scholarly journals Synthesis of 3-O-Sulfated Oligosaccharides to Understand the Relationship between Structures and Functions of Heparan Sulfate

2017 ◽  
Vol 139 (14) ◽  
pp. 5249-5256 ◽  
Author(s):  
Zhangjie Wang ◽  
Po-Hung Hsieh ◽  
Yongmei Xu ◽  
David Thieker ◽  
Evangeline Juan En Chai ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Sulfated Oligosaccharides ◽  
The Relationship

scholarly journals Heparan Sulfate Proteoglycans May Promote or Inhibit Cancer Progression by Interacting with Integrins and Affecting Cell Migration

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Mariana A. Soares ◽  
Felipe C. O. B. Teixeira ◽  
Miguel Fontes ◽  
Ana Lúcia Arêas ◽  
Marcelo G. Leal ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Cancer Progression ◽  
Heparan Sulfate Proteoglycans ◽  
Transmembrane Receptors ◽  
Surface Molecules ◽  
Cell Matrix ◽  
Cell Organization ◽  
The Relationship

The metastatic disease is one of the main consequences of tumor progression, being responsible for most cancer-related deaths worldwide. This review intends to present and discuss data on the relationship between integrins and heparan sulfate proteoglycans in health and cancer progression. Integrins are a family of cell surface transmembrane receptors, responsible for cell-matrix and cell-cell adhesion. Integrins’ main functions include cell adhesion, migration, and survival. Heparan sulfate proteoglycans (HSPGs) are cell surface molecules that play important roles as cell receptors, cofactors, and overall direct or indirect contributors to cell organization. Both molecules can act in conjunction to modulate cell behavior and affect malignancy. In this review, we will discuss the different contexts in which various integrins, such asα5,αV,β1, andβ3, interact with HSPGs species, such as syndecans and perlecans, affecting tissue homeostasis.

scholarly journals Golgi structural defect impairs glycosaminoglycan synthesis, sulfation, and secretion

2021 ◽  
Author(s):  
Erpan Ahat ◽  
Yuefan Song ◽  
Ke Xia ◽  
Whitney Reid ◽  
Jie Li ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Chondroitin Sulfate ◽  
Structural Defect ◽  
Structural Integrity ◽  
Bifunctional Enzyme ◽  
Rna Seq ◽  
Glycosaminoglycan Synthesis ◽  
Key Enzyme ◽  
Golgi Structure ◽  
The Relationship

Synthesis of glycosaminoglycans such as heparan sulfate (HS) and chondroitin sulfate (CS) occurs in the lumen of the Golgi but the relationship between Golgi structural integrity and glycosaminoglycan synthesis is not clear. In this study, we disrupted the Golgi structure by knocking out GRASP55 and GRASP65 and determined its effect on the synthesis, sulfation, and secretion of HS and CS. We found that GRASP depletion increased HS synthesis while decreasing CS synthesis in cells, altered HS and CS sulfation, and reduced both HS and CS secretion. Using proteomics, RNA-seq and biochemical approaches, we identified EXTL3, a key enzyme in the HS synthesis pathway, whose level is upregulated in GRASP knockout cells; while GalNacT1, an essential CS synthesis enzyme, is robustly reduced. In addition, we found that GRASP depletion decreased HS sulfation via the reduction of PAPSS2, a bifunctional enzyme in HS sulfation. Our study provides the first evidence that Golgi structural defect may significantly alter the synthesis and secretion of glycosaminoglycans.

scholarly journals Golgi structural defect impairs glycosaminoglycan synthesis, sulfation, and secretion

2021 ◽  
Author(s):  
Erpan Ahat ◽  
Yuefan Song ◽  
Ke Xia ◽  
Whitney Reid ◽  
Jie Li ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Chondroitin Sulfate ◽  
Structural Defect ◽  
Structural Integrity ◽  
Bifunctional Enzyme ◽  
Rna Seq ◽  
Glycosaminoglycan Synthesis ◽  
Key Enzyme ◽  
Golgi Structure ◽  
The Relationship

