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Asialoglycoprotein receptor

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https://www.readbyqxmd.com/read/27895355/prediction-of-asialoglycoprotein-receptors-by-correlated-liver-function-parameters-before-hepatectomy
#1
Wen Jing, Jiang Li, Li Qin Tao, Jia Zhe, Li Bao Liang, Zhang Ke
Flow cytometric analysis of asialoglycoprotein receptor (ASGPR) levels on the surface of hepatocytes, which were obtained from the liver specimens of patients that received hepatectomy, were used as predictors of liver dysfunction after major hepatectomy for primary hepatocellular carcinoma (HCC) in Chinese patients, based on our previous study which confirmed the value of ASGPR levels on the surface of hepatocytes in evaluating the liver reserve function. The current study was planned to establish a conversion formula for the value of ASGPR with correlated liver function parameters...
October 2016: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/27748959/study-of-ethanol-induced-golgi-disorganization-reveals-the-potential-mechanism-of-alcohol-impaired-n-glycosylation
#2
Carol A Casey, Ganapati Bhat, Melissa S Holzapfel, Armen Petrosyan
BACKGROUND: It is known that ethanol (EtOH) and its metabolites have a negative effect on protein glycosylation. The fragmentation of the Golgi apparatus induced by alteration of the structure of largest Golgi matrix protein, giantin, is the major consequence of damaging effects of EtOH-metabolism on the Golgi; however, the link between this and abnormal glycosylation remains unknown. Because previously we have shown that Golgi morphology dictates glycosylation, we examined the effect EtOH administration has on function of Golgi residential enzymes involved in N-glycosylation...
December 2016: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/27732771/n-glycan-truncation-causes-enhanced-clearance-of-plasma-derived-von-willebrand-factor
#3
Jamie M O'Sullivan, Sonia Aguila, Emily McRae, Soracha E Ward, Orla Rawley, Padraic G Fallon, Teresa M Brophy, Roger J S Preston, Lauren Brady, Orla Sheils, Alain Chion, James S O'Donnell
BACKGROUND: Enhanced von Willebrand factor (VWF) clearance is important in the etiology of both type 1 and type 2 von Willebrand disease (VWD). In addition, previous studies have demonstrated that VWF glycans play a key role in regulating in vivo clearance. However, the molecular mechanisms underlying VWF clearance remain poorly understood. OBJECTIVE: To define the molecular mechanisms through which VWF N-glycan structures influence in vivo clearance. METHODS: Using a series of exoglycosidases, different pd-VWF glycoforms were generated...
October 12, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27702535/fabrication-of-stable-galactosylated-alginate-microcapsules-via-covalent-coupling-onto-hydroxyl-groups-for-hepatocytes-applications
#4
Ruyun Lou, Weiting Yu, Yizhe Song, Ying Ren, Huizhen Zheng, Xin Guo, Yunfei Lin, Guoyu Pan, Xiuli Wang, Xiaojun Ma
Galactose moieties are covalently coupled with sodium alginate to enhance liver-specific functions in microcapsules owing to the specific interaction between the galactose moieties and the asialoglycoprotein receptors (ASGPRs) of hepatocytes. In this study, galactosylated alginate (L-NH2-OH-alginate) based microcapsules with desirable stability and a suitable 3D microenvironment are designed and fabricated for primary hepatocyte applications. The designed L-NH2-OH-alginate is fabricated via the application of ethylenediamine grafted lactobionic acid (L-NH2) onto the hydroxyl groups of sodium alginate so that the negatively charged carboxyl groups intact in L-NH2-OH-alginate can effectively bond with Ca(2+) to form a stable three-dimensional gel network; a subsequent reaction with polycations forms a stable membrane of microcapsules...
January 2, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/27667543/alginate-based-microcapsules-with-galactosylated-chitosan-internal-for-primary-hepatocyte-applications
#5
Ruyun Lou, Hongguo Xie, Huizhen Zheng, Ying Ren, Meng Gao, Xin Guo, Yizhe Song, Weiting Yu, Xiudong Liu, Xiaojun Ma
Alginate-galactosylated chitosan/polylysine (AGCP) microcapsules with excellent stability and high permeability were developed and employed in primary hepatocyte applications. The galactosylated chitosan (GC), synthesized via the covalent coupling of lactobionic acid (LA) with low molecular weight and water-soluble chitosan (CS), was ingeniously introduced into the core of alginate microcapsules by regulating the pH of gelling bath. The internal GC of the microcapsules simultaneously provided a large number of binding sites for the hepatocytes and further promoted the hepatocyte-matrix interactions via the recognition of asialoglycoprotein receptors (ASGPRs) on the hepatocyte surface, and afforded the AGCP microcapsules an excellent stability via the electrostatic interactions with alginate...
