ProteoglycansSulphateSulfatesGlycosaminoglycanBiosynthesisSulfate proteoglycanChondroitin sulfateEndothelialSulfationKeratan sulfateAnticoagulantGlycosaminoglycansDrug heparinEpidermal growthEffective than heparinInteractsBindsEnoxaparinFibroblast growthProteinsLMWHInteractionPolysaccharideDistinctHSPGsEnzymes involvedExtracellularMolecularAffinityMoleculesSpike proteinMast cellsInhibitsSynthesisAnti-coagulantInhibitionChainsBiologicalReactivityCell surfaceWidelyBindRolesActivityConcentrationIdentificationDiscovery
Proteoglycans10
- Heparan sulfate proteoglycans (HSPGs) are present on the cell surface and in the extracellular matrix in all metazoans. (scielo.br)
- The sulfation pattern of heparan sulfate chains influences signaling events mediated by heparan sulfate proteoglycans located on the cell surface. (scielo.br)
- More specifically, these core proteins carry three to five heparan sulfate and chondroitin sulfate chains, i.e. they are proteoglycans, which allow for interaction with a large variety of ligands including fibroblast growth factors, vascular endothelial growth factor, transforming growth factor -beta, fibronectin and antithrombin -1. (leonieclaire.com)
- The liver clears triglyceride-rich lipoproteins (TRL) via LDL receptor (LDLR), LDLR-related protein-1 (LRP-1), and heparan sulfate proteoglycans (HSPGs), mostly syndecan-1. (rug.nl)
- hSulf-1 reduces the sulfation of heparan sulfate proteoglycans (HSPGs) in the extracellular matrix and inhibits binding between various cell growth factors and their receptors. (oncotarget.com)
- Heparan sulfate (HS) proteoglycans are expressed on cell surfaces and in the extracellular matrix, and take part in developmental, regenerative, as well as pathological processes. (exbio.cz)
- N-sulfated heparan sulfate proteoglycans are located in specific microdomains in the plasma membrane, independent on those formed around N-acetyl-rich heparan sulfate, and play different role in the cell signaling. (exbio.cz)
- Although it is used principally in medicine for anticoagulation, its true physiological role in the body remains unclear, because blood anti-coagulation is achieved mostly by heparan sulfate proteoglycans derived from endothelial cells. (medicalxpress.com)
- Heparin binding growth associated molecule (pleiotrophin or HBGAM), for example, interacts with the low-affinity heparan sulfate proteoglycans, which are much more abundant on endothelial cells than on smooth muscle cells or fibroblasts. (dermatologytimes.com)
- Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity. (lu.se)
Sulphate6
- Glycosaminoglycans (GAGs) comprise a class of linear, negatively charged polysaccharides composed of repeating disaccharide units of acetylated hexosamines (N-acetyl-galactosamine in the case of chondroitin sulphate and dermatan sulfate or N-acetyl-glucosamine in the case of heparin sulphate and heparin) and mainly of uronic acids (d-glucuronic acid or l-iduronic acid) being sulfated at various positions. (hindawi.com)
- hyaluronan (HA), chondroitin sulfate (CS) and dermatan sulfate (DS), heparin and heparan sulphate (HS), and keratan sulfate (KS). (hindawi.com)
- CD138 is a heparin sulphate proteoglycan that controls tumor cell survival, growth, adhesion and bone cell differentiation in MM (2). (leonieclaire.com)
- However, cells overexpressing full-length ADAMTS6 lack heparan sulphate and focal adhesions, whilst depletion of ADAMTS6 induces a prominent glycocalyx. (nos-nop.org)
- Therefore ADAMTS10 and ADAMTS6 oppositely impact heparan sulphate-rich interfaces including focal adhesions. (nos-nop.org)
- Heparins are structurally comparable to heparan sulphate. (atminhibitor.com)
Sulfates3
- The role of heparin, heparanase and heparan sulfates in hepcidin regulation. (nih.gov)
- Heparin is a special subtype of a more general class of carbohydrates, called heparan sulfates, that are produced by a wide range of cells, both in the human body, as well as in cell culture. (eurekalert.org)
