Synthesis and release of chondroitin sulphate and heparan sulphate proteoglycans from mouse macrophagesin vitro

1987 ◽  
Vol 4 (1) ◽  
pp. 73-84 ◽  
Author(s):  
Svein O Kolset
Keyword(s):  
Chondroitin Sulphate ◽  
Heparan Sulphate ◽  
Heparan Sulphate Proteoglycans

Heparan sulphate proteoglycans and spinal neurulation in the mouse embryo

Development ◽  
2002 ◽  
Vol 129 (9) ◽  
pp. 2109-2119 ◽  
Author(s):  
George W. Yip ◽  
Patrizia Ferretti ◽  
Andrew J. Copp
Keyword(s):  
Sonic Hedgehog ◽  
Chondroitin Sulphate ◽  
Heparan Sulphate ◽  
In Situ Hybridisation ◽  
Competitive Inhibitor ◽  
Cellular Growth ◽  
Posterior Neuropore ◽  
Heparan Sulphate Proteoglycans ◽  
Hinge Points ◽  
Patched 1

Heparan sulphate proteoglycans have been implicated in the binding and presentation of several growth factors to their receptors, thereby regulating cellular growth and differentiation. To investigate the role of heparan sulphate proteoglycans in mouse spinal neurulation, we administered chlorate, a competitive inhibitor of glycosaminoglycan sulphation, to cultured E8.5 embryos. Treated embryos exhibit accelerated posterior neuropore closure, accompanied by suppression of neuroepithelial bending at the median hinge point and accentuated bending at the paired dorsolateral hinge points of the posterior neuropore. These effects appear specific, as they can be prevented by addition of heparan sulphate to the culture medium, whereas heparitinase-treated heparan sulphate and chondroitin sulphate are ineffective. Both N- and O-sulphate groups appear to be necessary for the action of heparan sulphate. In situ hybridisation analysis demonstrates a normal distribution of sonic hedgehog mRNA in chlorate-treated embryos. By contrast, patched 1 transcripts are abnormally abundant in the notochord, and diminished in the overlying neuroepithelium, suggesting that sonic hedgehog signalling from the notochord may be perturbed by inhibition of heparan sulphation. Together, these results demonstrate a regulatory role for heparan sulphate in mouse spinal neurulation.

scholarly journals Proteoglycan involvement in polyamine uptake

1999 ◽  
Vol 338 (2) ◽  
pp. 317-323 ◽  
Author(s):  
Mattias BELTING ◽  
Susanne PERSSON ◽  
Lars-Åke FRANSSON
Keyword(s):  
Chondroitin Sulphate ◽  
Heparan Sulphate ◽  
Chinese Hamster ◽  
Selective Inhibition ◽  
Lung Fibroblasts ◽  
Ovary Cell ◽  
Wild Type ◽  
Polyamine Biosynthesis ◽  
Heparan Sulphate Proteoglycans ◽  
Mutant Cells

We have evaluated the possible role of proteoglycans in the uptake of spermine by human lung fibroblasts. Exogenous glycosaminoglycans behaved as competitive inhibitors of spermine uptake, the most efficient being heparan sulphate (Ki = 0.16±0.04 µM). Treatment of fibroblasts with either heparan sulphate lyase, p-nitrophenyl-O-β-d-xylopyranoside or chlorate reduced spermine uptake considerably, whereas chondroitin sulphate lyase had a limited effect. Inhibition of polyamine biosynthesis with α-difluoromethylornithine resulted in an increase of cell-associated heparan sulphate proteoglycans exhibiting higher affinity for spermine. The data indicate a specific role for heparan sulphate proteoglycans in the uptake of spermine by fibroblasts. Spermine uptake by pgsD-677, a mutant Chinese hamster ovary cell defective in heparan sulphate biosynthesis, was only moderately reduced (20%) compared with wild-type cells. Treatment of mutant cells with the above-mentioned xyloside resulted in a greater reduction of endogenous proteoglycan production as well as a higher inhibition of spermine uptake than in wild-type cells. Moreover, treatment with chondroitin sulphate lyase resulted in a selective inhibition of uptake in mutant cells, indicating a role for chondroitin/dermatan sulphate proteoglycans in the uptake of spermine by these cells. Fibroblasts, made growth-dependent on exogenous spermine by α-difluoromethylornithine treatment, were growth-inhibited by heparan sulphate or β-d-xyloside, which might have future therapeutical implications.

scholarly journals What Are the Potential Roles of Nuclear Perlecan and Other Heparan Sulphate Proteoglycans in the Normal and Malignant Phenotype