Abstract Synthesis of glycosaminoglycans such as heparan sulfate (HS) and chondroitin sulfate (CS) occurs in the lumen of the Golgi but the relationship between Golgi structural integrity and glycosaminoglycan synthesis is not clear. In this study, we disrupted the Golgi structure by knocking out GRASP55 and GRASP65 and determined its effect on the synthesis, sulfation, and secretion of HS and CS. We found that GRASP depletion increased HS synthesis while decreasing CS synthesis in cells, altered HS and CS sulfation, and reduced both HS and CS secretion. Using proteomics, RNA-seq and biochemical approaches, we identified EXTL3, a key enzyme in the HS synthesis pathway, whose level is upregulated in GRASP knockout cells; while GalNacT1, an essential CS synthesis enzyme, is robustly reduced. In addition, we found that GRASP depletion decreased HS sulfation via the reduction of PAPSS2, a bifunctional enzyme in HS sulfation. Our study provides the first evidence that Golgi structural defect may significantly alter the synthesis and secretion of glycosaminoglycans.

scholarly journals SARS-CoV-2 triggers complement activation through interactions with heparan sulfate

2022 ◽  
Author(s):  
Martin W Lo ◽  
Alberto A Amarilla ◽  
John D Lee ◽  
Eduardo A Albornoz ◽  
Naphak Modhiran ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Alternative Pathway ◽  
Monocyte Activation ◽  
Surface Deposition ◽  
Factor B ◽  
The Relationship ◽  
The Complement System ◽  
Free Plasma

The complement system has been heavily implicated in severe COVID-19 with clinical studies revealing widespread gene induction, deposition, and activation. However, the mechanism by which complement is activated in this disease remains incompletely understood. Herein we examined the relationship between SARS-CoV-2 and complement by inoculating the virus in lepirudin-anticoagulated human blood. This caused progressive C5a production after 30 minutes and 24 hours, which was blocked entirely by inhibitors for factor B, C3, C5, and heparan sulfate. However, this phenomenon could not be replicated in cell-free plasma, highlighting the requirement for cell surface deposition of complement and interactions with heparan sulfate. Additional functional analysis revealed that complement-dependent granulocyte and monocyte activation was delayed. Indeed, C5aR1 internalisation and CD11b upregulation on these cells only occurred after 24 hours. Thus, SARS-CoV-2 is a non-canonical complement activator that triggers the alternative pathway through interactions with heparan sulfate.

scholarly journals Inhibition of Plasmodium falciparum Growth In Vitro and Adhesion to Chondroitin-4-Sulfate by the Heparan Sulfate Mimetic PI-88 and Other Sulfated Oligosaccharides

2006 ◽  
Vol 50 (8) ◽  
pp. 2850-2852 ◽  
Author(s):  
Yvonne Adams ◽  
Craig Freeman ◽  
Reinhard Schwartz-Albiez ◽  
Vito Ferro ◽  
Christopher R. Parish ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Phase Ii ◽  
Inhibitory Concentration ◽  
Antimalarial Activity ◽  
Placental Malaria ◽  
Sulfated Oligosaccharides ◽  
Adhesion Inhibition

ABSTRACT A panel of sulfated oligosaccharides was tested for antimalarial activity and inhibition of adhesion to the placental malaria receptor chondroitin-4-sulfate (CSA). The heparan sulfate mimetic PI-88, currently undergoing phase II anticancer trials, displayed the greatest in vitro antimalarial activity against Plasmodium falciparum (50% inhibitory concentration of 7.4 μM) and demonstrated modest adhesion inhibition to cell surface CSA.