- [ 4 ] Most circulating TFPI is bound to lipoproteins, but on the surface of endothelial cells, a second pool of TFPI is bound to heparan sulfates. (medscape.com)
Glycosaminoglycan3
- Kure S, Yoshie O: A syngeneic monoclonal antibody to murine Meth-A sarcoma (HepSS-1) recognizes heparan sulfate glycosaminoglycan (HS-GAG): cell density and transformation dependent alteration in cell surface HS-GAG defined by HepSS-1. (exbio.cz)
- Kure S, Yoshie O, Aso H: Metastatic potential of murine B16 melanoma correlates with reduced surface heparan sulfate glycosaminoglycan. (exbio.cz)
- Heparin (from Ancient Greek ηπαρ ( hepar ), liver), also known as unfractionated heparin , a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule. (medicalxpress.com)
Biosynthesis4
- This enzyme participates in heparan sulfate biosynthesis and glycan structures - biosynthesis 1. (wikipedia.org)
- Biosynthesis of heparin. (wikipedia.org)
- In particular, the researchers found a critical gene in heparin biosynthesis: ZNF263 (zinc-finger protein 263). (eurekalert.org)
- The researchers report that ZNF263 appears to be an active repressor of heparin biosynthesis throughout most cell types, and mast cells are enabled to produce heparin because ZNF263 is suppressed in these cells. (eurekalert.org)
Sulfate proteoglycan4
- His longstanding research interest has been the role of the extracellular matrix in nervous system development, especially the function of the heparan sulfate proteoglycan agrin. (nccu.edu)
- Retina development in zebrafish requires the heparan sulfate proteoglycan agrin. (nccu.edu)
- It can reduce the sulfation of cell surface heparan sulfate proteoglycan (HSPG) and inhibit various growth factor receptor-mediated signaling pathways. (oncotarget.com)
- I n this highly cited paper , we identify heparan sulfate proteoglycan as a novel receptor and potential target for inhibition of exosome mediated glioma tumor development. (lu.se)
Chondroitin sulfate1
- The technology can be applied to prepare oligosaccharides belonging to the heparin-, heparan sulfate-, chondroitin sulfate-, keratan sulfate- or hyaluronic acid- class of GAGs. (selectbiosciences.com)
Endothelial5
- In this chapter, we will review some of the current and most promising strategies that have been used over the years to develop polymeric materials with improved hemocompatibility, including highly hydrophilic or hydrophobic surfaces, albumin coated surfaces, zwitterionic polymers, attached endothelial cells, patterned surfaces, immobilized heparin, and nitric oxide (NO) releasing/generating surfaces. (springer.com)
- Syndecans are thought to function predominantly as coreceptors for other receptors such as integrins, members of the fibroblast growth factor family, vascular endothelial cell growth factor, and transforming growth factor β, which need heparin sulfate for signaling. (leonieclaire.com)
- Heparin and HS have been associated with cell-biological processes, cell adhesion and regulation of enzymatic catalysis while HS chains have been shown to interact with a variety of growth factors (fibroblast growth factors and vascular endothelial growth factor), chemokines, ECM proteins, enzymes, and antithrombin. (caslab.com)
- When heparin is administered, the endothelial cell-bound TFPI is released and the plasma level rises severalfold. (medscape.com)
- Hypoxia triggers a proangiogenic pathway involving cancer cell microvesicles and PAR-2-mediated heparin-binding EGF signaling in endothelial cells. (lu.se)
Sulfation6
- Higher degrees of sulfation and iduronic acid content in the polysaccharide chain confers the name heparin rather than heparan sulfate to the chain. (reactome.org)
- This enzyme is a type II integral membrane protein and is responsible for 6-O-sulfation of heparan sulfate. (nih.gov)