September 22, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27662377/microfluidic-chip-for-isolation-of-viable-circulating-tumor-cells-of-hepatocellular-carcinoma-for-their-culture-and-drug-sensitivity-assay
#6
Yu Zhang, Xiaofeng Zhang, Jinling Zhang, Bin Sun, Lulu Zheng, Jun Li, Sixiu Liu, Guodong Sui, Zhengfeng Yin
Circulating tumor cells (CTCs) have been proposed to be an active source of metastasis or recurrence of hepatocellular carcinoma (HCC). The enumeration and characterization of CTCs has important clinical significance in recurrence prediction and treatment monitoring in HCC patients. We previously developed a unique method to separate HCC CTCs based on the interaction of the asialoglycoprotein receptor (ASGPR) expressed on their membranes with its ligand. The current study applied the ligand-receptor binding assay to a CTC-chip in a microfluidic device...
September 23, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27643636/fabrication-of-3d-culture-platform-with-sandwich-architecture-for-preserving-liver-specific-functions-of-hepatocytes-using-3d-bioprinter
#7
Kenichi Arai, Toshiko Yoshida, Motonori Okabe, Mitsuaki Goto, Tanveer Ahmad Mir, Chika Soko, Yoshinari Tsukamoto, Toshihiro Akaike, Toshio Nikaido, Kaixuan Zhou, Makoto Nakamura
The development of new three-dimensional (3D) cell culture system that maintains the physiologically relevant signals of hepatocytes is essential in drug discovery and tissue engineering research. Conventional two-dimensional (2D) culture yields cell growth, proliferation and differentiation. However, gene expression and signaling profiles can be different from in vivo environment. Here, we report the fabrication of a 3D culture system using an artificial scaffold and our custom-made inkjet 3D-bioprinter as a new strategy for studying liver-specific functions of hepatocytes...
September 19, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/27542278/kukoamine-b-promotes-tlr4-independent-lipopolysaccharide-uptake-in-murine-hepatocytes
#8
Dong Yang, Xinchuan Zheng, Ning Wang, Shijun Fan, Yongjun Yang, Yongling Lu, Qian Chen, Xin Liu, Jiang Zheng
Free bacterial lipopolysaccharide (LPS) is generally removed from the bloodstream through hepatic uptake via TLR4, the LPS pattern recognition receptor, but mechanisms for internalization and clearance of conjugated LPS are less clear. Kukoamine B (KB) is a novel cationic alkaloid that interferes with LPS binding to TLR4. In this study, KB accelerated blood clearance of LPS. KB also enhanced LPS distribution in the hepatic tissues of C57 BL/6 mice, along with LPS uptake in primary hepatocytes and HepG2 cells...
August 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27440073/identification-of-novel-small-molecule-asgp-r-ligands
#9
Alexander G Majouga, Yan A Ivanenkov, Mark S Veselov, Anton V Lopuhov, Svetlana V Maklakova, Elena K Beloglazkina, Natalya L Klyachko, Yuri B Sandulenko, Natalia Y Galkina, Victor E Koteliansky
During the past decade asialoglycoprotein receptor (ASGP-R) expressed predominantly by hepatocytes has attracted a considerable attention as a convenient biomolecular trap for targeted drug delivery. Currently, several selective galactose-containing ligands equipped by drug molecules, e.g. known anticancer therapeutics, as well as diagnostic tools are under active preclinical development. In this paper, we have carried out a rational in silico screening among the molecules available in ChemDiv collection and compounds provided by our colleagues to reveal potential ASGP-R binders...
July 19, 2016: Current Drug Delivery
https://www.readbyqxmd.com/read/27405760/functional-consequences-of-mannose-and-asialoglycoprotein-receptor-ablation
#10
Yiling Mi, Marcy Coonce, Dorothy Fiete, Lindsay Steirer, Gabriela Dveksler, R Reid Townsend, Jacques U Baenziger
The mannose receptor (ManR, Mrc1) and asialoglycoprotein receptor (ASGR, Asgr1 and Asgr2) are highly abundant endocytic receptors expressed by sinusoidal endothelial cells and parenchymal cells in the liver, respectively. We genetically manipulated either receptor individually or in combination, revealing phenotypic changes in female and male mice associated with changes in circulating levels of many glycoproteins. Both receptors rise and fall in response to progesterone during pregnancy. Thirty percent of Asgr2(-/-) and 65% of Mrc1(-/-)Asgr2(-/-) mice are unable to initiate parturition at the end of pregnancy, whereas Mrc1(-/-) mice initiate normally...
