nonspecific interaction with cells while maintaining the high-level transfection efficiency by Asialoglycoprotein receptor-mediated gene expression.
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Culturing hepatocytes on lactose-carrying polystyrene layer via Asialoglycoprotein receptor-mediated interactions.
Methods in enzymology, 1994Co-Authors: Kazukiyo Kobayashi, Akira Kobayashi, Toshihiro AkaikeAbstract:Publisher Summary This chapter discusses the preparation of lactosecarrying polystyrene (PVLA) and the culture of hepatocytes using PVLA as substratum which can interact specifically and strongly with Asialoglycoprotein receptors on the surface of mammalian liver cells. Design of bio-functional materials employing specific combinations between ligands on synthetic polymers and receptors on cell surfaces is a promising approach to construct fascinating biomedical systems for cell separations, cell cultures, drug delivery agents, artificial antigens, and so on. Carbohydrate is one of the most important candidates as ligands or recognition signals. Interactions of hepatocytes with PVLA were similar in some aspects to those with Asialoglycoproteins, their oligosaccharides, and neoglycoproteins.
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Determination of mouse major Asialoglycoprotein receptor cDNA sequence.
Biochimica et biophysica acta, 1993Co-Authors: Ryuichi Takezawa, Kouei Shinzawa, Yoshifumi Watanabe, Toshihiro AkaikeAbstract:Hepatic lectins (Asialoglycoprotein receptors) specifically recognize galactose-terminated glycoproteins and mediate endocytosis of these molecules. We now report the cloning and sequence of a cDNA encoding murine Asialoglycoprotein receptor. It shows high homology with rat and human major receptor forms designated RHL-1 and HHL-1, respectively. They have many conserved regions, such as a transmembrane region, carbohydrate additional region and carbohydrate related region. According to the homology analysis, we concluded that the clone encodes the mouse major Asialoglycoprotein receptor (MHL-1).
Michelle P Christie - One of the best experts on this subject based on the ideXlab platform.
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a drug delivery strategy binding enkephalin to Asialoglycoprotein receptor by enzymatic galactosylation
PLOS ONE, 2014Co-Authors: Michelle P Christie, Pavla Simerska, Waleed M Hussein, Mohamad F M Rawi, Lauren E Hartleytassell, Michael P Jennings, Istvan TothAbstract:Glycosylation of biopharmaceuticals can mediate cell specific delivery by targeting carbohydrate receptors. Additionally, glycosylation can improve the physico-chemical (drug-like) properties of peptide based drug candidates. The main purpose of this study was to examine if glycosylation of the peptide enkephalin could facilitate its binding to the carbohydrate receptor, Asialoglycoprotein. Firstly, we described the one-pot enzymatic galactosylation of lactose modified enkephalin in the presence of uridine-5'-diphosphogalactose 4-epimerase and lipopolysaccharyl alpha-1,4-galactosyltransferase. Stability experiments using human plasma and Caco-2 cell homogenates showed that glycosylation considerably improved the stability of enkephalin (at least 60% remained stable after a 2 hr incubation at 37 degrees C). In vitro permeability experiments using Caco-2 cells revealed that the permeability of mono-and trisaccharide conjugated enkephalins was 14 and 28 times higher, respectively, than that of enkephalin alone (Papp 3.1x10(-8) cm/s). By the methods of surface plasmon resonance and molecular modeling, we demonstrated that the enzymatic glycosylation of enkephalin enabled binding the Asialoglycoprotein receptor. The addition of a trisaccharide moiety to enkephalin improved the binding of enkephalin to the Asialoglycoprotein receptor two fold (K-D=91 mu M). The docking scores from molecular modeling showed that the binding modes and affinities of the glycosylated enkephalin derivatives to the Asialoglycoprotein receptor complemented the results from the surface plasmon resonance experiments.
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A drug delivery strategy: binding enkephalin to Asialoglycoprotein receptor by enzymatic galactosylation
PloS one, 2014Co-Authors: Michelle P Christie, Pavla Simerska, Waleed M Hussein, Mohamad F M Rawi, Michael P Jennings, Freda E.-c. Jen, Lauren E. Hartley-tassell, Christopher J. Day, Istvan TothAbstract:Glycosylation of biopharmaceuticals can mediate cell specific delivery by targeting carbohydrate receptors. Additionally, glycosylation can improve the physico-chemical (drug-like) properties of peptide based drug candidates. The main purpose of this study was to examine if glycosylation of the peptide enkephalin could facilitate its binding to the carbohydrate receptor, Asialoglycoprotein. Firstly, we described the one-pot enzymatic galactosylation of lactose modified enkephalin in the presence of uridine-5′-diphosphogalactose 4-epimerase and lipopolysaccharyl α-1,4-galactosyltransferase. Stability experiments using human plasma and Caco-2 cell homogenates showed that glycosylation considerably improved the stability of enkephalin (at least 60% remained stable after a 2 hr incubation at 37°C). In vitro permeability experiments using Caco-2 cells revealed that the permeability of mono- and trisaccharide conjugated enkephalins was 14 and 28 times higher, respectively, than that of enkephalin alone (Papp 3.1×10−8 cm/s). By the methods of surface plasmon resonance and molecular modeling, we demonstrated that the enzymatic glycosylation of enkephalin enabled binding the Asialoglycoprotein receptor. The addition of a trisaccharide moiety to enkephalin improved the binding of enkephalin to the Asialoglycoprotein receptor two fold (KD = 91 µM). The docking scores from molecular modeling showed that the binding modes and affinities of the glycosylated enkephalin derivatives to the Asialoglycoprotein receptor complemented the results from the surface plasmon resonance experiments.