- Heparan sulfate (HS) is a linear polysaccharide composed of 50-200 glucosamine and uronic acid (glucuronic acid or iduronic acid) disaccharide repeats with epimerization and various sulfation modifications. (leonieclaire.com)
- The UB research has focused on key enzymes involved in the regulation of heparan sulfation, which plays a key role in signaling between cells. (buffalo.edu)
- The heparanome, Sim explained, refers to the highly complex nature of how heparin sulfate, a carbohydrate polymer that is modified by sulfation in a very specific way, appears on the surface of a cell. (buffalo.edu)
- In the Nature Communications paper, Sim and his colleagues show that SULF2, one of the enzymes involved in regulating heparan sulfation, is highly expressed by OPCs. (buffalo.edu)
Keratan sulfate1
- [ 1 ] The resulting incomplete degradation process leads to abnormal accumulation of heparan sulfate, dermatan sulfate, and keratan sulfate, and the abnormal accumulation of these compounds interferes with cell function. (medscape.com)
Anticoagulant3
- Heparin, low molecular weight heparins (LMWH) and ultra-low molecular weight heparins (ULMWH) are widely used as anticoagulant drugs and they have been shown to regulate cellular process by binding, stabilizing and activating various growth factors. (caslab.com)
- This includes the use of the anticoagulant heparin, which possesses extraordinary binding to the SARS-CoV-2 spike protein, and heparin/heparan sulfate analogs and other functional polysaccharides that possess exceptional binding without anticoagulation. (aiche.org)
- Heparin has long been used as a blood thinner, or anticoagulant, for patients with blood clotting disorders or after surgery to prevent complications. (medicalxpress.com)
Glycosaminoglycans4
- In virtually all animal tissues, the cell membranes and the extracellular matrices (ECM) are decorated with glycosaminoglycans (GAGs) such as heparin and heparan sulfate (HS), which are linear sulfated polysaccharides. (caslab.com)
- Mammalian glycosaminoglycans (GAGs) are sulfated polysaccharides commonly exemplified by their most abundant forms: heparin, heparan sulfate (HS) and chondroitin/dermatan sulfate (CS/DS). (ku.dk)
- Heparin and other glycosaminoglycans have profound activity in vitro on the regulation of complement activity. (rpi.edu)
- Unless it is complexed to TF in the presence of heparin or cell surface glycosaminoglycans, factor VIIa resists being inhibited by antithrombin. (medscape.com)
Drug heparin1
Epidermal growth1
- Ovarian cancer cell heparan sulfate 6-O-sulfotransferases regulate an angiogenic program induced by heparin-binding epidermal growth factor (EGF)-like growth factor/EGF receptor signaling. (nih.gov)
Effective than heparin1
Interacts2
- Hence, although surface plasmon resonance shows that heparin binds to C1INH, heparin augmentation of C1INH activity appears to require a terniary complex in which cell bound C1 interacts with both heparin and C1INH. (rpi.edu)
- We show that SARS-CoV-2 spike protein interacts with both cellular heparan sulfate and angiotensin converting enzyme 2 (ACE2) through its Receptor Binding Domain (RBD). (cdc.gov)
Binds2
- Lipscombe RJ, Nakhoul AM, Sanderson CJ, Coombe DR: Interleukin-5 binds to heparin/heparan sulfate. (exbio.cz)
- Using Bio-Layer Interferometry on the Octet ® platform, Dr. Lopez-Munoz found that N binds specifically to heparan sulfate/heparin with high affinity, but also binds to a set of 11 human chemokines, inhibiting chemotaxis. (sartorius.com)
Enoxaparin1
- Agents derived from the use of heparin include enoxaparin, dalteparin, tinzaparin and fondaparinux. (selectbiosciences.com)
Fibroblast growth2
- These studies are currently focusing on elucidating the mechanisms by which agrin modulates the function of heparin-binding growth factors and morphogens, such as fibroblast growth factors (Fgfs) and sonic hedgehog (Shh), during zebrafish nervous system development. (nccu.edu)