September 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27377130/simultaneous-spect-imaging-of-multi-targets-to-assist-in-identifying-hepatic-lesions
#11
Zhide Guo, Mengna Gao, Deliang Zhang, Yesen Li, Manli Song, Rongqiang Zhuang, Xinhui Su, Guibing Chen, Ting Liu, Pingguo Liu, Hua Wu, Jin Du, Xianzhong Zhang
Molecular imaging technique is an attractive tool to detect liver disease at early stage. This study aims to develop a simultaneous dual-isotope single photon emission computed tomography (SPECT)/CT imaging method to assist diagnosis of hepatic tumor and liver fibrosis. Animal models of liver fibrosis and orthotopic human hepatocellular carcinoma (HCC) were established. The tracers of (131)I-NGA and (99m)Tc-3P-RGD2 were selected to target asialoglycoprotein receptor (ASGPR) on the hepatocytes and integrin αvβ3 receptor in tumor or fibrotic liver, respectively...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27321376/cd8-t-cells-induce-platelet-clearance-in-the-liver-via-platelet-desialylation-in-immune-thrombocytopenia
#12
Jihua Qiu, Xuena Liu, Xiaoqing Li, Xu Zhang, Panpan Han, Hai Zhou, Linlin Shao, Yu Hou, Yanan Min, Zhangyuan Kong, Yawen Wang, Yu Wei, Xinguang Liu, Heyu Ni, Jun Peng, Ming Hou
In addition to antiplatelet autoantibodies, CD8(+) cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8(+) T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8(+) T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8(+) T cells than those without cytotoxicity and controls...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27287244/galactose-containing-polymer-dox-conjugates-for-targeting-drug-delivery
#13
Yujie Sun, Jing Zhang, Jian Han, Baocheng Tian, Yanan Shi, Yuanyuan Ding, Lele Wang, Jingtian Han
A novel multifunctional drug delivery system was fabricated by conjugating galactose-based polymer, methoxy-poly(ethylene glycol)-block-poly(6-O-methacryloyl-D-galactopyranose) (mPEG-b-PMAGP) with doxorubicin (DOX) via an acid-labile carbamate linkage. The mPEG-b-PMAGP-co-DOX nanoparticles were spherical in shape, and the diameter determined by dynamic light scattering (DLS) was 54.84 ± 0.58 nm, larger than that characterized by transmission electron microscopy (TEM). The in vitro drug release profiles were studied, and the release of DOX from the nanoparticles was pH-responsive...
June 10, 2016: AAPS PharmSciTech
https://www.readbyqxmd.com/read/27268307/conjugation-of-mono-and-di-galnac-sugars-enhances-the-potency-of-antisense-oligonucleotides-via-asgr-mediated-delivery-to-hepatocytes
#14
Garth A Kinberger, Thazha P Prakash, Jinghua Yu, Guillermo Vasquez, Audrey Low, Alfred Chappell, Karsten Schmidt, Heather M Murray, Hans Gaus, Eric E Swayze, Punit P Seth
Antisense oligonucleotides (ASOs) conjugated to trivalent GalNAc ligands show 10-fold enhanced potency for suppressing gene targets expressed in hepatocytes. Trivalent GalNAc is a high affinity ligand for the asialoglycoprotein receptor (ASGR)-a C-type lectin expressed almost exclusively on hepatocytes in the liver. In this communication, we show that conjugation of two and even one GalNAc sugar to single stranded chemically modified ASOs can enhance potency 5-10 fold in mice. Evaluation of the mono- and di-GalNAc ASO conjugates in an ASGR binding assay suggested that chemical features of the ASO enhance binding to the receptor and provide a rationale for the enhanced potency...
August 1, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27241665/the-asialoglycoprotein-receptor-suppresses-the-metastasis-of-hepatocellular-carcinoma-via-lass2-mediated-inhibition-of-v-atpase-activity
#15
Dishui Gu, Haojie Jin, Guangzhi Jin, Cun Wang, Ning Wang, Fangyuan Hu, Qin Luo, Wei Chu, Ming Yao, Wenxin Qin
The asialoglycoprotein receptor (ASGR), which is expressed mainly in hepatocytes, is downregulated in poorly differentiated hepatocellular carcinoma (HCC). Here we investigated the role of ASGR1 in HCC metastasis as well as the possible underlying molecular mechanisms. We found that ASGR1 was downregulated in HCC tissue compared with adjacent non-tumorous liver tissue and that lower ASGR1 expression was associated with higher TNM stage and poorer prognosis in HCC patients. ASGR1 overexpression inhibited hepatoma cell migration and invasion in vitro and in vivo, while ASGR1 knockdown had the opposite effects...