2021 ◽  
Vol 22 (9) ◽  
pp. 4415
Author(s):  
Anthony J. Hayes ◽  
James Melrose
Keyword(s):  
Gene Expression ◽  
Nuclear Envelope ◽  
Annulus Fibrosus ◽  
Heparan Sulphate ◽  
Cell Types ◽  
Malignant Cell ◽  
Cytoskeletal Proteins ◽  
Nucleus Pulposus Cells ◽  
Malignant Phenotype ◽  
Heparan Sulphate Proteoglycans

The recent discovery of nuclear and perinuclear perlecan in annulus fibrosus and nucleus pulposus cells and its known matrix stabilizing properties in tissues introduces the possibility that perlecan may also have intracellular stabilizing or regulatory roles through interactions with nuclear envelope or cytoskeletal proteins or roles in nucleosomal-chromatin organization that may regulate transcriptional factors and modulate gene expression. The nucleus is a mechano-sensor organelle, and sophisticated dynamic mechanoresponsive cytoskeletal and nuclear envelope components support and protect the nucleus, allowing it to perceive and respond to mechano-stimulation. This review speculates on the potential roles of perlecan in the nucleus based on what is already known about nuclear heparan sulphate proteoglycans. Perlecan is frequently found in the nuclei of tumour cells; however, its specific role in these diseased tissues is largely unknown. The aim of this review is to highlight probable roles for this intriguing interactive regulatory proteoglycan in the nucleus of normal and malignant cell types.

Heparan sulphate proteoglycans in Alzheimer's disease and amyloid‐related disorders

2003 ◽  
Vol 2 (8) ◽  
pp. 482-492 ◽  
Author(s):  
Jack van Horssen ◽  
Pieter Wesseling ◽  
Lambert PWJ van den Heuvel ◽  
Robert MW de Waal ◽  
Marcel M Verbeek
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heparan Sulphate ◽  
Heparan Sulphate Proteoglycans

scholarly journals Glycosaminoglycans on fibroblasts accelerate thrombin inhibition by protease nexin-1

1987 ◽  
Vol 245 (2) ◽  
pp. 543-550 ◽  
Author(s):  
D H Farrell ◽  
D D Cunningham
Keyword(s):  
Complex Formation ◽  
Cell Surface ◽  
Plasma Membranes ◽  
Chondroitin Sulphate ◽  
Human Fibroblasts ◽  
Heparan Sulphate ◽  
Order Rate Constant ◽  
Subsequent Treatment ◽  
Protease Nexin ◽  
Inhibition Of Thrombin

Protease nexin-1 (PN-1) is a proteinase inhibitor that is secreted by human fibroblasts in culture. PN-1 inhibits certain regulatory serine proteinases by forming a covalent complex with the catalytic-site serine residue; the complex then binds to the cell surface and is internalized and degraded. The fibroblast surface was recently shown to accelerate the rate of complex-formation between PN-1 and thrombin. The present paper demonstrates that the accelerative activity is primarily due to cell-surface heparan sulphate, with a much smaller contribution from chondroitin sulphate. This conclusion is supported by the effects of purified glycosaminoglycans on the second-order rate constant for the inhibition of thrombin by PN-1. Also, treatment of 35SO4(2-)-labelled cells with heparitin sulphate lyase or chondroitin sulphate ABC lyase demonstrated two discrete pools of 35S-labelled glycosaminoglycans; subsequent treatment of plasma membranes with these glycosidases showed that heparitin sulphate lyase treatment abolished about 80% of the accelerative activity and chondroitin sulphate ABC lyase removed the remaining 20%. These results show that two components are responsible for the acceleration of PN-1-thrombin complex-formation by human fibroblasts. Although dermatan sulphate is also present on fibroblasts, it did not accelerate the inhibition of thrombin by PN-1.

Localisation and characterization of acid mucopolysaccharides in the early chick blastoderm

Development ◽  
1980 ◽  
Vol 56 (1) ◽  
pp. 169-178
Author(s):  
Ch. Vanroelen ◽  
L. Vakaet ◽  
L. Andries
Keyword(s):  
Chondroitin Sulphate ◽  
Heparan Sulphate ◽  
Middle Layer ◽  
Ventral Side ◽  
Chick Blastoderm ◽  
Cellulose Acetate Electrophoresis ◽  
Acid Mucopolysaccharides ◽  
Extracellular Compartment ◽  
Early Specialization ◽  
Testicular Hyaluronidase