- From 2011-2015, I studied the specificity of interactions of fibroblast growth factors (FGF) and heparan sulfate (HS) during my PhD in University of Liverpool. (liverpool.ac.uk)
Proteins2
- Syndecans are transmembrane proteins with an N-terminal signal sequence and an ectodomain-containing consensus sequences for heparin-binding extracellular ligands including growth factors, extracellular matrix proteins, cell adhesion molecules, among others. (leonieclaire.com)
- My work focuses on the identification and quantification of heparin-binding proteins in the pericellular matrix of cells and tissues in Alzhiemer's disease. (liverpool.ac.uk)
LMWH2
- Low molecular weight heparin (LMWH), the guideline based drug for prophylaxis and treatment of cancer-associated thrombosis, was recently shown to sensitize cisplatin resistant A2780cis human ovarian cancer cells for cisplatin cytotoxicity upon 24 h pretreatment with 50 μg × mL -1 of the LMWH tinzaparin in vitro , equivalent to a therapeutic dosage. (oncotarget.com)
- According to clinical guidelines for antithrombotic prophylaxis or treatment of patients in oncology, low molecular weight heparin (LMWH) is the drug of choice [ 2 ]. (oncotarget.com)
Interaction4
- This study will further promote our understanding of the interaction of heparin sulfate with Cryptosporidium and the mechanism of Cryptosporidium infection, and will facilitate the development of anti-cryptosporidial agents," says Associate Professor Kato. (sciencedaily.com)
- We also show that the binding site for the C-terminal region spans multiple domains and overlaps with a heparin interaction site. (eurekamag.com)
- The interaction of heparin and heparan sulfate with C1INH was first examined using surface plasmon resonance. (rpi.edu)
- No interaction between C1INH and heparan sulfate could be observed. (rpi.edu)
Polysaccharide2
- Researchers have demonstrated that heparin, a type of sulfated polysaccharide, inhibits infection with Cryptosporidium parvum, a protozoan that causes diarrhea in humans and other mammals. (sciencedaily.com)
- In addition, the group investigated the mechanism of infection by the Cryptosporidium parasite, and elucidated that heparan sulfate, a sulfated polysaccharide found on the surface of mammalian cells, is involved in Cryptosporidium infection. (sciencedaily.com)
Distinct3
- Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biological activities. (nih.gov)
- Heparin is distinct from HS in that it is produced primarily by mast cells, whereas, HS is produced by all cell types. (leonieclaire.com)
- Chung JS, Shiue LH, Duvic M, Pandya A, Cruz PD Jr, Ariizumi K: Sézary syndrome cells overexpress syndecan-4 bearing distinct heparan sulfate moieties that suppress T-cell activation by binding DC-HIL and trapping TGF-beta on the cell surface. (exbio.cz)
HSPGs1
- HSPGs interact with growth factors and receptors through heparan sulfate (HS) chains. (scielo.br)
Enzymes involved1
- Since regulators for heparin were not known, a research team led by UC San Diego professors Jeffrey Esko and Nathan Lewis used bioinformatic software to scan the genes encoding enzymes involved in heparin production and specifically look for sequence elements that could represent binding sites for transcription factors. (eurekalert.org)
Extracellular2
- Heparan sulfate (HS) is a component of the extracellular matrix. (leonieclaire.com)
- The mouse monoclonal antibody HepSS-1 (also known as HepSS1) recognizes N-sulfated heparan sulfate (extracellular antigen) present in many species. (exbio.cz)
Molecular2
Affinity1
- I study the heparin interactome of AD monocyte derived macrophages using established affinity proteomics pipeline, where cell fractions are isolated by centrifugation and subjected to heparin/3S-HS affinity chromatography. (liverpool.ac.uk)
