Development of the retinal vascular network is strictly confined within the neuronal retina, allowing the intraocular media to be optically transparent. However, in retinal ischemia, pro-angiogenic factors (including vascular endothelial growth factor-A, VEGF-A) induce aberrant guidance of retinal vessels into the vitreous. Here, we show that the soluble ...
PubMed Central
VEGF was first described as vascular permeability factor, a potent inducer of vascular leakage. Genetic evidence indicates that VEGF-stimulated endothelial proliferation in vitro and angiogenesis in vivo depend on heparan sulfate, but a requirement for heparan sulfate in vascular hyperpermeability has not been ...
PubMed
Six genes involved in the heparan sulfate and heparin metabolism pathway, DSEL (dermatan sulfate epimerase-like), EXTL1 (exostoses (multiple)-like 1), HS6ST1 (heparan sulfate 6-O-sulfotransferase 1), HS6ST3 (heparan sulfate 6-O-sulfotransferase 3), ...
Technology Transfer Automated Retrieval System (TEKTRAN)
Heparan sulfate of the cell surface of cultured Chinese hamster cells (line CHO) was promptly released when the cells were incubated with balanced salt solutions containg heparin. The released heparan sulfate included multichain proteoglycan of high molecular weight. The data suggest that the cell-surface ...
Energy Citations Database
Herpes simplex virus type-1 (HSV-1) is one of many pathogens that use the cell surface glycosaminoglycan heparan sulfate as a receptor. Heparan sulfate is highly expressed on the surface and extracellular matrix of virtually all cell types making it an ideal receptor. Heparan ...
A difference in the extent of sulfation between the heparan sulfate isolated from Swiss 3T3 mouse cells and that from Swiss 3T3 cells transformed by the DNA virus SV40 has been reported previously. This variance is manifested by different chromatographic and electrophoretic properties. Heparan ...
Metabolic and structural characteristics of cellular heparan sulfate are used to formulate guidelines for the possible functional roles of the N-sulfated glycosaminoglycans.
DOE Information Bridge
... CODING, SIGNALS, GENES, BEHAVIOR, SULFATES, MICE, IN VIVO ANALYSIS, CELLS(BIOLOGY), MOLECULAR PROPERTIES, GENETICS ...
DTIC Science & Technology
Heparan sulfate and heparin are highly sulfated polysaccharides exhibiting essential physiological functions. The sulfation patterns determine the functional selectivity for heparan sulfate and heparin. Chemical synthesis of heparan ...
Heparan sulfate proteoglycans (HSPGs), strategically located at the cell-tissue-organ interface, regulate major biological processes, including cell proliferation, migration, and adhesion. These vital functions are compromised in tumors, due, in part, to alterations in heparan sulfate (HS) expression and structure. ...
The authors have isolated Chinese hamster ovary cell mutants defective in proteoglycan synthesis by radiographic screening for cells unable to incorporate TVSO4 into acid-precipitable material. Some mutants did not incorporate TVSO4 into acid-precipitable material, whereas others incorporated about 3-fold less radioactivity. HPLC anion exchange chromatographic analysis of radiolabelled ...
Heparan sulfate is a highly sulfated polysaccharide that exhibits important physiological and pathological functions. The glucosamine residue of heparan sulfate can carry sulfo groups at the 2-N, 3-O, and 6-O positions, leading to diverse polysaccharide structures. ...
... Title : The Role(s) of Heparan Sulfate Proteoglycan(s) in the wnt-1 Signaling Pathway. Descriptive Note : Final rept. ... Personal Author(s) : Lin, Xinhua. ...
... Title : The Role(s) of Heparan Sulfate Proteoglycan(s) in the wnt-1 Signaling Pathway. ... Personal Author(s) : Lin, Xinhua. Handle / proxy Url : ...
Heparan sulfate (HS) binds growth factors, protein-degrading enzymes, and other bioactive proteins, and to regulate their activities. Many of these proteins have strong implications in human breast cancer. There is also evidence that cellular HS productio...
National Technical Information Service (NTIS)
... 10.1095/biolreprod66.1.144 Coordinate Expression of Anticoagulant Heparan Sulfate Proteoglycans and Serine Protease Inhibitors i...
NBII National Biological Information Infrastructure
Heparan sulfate has been shown to be an important mediator of Plasmodium sporozoite homing and invasion of the liver, but the role of this glycosaminoglycan in mosquito vector host-sporozoite interactions is unknown. We have biochemically characterized the function of Anopheles gambiae peptide-O-xylosyltransferase (AgOXT1) and confirmed that AgOXT1 can ...
SynopsisHeparan sulfate has been shown to be an important mediator of Plasmodium sporozoite homing and invasion of the liver, but the role of this glycosaminoglycan in mosquito vector host-sporozoite interactions is unknown. We have biochemically characterized the function of Anopheles gambiae peptide-O-xylosyltransferase (AgOXT1) and confirmed that AgOXT1 ...