Acid mucopolysaccharides in the extracellular compartment of early chick blastoderms (16 h of incubation) were labelled with tritiated glucosamine and/or ]35S]sulphate. The incorporation pattern was studied autoradiographically. Treatment with testicular hyaluronidase revealed a testicular hyaluronidase-sensitive fraction, mainly at the periphery of Middle Layer and Deep Layer cells, and a testicular hyaluronidase-resistant fraction, mainly at the ventral side of the Upper Layer. A biochemical analysis, utilizing chondroitinase ABC and nitrous acid, followed by cellulose acetate electrophoresis, demonstrated the synthesis of a non-sulphated fraction, i.e. hyaluronic acid and/or chondroitin, and a sulphated fraction, comprising two undersulphated components, i.e. chondroitin sulphate, and heparan sulphate or heparin. The appearance of different AMPS in specific areas of the early chick blastoderm is regarded as an early specialization of the extracellular compartment.

scholarly journals Recent Insights into Cell Surface Heparan Sulphate Proteoglycans and Cancer

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1541 ◽  
Author(s):  
John R Couchman ◽  
Hinke Multhaupt ◽  
Ralph D. Sanderson
Keyword(s):  
Cell Surface ◽  
Core Protein ◽  
Tumour Progression ◽  
Heparan Sulphate ◽  
Cell Behaviour ◽  
Surface Receptors ◽  
Protein Ligands ◽  
Proliferation And Differentiation ◽  
Cell Processes ◽  
Heparan Sulphate Proteoglycans

A small group of cell surface receptors are proteoglycans, possessing a core protein with one or more covalently attached glycosaminoglycan chains. They are virtually ubiquitous and their chains are major sites at which protein ligands of many types interact. These proteoglycans can signal and regulate important cell processes, such as adhesion, migration, proliferation, and differentiation. Since many protein ligands, such as growth factors, morphogens, and cytokines, are also implicated in tumour progression, it is increasingly apparent that cell surface proteoglycans impact tumour cell behaviour. Here, we review some recent advances, emphasising that many tumour-related functions of proteoglycans are revealed only after their modification in processes subsequent to synthesis and export to the cell surface. These include enzymes that modify heparan sulphate structure, recycling of whole or fragmented proteoglycans into exosomes that can be paracrine effectors or biomarkers, and lateral interactions between some proteoglycans and calcium channels that impact the actin cytoskeleton.

Dermatan sulphate promotes neuronal differentiation in mouse and human stem cells

2020 ◽  
Author(s):  
Chika Ogura ◽  
Kazumi Hirano ◽  
Shuji Mizumoto ◽  
Shuhei Yamada ◽  
Shoko Nishihara
Keyword(s):  
Stem Cells ◽  
Neurite Outgrowth ◽  
Neuronal Differentiation ◽  
Neural Progenitor Cells ◽  
Chondroitin Sulphate ◽  
Heparan Sulphate ◽  
Embryonic Stem ◽  
Hydroxyl Group ◽  
Human Stem Cells ◽  
Dermatan Sulphate

Abstract Dermatan sulphate (DS), a glycosaminoglycan, is present in the extracellular matrix and on the cell surface. Previously, we showed that heparan sulphate plays a key role in the maintenance of the undifferentiated state in mouse embryonic stem cells (mESCs) and in the regulation of their differentiation. Chondroitin sulphate has also been to be important for pluripotency and differentiation of mESCs. Keratan sulphate is a marker of human pluripotent stem cells. To date, however, the function of DS in mESCs has not been clarified. Dermatan 4 sulfotransferase 1, which transfers sulphate to the C-4 hydroxyl group of N-acetylgalactosamine of DS, contributes to neuronal differentiation of mouse neural progenitor cells. Therefore, we anticipated that neuronal differentiation would be induced in mESCs in culture by the addition of DS. To test this expectation, we investigated neuronal differentiation in mESCs and human neural stem cells (hNSCs) cultures containing DS. In mESCs, DS promoted neuronal differentiation by activation of extracellular signal-regulated kinase 1/2 and also accelerated neurite outgrowth. In hNSCs, DS promoted neuronal differentiation and neuronal migration, but not neurite outgrowth. Thus, DS promotes neuronal differentiation in both mouse and human stem cells, suggesting that it offers a novel method for efficiently inducing neuronal differentiation.

scholarly journals Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry

2015 ◽  
Vol 13 (4) ◽  
pp. 510-517 ◽  
Author(s):  
Ana Paula Cleto Marolla ◽  
Jaques Waisberg ◽  
Gabriela Tognini Saba ◽  
Daniel Reis Waisberg ◽  
Fernando Beani Margeotto ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Electrospray Ionization ◽  
Electrospray Ionization Mass Spectrometry ◽  
Chondroitin Sulphate ◽  
Heparan Sulphate ◽  
Ionization Mass Spectrometry ◽  
Ionization Mass ◽  
Neoplastic Tissue ◽  
Colorectal Tissue ◽  
Neoplastic Tissues

ABSTRACT Objective To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Methods Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student’st test. Results The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). Conclusion The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues.

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