Molecules2
- Additionally, heparin and HS molecules were found to mediate the viral adhesion and the infection process and considered as important factors in the host-pathogen interactions. (caslab.com)
- Although the mechanisms of action of these reagents remain to be clarified, several lines of evidence connect most of the anti-prion agents with molecules of the heparin family. (europa.eu)
Mast cells5
- Yet, heparin is exclusively produced in a special type of blood cells called mast cells. (eurekalert.org)
- Researchers at UC San Diego reasoned that heparin synthesis must be under the control of certain gene regulators (called transcription factors), whose tissue-specific occurrence might give mast cells the unique ability to produce heparin. (eurekalert.org)
- Interestingly, analysis of gene expression data from human white blood cells showed suppression of ZNF263 in mast cells (which produce heparin in vivo) and basophils, which are related to mast cells. (eurekalert.org)
- Cell lines used in industry (such as CHO cells that normally are unable to produce heparin) could be genetically modified to inactivate ZNF263 which could enable them to produce heparin, like mast cells do. (eurekalert.org)
- Heparin is usually stored within the secretory granules of mast cells and released only into the vasculature at sites of tissue injury. (medicalxpress.com)
Inhibits1
- The group showed for the first time that heparin inhibits the infection of Cryptosporidium , and that the greater the concentration of heparin the greater the inhibitory effect. (sciencedaily.com)
Synthesis2
- The work in PNAS provides new insights on exactly how cells control synthesis of heparin. (eurekalert.org)
- While some research has been done on this gene regulator, this is the first major regulator involved in heparin synthesis," said Lewis. (eurekalert.org)
Anti-coagulant1
- Heparin is a potent anti-coagulant and the most prescribed drug in hospitals, yet cell-culture-based production of heparin is currently not possible. (eurekalert.org)
Inhibition1
Chains1
- SULF1 and SULF2 are two endo-sulfatases that can cleave specific 6-O-sulfate groups within the heparan chains. (scielo.br)
Biological1
Reactivity1
- They found that the heparan sulfate that this cell line would normally produce was now chemically altered and showed a reactivity that was closer to heparin. (eurekalert.org)
Cell surface1
- These data suggest that heparan sulfate may sequester fibrillin at the cell surface via FUN-EGF3 prior to aggregation of the C terminus, thereby regulating microfibril assembly. (eurekamag.com)
Widely1
- Heparin, a widely available and affordable drug, has found to limit lung damage when inhaled by COVID-19 patients. (medicalxpress.com)
Bind1
- induce focal adhesions, bind heparin and syndecan-4. (nos-nop.org)
Roles1
- Mii Y, Yamamoto T, Takada R, Mizumoto S, Matsuyama M, Yamada S, Takada S, Taira M: Roles of two types of heparan sulfate clusters in Wnt distribution and signaling in Xenopus. (exbio.cz)
Activity4
- The studies reported here examined the mechanism whereby heparin enhances C1 esterase inhibitor (C1INH) activity on C1 esterase (C1). (rpi.edu)
- When C1 was in the fluid phase, both heparin and LMW heparin were relatively ineffective at augmenting C1INH activity on C1. (rpi.edu)
- This is the first report of LMW heparin augmenting C1INH activity. (rpi.edu)
- Heparan sulfate neither interacted with C1INH nor did it augment C1INH activity. (rpi.edu)
Concentration1
- Separation of EA.hy926 cells (red-filled) from EA.hy926 cells treated with heparinase (1 hour, 1 UI per ml of cell suspension) stained using anti-N-sulfated heparan sulfate (HepSS-1) PE antibody (concentration in sample 10 μg/ml). (exbio.cz)
Identification1
Discovery1
- The researchers believe this gene regulator is a key discovery on the way to industrial heparin production. (eurekalert.org)