Diabetes -associated hyperlipidemia is generally attributed to reduced clearance of plasma lipoproteins, especially remnant lipoproteins enriched in cholesterol and triglycerides. Hepatic clearance of remnants occurs via low density lipoprotein receptors and the heparan sulfate proteoglycan, syndecan-1. Previous studies have suggested alterations in ...
... and specifically interact with heparin, heparan sulfate ... activating and FGF2 antagonist type I ... peptidomimetics, growth factor antagonists, apoptosis ...
A sensitive and accurate quantitative assay for the measurement of minor amounts of chondroitin/dermatan sulfate and heparan sulfate that does not require specific apparatus or reagents is described. The assay involves labeling of chondroitin sulfate A following reaction of carboxyl groups with biotin hydrazide in ...
Glycosaminoglycans synthesized by human skin fibroblasts were simultaneously radiolabelled with D-[1-(3H)]glucosamine and Na2(35)SO4. Considering 3H incorporation, we found that IFNgamma increased the production of glycosaminoglycan synthesis, including hyaluronic acid, heparan and chondroitin/dermatan sulfate. In contrast, the production of ...
Sulfation is an important biological process that modulates the function of numerous molecules. It is directly mediated by cytosolic and Golgi sulfotransferases, which use 3?-phosphoadenosine 5?-phosphosulfate to produce sulfated acceptors and 3?-phosphoadenosine 5?-phosphate (PAP). Here, we identify a Golgi-resident PAP 3?-phosphatase (gPAPP) and ...
Heparan sulfate proteoglycans (HSPGs) regulate a number of major developmental processes, but their roles in synovial joint formation remain unknown. Here we created conditional mouse embryo mutants lacking Ext1 in developing joints by mating Ext1(f/f) and Gdf5-Cre mice. Ext1 encodes a subunit of the Ext1/Ext2 Golgi-associated protein complex responsible ...
Selenate, a sulfation inhibitor, blocks the synthesis of heparan sulfate and chondroitin sulfate by cultured endothelial cells. In contrast, selenate does not affect the production of hyaluronic acid, a nonsulfated glycosaminoglycan. No differences in molecular weight, ({sup 3}H)glucosamine/({sup 35}S)sulfuric acid ...
... sulfate chains, there was no difference in staining (data ... Indeed, differences in MDA-MB-231 cell surface ... 1 inhibits cell invasion into type I collagen. ...
... by the fact that mutations of Ext1, the gene ... CELLS(BIOLOGY), GENETICS, MAMMARY GLANDS, DISSECTION, GROWTH(GENERAL), SULFATES. ...
Heparan sulfate proteoglycans (HSPGs) play vital roles in every step of tumor progression allowing cancer cells to proliferate, escape from immune response, invade neighboring tissues, and metastasize to distal sites away from the primary site. Several cancers including breast, lung, brain, pancreatic, skin, and colorectal cancers show ...
Although interleukin-2 (IL-2) is typically considered a soluble cytokine, our laboratory has shown that the availability of IL-2 in lymphoid tissues is regulated, in part, by an association with heparan sulfate glycosaminoglycan. Heparan sulfate is usually found in proteoglycan form, in which the ...
Over the past decade, the glycosaminoglycans heparin and heparan sulfate have been shown to bind and regulate the activities of many proteins. Established techniques have provided both qualitative and quantitative information regarding these interactions, leading to a general view that proteins bind with a variety of affinities to particular sequences ...
The structure of the glycosaminoglycan chain of a heparan sulfate proteoglycan isolated from the conditioned medium of an endothelial cell line has been analyzed by using various degradative enzymes (heparitinase I, heparitinase II, heparinase, glycuronidase, sulfatases) from Flavobacterium heparinum. (/sup 35/S)sulfuric acid and/or (/sup 3/H) glucosamine ...
The development and antigen-dependent differentiation of B lymphocytes are orchestrated by an array of growth factors, cytokines, and chemokines that require tight spatiotemporal regulation. Heparan sulfate proteoglycans specifically bind and regulate the bioavailability of soluble protein ligands, but their role in the immune system has remained largely ...
Skin fibroblasts from two patients who had symptoms of the Sanfilippo syndrome (mucopolysaccharidosis III) accumulated excessive amounts of heparan sulfate and were unable to release sulfate from N-acetylglucosamine-6-sulfate linkages in heparan sulfate-derived ...
Heparan sulfate chains are initially synthesized on core proteins as linear polysaccharides composed of glucuronic acid-N-acetylglucosamine repeating units and subjected to marked structural modification by sulfation at various places and epimerization of hexuronic acid residues (C5-epimerase) at the Golgi lumen and further by ...
