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Heparan sulfate

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https://www.readbyqxmd.com/read/27924424/rgta-%C3%A2-or-regenerating-agents-mimic-heparan-sulfate-in-regenerative-medicine-from-concept-to-curing-patients
#1
REVIEW
Denis Barritault, Marie Gilbert-Sirieix, Kim Lee Rice, Fernando Siñeriz, Dulce Papy-Garcia, Christophe Baudouin, Pascal Desgranges, Gilbert Zakine, Jean-Louis Saffar, Johan van Neck
The importance of extracellular matrix (ECM) integrity in maintaining normal tissue function is highlighted by numerous pathologies and situations of acute and chronic injury associated with dysregulation or destruction of ECM components. Heparan sulfate (HS) is a key component of the ECM, where it fulfils important functions associated with tissue homeostasis. Its degradation following tissue injury disrupts this delicate equilibrium and may impair the wound healing process. ReGeneraTing Agents (RGTA(®)s) are polysaccharides specifically designed to replace degraded HS in injured tissues...
December 7, 2016: Glycoconjugate Journal
https://www.readbyqxmd.com/read/27920806/hereditary-multiple-exostoses-a-review-of-clinical-appearance-and-metabolic-pattern
#2
REVIEW
Giovanni Beltrami, Gabriele Ristori, Guido Scoccianti, Angela Tamburini, Rodolfo Capanna
Hereditary multiple exostoses (HME) is an inherited genetic condition characterized by the presence of multiple exostoses (osteochondromas). MHE is a relatively rare autosomal dominant disorder, mainly caused by loss of function mutations in two genes: exostosin-1 (EXT1) and exostosin-2 (EXT2). These genes are linked to heparan sulfate (HS) synthesis, but the specific molecular mechanism leading to the disruption of the cartilage structure and the consequent exostoses formation is still not resolved. The aim of this paper is to encounter the main aspects of HME reviewing the literature, in order to improve clinical features and evolution, and the metabolic-pathogenetic mechanisms underlying...
May 2016: Clinical Cases in Mineral and Bone Metabolism
https://www.readbyqxmd.com/read/27912844/heparanase-from-basic-research-to-therapeutic-applications-in-cancer-and-inflammation
#3
Israel Vlodavsky, Preeti Singh, Ilanit Boyango, Lilach Gutter-Kapon, Michael Elkin, Ralph D Sanderson, Neta Ilan
Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Heparanase expression is enhanced in almost all cancers examined including various carcinomas, sarcomas and hematological malignancies. Numerous clinical association studies have consistently demonstrated that upregulation of heparanase expression correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. In contrast, knockdown of heparanase or treatments of tumor-bearing mice with heparanase-inhibiting compounds, markedly attenuate tumor progression further underscoring the potential of anti-heparanase therapy for multiple types of cancer...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27910891/elevated-cerebral-spinal-fluid-biomarkers-in-children-with-mucopolysaccharidosis-i-h
#4
Gerald V Raymond, Marzia Pasquali, Lynda E Polgreen, Patricia I Dickson, Weston P Miller, Paul J Orchard, Troy C Lund
Mucopolysaccharidosis (MPS) type-IH is a lysosomal storage disease that results from mutations in the IDUA gene causing the accumulation of glycosaminoglycans (GAGs). Historically, children with the severe phenotype, MPS-IH (Hurler syndrome) develop progressive neurodegeneration with death in the first decade due to cardio-pulmonary complications. New data suggest that inflammation may play a role in MPS pathophysiology. To date there is almost no information on the pathophysiologic changes within the cerebral spinal fluid (CSF) of these patients...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900575/glycosaminoglycanomics-where-we-are
#5
Sylvie Ricard-Blum, Frédérique Lisacek
Glycosaminoglycans regulate numerous physiopathological processes such as development, angiogenesis, innate immunity, cancer and neurodegenerative diseases. Cell surface GAGs are involved in cell-cell and cell-matrix interactions, cell adhesion and signaling, and host-pathogen interactions. GAGs contribute to the assembly of the extracellular matrix and heparan sulfate chains are able to sequester growth factors in the ECM. Their biological activities are regulated by their interactions with proteins. The structural heterogeneity of GAGs, mostly due to chemical modifications occurring during and after their synthesis, makes the development of analytical techniques for their profiling in cells, tissues, and biological fluids, and of computational tools for mining GAG-protein interaction data very challenging...