August 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27231122/design-of-cholesterol-arabinogalactan-anchored-liposomes-for-asialoglycoprotein-receptor-mediated-targeting-to-hepatocellular-carcinoma-in-silico-modeling-in-vitro-and-in-vivo-evaluation
#16
Pankaj Pathak, Vivek Dhawan, Aniket Magarkar, Reinis Danne, Srinath Govindarajan, Sandipto Ghosh, Frank Steiniger, Pradip Chaudhari, Vijaya Gopal, Alex Bunker, Tomasz Róg, Alfred Fahr, Mangal Nagarsenker
We have developed active targeting liposomes to deliver anticancer agents to ASGPR which will contribute to effective treatment of hepatocellular carcinoma. Active targeting is achieved through polymeric ligands on the liposome surface. The liposomes were prepared using reverse phase evaporation method and doxorubicin hydrocholoride, a model drug, was loaded using the ammonium sulphate gradient method. Liposomes loaded with DOX were found to have a particle size of 200nm with more than 90% entrapment efficiency...
July 25, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27192541/variant-asgr1-associated-with-a-reduced-risk-of-coronary-artery-disease
#17
Paul Nioi, Asgeir Sigurdsson, Gudmar Thorleifsson, Hannes Helgason, Arna B Agustsdottir, Gudmundur L Norddahl, Anna Helgadottir, Audur Magnusdottir, Aslaug Jonasdottir, Solveig Gretarsdottir, Ingileif Jonsdottir, Valgerdur Steinthorsdottir, Thorunn Rafnar, Dorine W Swinkels, Tessel E Galesloot, Niels Grarup, Torben Jørgensen, Henrik Vestergaard, Torben Hansen, Torsten Lauritzen, Allan Linneberg, Nele Friedrich, Nikolaj T Krarup, Mogens Fenger, Ulrik Abildgaard, Peter R Hansen, Anders M Galløe, Peter S Braund, Christopher P Nelson, Alistair S Hall, Michael J A Williams, Andre M van Rij, Gregory T Jones, Riyaz S Patel, Allan I Levey, Salim Hayek, Svati H Shah, Muredach Reilly, Gudmundur I Eyjolfsson, Olof Sigurdardottir, Isleifur Olafsson, Lambertus A Kiemeney, Arshed A Quyyumi, Daniel J Rader, William E Kraus, Nilesh J Samani, Oluf Pedersen, Gudmundur Thorgeirsson, Gisli Masson, Hilma Holm, Daniel Gudbjartsson, Patrick Sulem, Unnur Thorsteinsdottir, Kari Stefansson
BACKGROUND: Several sequence variants are known to have effects on serum levels of non-high-density lipoprotein (HDL) cholesterol that alter the risk of coronary artery disease. METHODS: We sequenced the genomes of 2636 Icelanders and found variants that we then imputed into the genomes of approximately 398,000 Icelanders. We tested for association between these imputed variants and non-HDL cholesterol levels in 119,146 samples. We then performed replication testing in two populations of European descent...
June 2, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27192165/the-sialylation-pathway-and-coronary-artery-disease
#18
EDITORIAL
Anne Tybjærg-Hansen
No abstract text is available yet for this article.
June 2, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27164023/elucidation-of-the-biotransformation-pathways-of-a-galnac3-conjugated-antisense-oligonucleotide-in-rats-and-monkeys
#19
Colby S Shemesh, Rosie Z Yu, Hans J Gaus, Sarah Greenlee, Noah Post, Karsten Schmidt, Michael T Migawa, Punit P Seth, Thomas A Zanardi, Thazha P Prakash, Eric E Swayze, Scott P Henry, Yanfeng Wang
Triantennary N-acetyl galactosamine (GalNAc3) is a high-affinity ligand for hepatocyte-specific asialoglycoprotein receptors. Conjugation with GalNAc3 via a trishexylamino (THA)-C6 cluster significantly enhances antisense oligonucleotide (ASO) potency. Herein, the biotransformation, disposition, and elimination of the THA cluster of ION-681257, a GalNAc3-conjugated ASO currently in clinical development, are investigated in rats and monkey. Rats were administered a single subcutaneous dose of (3)H-radiolabeled ((3)H placed in THA) or nonradiolabeled ION-681257...
2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27159903/superfluorinated-pei-derivative-coupled-with-99m-tc-for-asgpr-targeted-19-f-mri-spect-pa-tri-modality-imaging
#20
Zhide Guo, Mengna Gao, Manli Song, Yesen Li, Deliang Zhang, Duo Xu, Linyi You, Liangliang Wang, Rongqiang Zhuang, Xinhui Su, Ting Liu, Jin Du, Xianzhong Zhang
Fluorinated polyethylenimine derivative labeled with radionuclide (99m) Tc is developed as a (19) F MRI/SPECT/PA multifunctional imaging agent with good asialoglycoprotein receptors (ASGPR)-targeting ability. This multifunctional agent is safe and suitable for (19) F MRI/SPECT/PA imaging and has the potential to detect hepatic diseases and to assess liver function, which provide powerful support for the development of personalized and precision medicine.
July 2016: Advanced Materials
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