Cell surface glycosaminoglycans (GAGs) play an important role in the attachment and invasion process of a variety of intracellular pathogens. We have previously demonstrated that heparan sulfate proteoglycans (HSPG) mediate the invasion of trypomastigote forms of Trypanosoma cruzi in cardiomyocytes. Herein, we analysed whether GAGs are also implicated in ...
Heparan sulfate (HS), due to its ability to interact with a multitude of HS-binding factors, is involved in a variety of physiological and pathological processes. Remarkably diverse fine structure of HS, shaped by non-exhaustive enzymatic modifications, influences the interaction of HS with its partners. Here we characterized the HS profile of normal human ...
... 1994. In situ hybridization. In Drosophila melanogaster: Practical Uses in ... In Drosophila melanogaster: Practical Uses in Cell and Molecular ...
... activities of this gene, mutant embryos develop with segment polarity phenotypes reminiscent to loss of either Wingless (Wg) or Hedgehog signaling ...
... activity of the intact protein and specifically interact with heparin, heparan sulfate ... The role of the TGFbeta-activating and FGF2 antagonist type I ...
... activity of the intact protein and specifically interact with heparin, heparan sulfate ... The role of the TGFBeta-activating and FGF2 antagonist type I ...
... domestic fowl. It was originally isolated in the 1930s and continues to cause ... tropism in cell culture. In order to understand the acquired tropism of ... ...
... Treatment with purified syndecan-1 produces strong growth suppression in multiple myeloma cell lines, a poorly differentiated squamous cell ...
... we examined the development of FSP1-Cre;Ext1flox/flox mice. We found that these mutant mice grow normally without any gross abnormalities and ...
... This project will conduct cohort study using genetic mouse models to ... We have also characterized the gene recombination pattern induced by the ...
Hemodynamic stress is a critical factor in the onset of atherosclerosis such that reduced rates of shear stress occurring at regions of high curvature are more prone to disease. The level of shear stress has direct influence on the thickness and integrity of the glycocalyx layer. Here we show that heparan sulfate, the main component of the glycocalyx ...
Fibroblast growth factors (FGFs) play multiple roles during development and in adult tissues as paracrine regulators of growth and differentiation. FGFs signal through transmembrane receptor tyrosine kinases, but heparan sulfate is also required for signaling by members of the FGF family. In addition, heparan ...
... of the coronary arterial wall, Brigham & ... 2008 Drug Transport in Artery Walls, FDA/NSF/NIH ... Vascular cell-derived heparan sulfate shows coupled ...
Center for Biologics Evaluation and Research (CBER)
Heparan sulfate has been isolated for the first time from the mosquito Anopheles stephensi, a known vector for Plasmodium parasites, the causative agents of malaria. Chondroitin sulfate, but not dermatan sulfate or hyaluronan, was also present in the mosquito. The glycosaminoglycans were isolated, from salivary ...
We have revealed that in Caenorhabditis elegans, non-sulfated chondroitin is required for normal cell division and cytokinesis at an early developmental stage, whereas heparan sulfate is essential for embryonic morphogenesis in the later stages of development. To clarify the roles of chondroitin sulfate and ...
The tumor suppressor genes EXT1 and EXT2 are involved in the formation of multiple osteochondromas, which can progress to become secondary peripheral chondrosarcomas. The most common chondrosarcoma subtype is primary central chondrosarcoma, which occurs in the medullar cavity of bone. The EXT1/EXT2 protein complex is involved in heparan sulfate ...
A difference in the expression and metabolism of (/sup 35/S)sulfated glycosaminoglycans between rat mammary tumor cells derived from a primary tumor and those from its metastatic lesions has been observed. Cells from the primary tumor possessed about equal quantities of chondroitin sulfate and heparan sulfate on ...
Metabolically /sup 35/S- or /sup 3/H-labeled heparan sulfate was isolated from murine Reichert's membrane, an extraembryonic basement membrane produced by parietal endoderm cells, and from the basement membrane-producing Engelbreth-Holm-Swarm mouse tumor. The polysaccharides were subjected to structural analysis involving identification of ...
After transport in the blood and implantation in the microcirculation, metastatic tumor cells must invade the vascular endothelium and underlying basal lamina. Mouse B16 melanoma sublines were used to determine the relation between metastatic properties and the ability of the sublines to degrade enzymatically the sulfated glycosaminoglycans present in the extracellular matrix ...
NASA Astrophysics Data System (ADS)
BackgroundLymph node metastasis constitutes a key event in tumor progression. The molecular control of this process is poorly understood. Heparan sulfate is a linear polysaccharide consisting of unique sulfate-modified disaccharide repeats that allow the glycan to bind a variety of proteins, including chemokines. While some chemokines ...
The biosynthesis of heparan sulfate (HS) involves an array of specialized sulfotransferases. Here, we present a study aimed at engineering the substrate specificity of different HS 3-O-sulfotransferase isoforms. Based on the crystal structures, we identified a pair of amino acid residues responsible for selecting the substrates. Mutations of these residues ...