November 30, 2016: Glycoconjugate Journal
https://www.readbyqxmd.com/read/27899064/gdf5-mediated-enhancement-of-chondrocyte-phenotype-is-inhibited-by-heparin-implication-for-the-use-of-heparin-in-the-clinic-and-in-tissue-engineering-applications
#6
Bethanie Imogen Ayerst, Raymond A A Smith, Victor Nurcombe, Anthony J Day, Catherine L R Merry, Simon Cool
The highly sulfated glycosaminoglycan (GAG) heparin is widely used in the clinic as an anticoagulant, and researchers are now using it to enhance stem cell expansion/ differentiation protocols, as well as to improve the delivery of growth factors for tissue engineering strategies. Growth differentiation factor 5 (GDF5) belongs to the bone morphogenetic protein family of proteins and is vital for skeletal formation, however, its interaction with heparin and heparan sulfate (HS) has not been studied. We identify GDF5 as a novel heparin/ HS-binding protein, and show that HS proteoglycans are vital in localizing GDF5 to the cell surface...
November 29, 2016: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/27898729/rna-contaminates-glycosaminoglycans-extracted-from-cells-and-tissues
#7
Jasper J van Gemst, Markus A Loeven, Mark J J de Graaf, Jo H M Berden, Ton J Rabelink, Cornelis H Smit, Johan van der Vlag
Glycosaminoglycans (GAGs) are linear negatively charged polysaccharides and important components of extracellular matrices and cell surface glycan layers such as the endothelial glycocalyx. The GAG family includes sulfated heparin, heparan sulfate (HS), dermatan sulfate (DS), chondroitin sulfate (CS), keratan sulfate, and non-sulfated hyaluronan. Because relative expression of GAGs is dependent on cell-type and niche, isolating GAGs from cell cultures and tissues may provide insight into cell- and tissue-specific GAG structure and functions...
2016: PloS One
https://www.readbyqxmd.com/read/27892652/aliphatic-polyethers-with-sulfate-carboxylate-and-hydroxyl-side-groups-do-they-show-anticoagulant-properties
#8
Jagadeesh Malineni, Smriti Singh, Sabine Tillmann, Helmut Keul, Martin Möller
There is increasing interest in the synthesis of low molecular weight heparin and heparan sulfate mimetic polymers because of their various potential biomedical applications. The functional activity of heparin and heparan sulfate is believed to arise from the presence of a number of functional groups, such as hydroxyl, carboxylate and sulfate groups. The design and synthesis of novel heparin-mimetic polymers with a particular functionality poses a formidable challenge and requires carefully control of the selective conversion of functional groups on the polymer chain...
November 28, 2016: Macromolecular Bioscience
https://www.readbyqxmd.com/read/27890389/heparanase-confers-a-growth-advantage-to-differentiating-murine-embryonic-stem-cells-and-enhances-oligodendrocyte-formation
#9
Anqi Xiong, Soumi Kundu, Maud Forsberg, Yuyuan Xiong, Tobias Bergström, Tanja Paavilainen, Lena Kjellén, Jin-Ping Li, Karin Forsberg-Nilsson
Heparan sulfate proteoglycans (HSPGs), ubiquitous components of mammalian cells, play important roles in development and homeostasis. These molecules are located primarily on the cell surface and in the pericellular matrix, where they interact with a multitude of macromolecules, including many growth factors. Manipulation of the enzymes involved in biosynthesis and modification of HSPG structures alters the properties of stem cells. Here, we focus on the involvement of heparanase (HPSE), the sole endo-glucuronidase capable of cleaving of HS, in differentiation of embryonic stem cells into the cells of the neural lineage...