Influence of saccharide modifications on heparin lyase III substrate specificities

Glycobiology ◽  
2021 ◽  
Author(s):  
Jiandong Wu ◽  
Pradeep Chopra ◽  
Geert-Jan Boons ◽  
Joseph Zaia
Keyword(s):  
Enzyme Activity ◽  
Structure Function ◽  
Heparan Sulfate ◽  
Chain Length ◽  
Biological Processes ◽  
Substrate Specificities ◽  
Sulfated Oligosaccharides ◽  
Flavobacterium Heparinum ◽  
Inhibited Enzyme

Abstract A library of 23 synthetic heparan sulfate (HS) oligosaccharides, varying in chain length, types, and positions of modifications, was used to analyze the substrate specificities of heparin lyase III enzymes from both Flavobacterium heparinum and Bacteroides eggerthii. The influence of specific modifications, including N-substitution, 2-O sulfation, 6-O sulfation, and 3-O sulfation on lyase III digestion was examined systematically. It was demonstrated that lyase III from both sources can completely digest oligosaccharides lacking O-sulfates. 2-O Sulfation completely blocked cleavage at the corresponding site; 6-O and 3-O sulfation on glucosamine residues inhibited enzyme activity. We also observed that there are differences in substrate specificities between the two lyase III enzymes for highly sulfated oligosaccharides. These findings will facilitate obtaining and analyzing the functional sulfated domains from large HS polymer, to better understand their structure/function relationships in biological processes.

NEW SYNTHETIC SULFATED OLIGOSACCHARIDES PROLONG SURVIVAL OF CARDIAC XENOGRAFTS BY INHIBITING RELEASE OF HEPARAN SULFATE FROM ENDOTHELIAL CELLS

1996 ◽  
Vol 61 (9) ◽  
pp. 1300-1305 ◽  
Author(s):  
Shaoping Deng ◽  
Manuel Pascual ◽  
Jinning Lou ◽  
Leo B??hler ◽  
Hans P. Wessel ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Heparan Sulfate ◽  
Sulfated Oligosaccharides

Molecular architecture of heparin and heparan sulfate: Recent developments in solution structural studies

2011 ◽  
Vol 84 (1) ◽  
pp. 65-76 ◽  
Author(s):  
Barbara Mulloy ◽  
Sanaullah Khan ◽  
Stephen J. Perkins
Keyword(s):  
Heparan Sulfate ◽  
3D Structure ◽  
Extracellular Proteins ◽  
Complex Structures ◽  
Molecular Architecture ◽  
Pyranose Ring ◽  
The Past ◽  
Recent Developments ◽  
Specific Proteins ◽  
The Relationship

The study of the relationship between the complex structures and numerous physiological functions of the glycosaminoglycans (GAGs) heparin and heparan sulfate (HS) has continued to thrive in the past decade. Though it is clear that the monosaccharide sequences of these polysaccharides must determine their ability to modulate the action of growth factors, morphogens, chemokines, cytokines, and many other extracellular proteins, the exact details of this dependence still prove elusive. Sequence determines the 3D structure of GAGs at more than one level; detailed sequences of highly sulfated regions may influence affinity for specific proteins in some cases, but in addition attention has been called to the importance of the length and spacing of these highly sulfated sequences, which are separated by unsulfated domains. Within the sulfated “S-domains”, the internal dynamics of the conformationally flexible iduronate pyranose ring have continued to interest NMR spectroscopists and molecular modelers. New studies of the relative degrees of flexibility of sulfated and unsulfated domains lead to an overall model of heparin/HS in which protein-binding, highly sulfated S-domains with well-defined conformations are separated by more flexible NA-domains.

Interstellar gas in the central region of the Galaxy

1967 ◽  
Vol 31 ◽  
pp. 239-251 ◽  
Author(s):  
F. J. Kerr
Keyword(s):  
Central Region ◽  
Galactic Plane ◽  
Neutral Hydrogen ◽  
Continuum Emission ◽  
Galactic Centre ◽  
Interstellar Gas ◽  
Hydrogen Recombination ◽  
The Galaxy ◽  
Centre Region ◽  
The Relationship

A review is given of information on the galactic-centre region obtained from recent observations of the 21-cm line from neutral hydrogen, the 18-cm group of OH lines, a hydrogen recombination line at 6 cm wavelength, and the continuum emission from ionized hydrogen.Both inward and outward motions are important in this region, in addition to rotation. Several types of observation indicate the presence of material in features inclined to the galactic plane. The relationship between the H and OH concentrations is not yet clear, but a rough picture of the central region can be proposed.

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