November 23, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27888308/comparative-analysis-of-inlight%C3%A2-labeled-enzymatically-depolymerized-heparin-by-reverse-phase-chromatography-and-high-performance-mass-spectrometry
#10
John B Mangrum, Akul Y Mehta, Alhumaidi B Alabbas, Umesh R Desai, Adam M Hawkridge
Structural characterization of the microheterogeneity of heparin, heparan sulfate, and other glycosaminoglycans is a major analytical challenge. We present the use of a stable isotope-labeled hydrazide tag (INLIGHT™) with high-resolution/accurate mass (HRAM) reverse-phase LC-MS/MS, which was recently introduced for detailed study of N-glycan heterogeneity, to characterize heparinase-digested heparin (digHep) products without the use of semi-volatile ion pairing reagents. Using both full scan LC-MS and data-dependent LC-MS/MS, we identified 116 unique digHep species, a feat possible because of INLIGHT™ labeling...
November 25, 2016: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/27888216/drosophila-sulf1-is-required-for-the-termination-of-intestinal-stem-cell-division-during-regeneration
#11
Masahiko Takemura, Hiroshi Nakato
Stem cell division is activated to trigger regeneration in response to tissue damage. The molecular mechanisms by which this stem cell mitotic activity is properly repressed at the end of regeneration are poorly understood. Here we show that a specific modification of heparan sulfate (HS) is critical in regulating Drosophila intestinal stem cell (ISC) division during normal midgut homeostasis and regeneration. Loss of the extracellular HS endosulfatase Sulf1 results in increased ISC division during normal homeostasis, which is caused by upregulation of mitogenic signaling including the JAK/STAT, EGFR, and Hedgehog pathways...
November 25, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27886097/investigating-glycol-split-heparin-derived-inhibitors-of-heparanase-a-study-of-synthetic-trisaccharides
#12
Minghong Ni, Stefano Elli, Annamaria Naggi, Marco Guerrini, Giangiacomo Torri, Maurice Petitou
Heparanase is the only known endoglycosidase able to cleave heparan sulfate. Roneparstat and necuparanib, heparanase inhibitors obtained from heparin and currently being tested in man as a potential drugs against cancer, contain in their structure glycol-split uronic acid moieties probably responsible for their strong inhibitory activity. We describe here the total chemical synthesis of the trisaccharide GlcNS6S-GlcA-1,6anGlcNS (1) and its glycol-split (gs) counterpart GlcNS6S-gsGlcA-1,6anGlcNS (2) from glucose...
November 23, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27878117/gpc-3-in-hepatocellular-carcinoma-current-perspectives
#13
REVIEW
Yongle Wu, Hui Liu, Huiguo Ding
Glypican-3 (GPC3), a member of heparan sulfate proteoglycans, attaches to the cell membrane and is frequently observed to be elevated in hepatocellular carcinoma (HCC). However, GPC3 is not detected in normal liver tissues and benign liver lesions. Consequently, GPC3 is currently being used as a diagnostic biomarker and HCC-specific positron emission computed tomography probe to identify HCCs in normal liver tissues and benign liver lesions. The overexpression of GPC-3 in serum or liver tissue also predicts poor prognosis for HCC patients...
2016: Journal of Hepatocellular Carcinoma
https://www.readbyqxmd.com/read/27875780/vp1-residues-around-the-five-fold-axis-of-enterovirus-a71-mediate-heparan-sulfate-interaction
#14
Chee Wah Tan, I-Ching Sam, Vannajan Sanghiran Lee, Hui Vern Wong, Yoke Fun Chan
Enterovirus A71 (EV-A71) is a neurotropic enterovirus that uses heparan sulfate as an attachment receptor. The molecular determinants of EV-A71-heparan sulfate interaction are unknown. With In silico heparin docking and mutagenesis of all possible lysine residues in VP1, we identified that K162, K242 and K244 are responsible for heparin interaction and inhibition. EV-A71 mutants with K242A and K244A rapidly acquired compensatory mutations, T100K or E98A, and Q145R-T237N respectively, which restored the heparin-binding phenotype...
November 19, 2016: Virology
https://www.readbyqxmd.com/read/27866326/the-neuroprotective-peptide-poly-arginine-12-r12-reduces-cell-surface-levels-of-nmda-nr2b-receptor-subunit-in-cortical-neurons-investigation-into-the-involvement-of-endocytic-mechanisms
#15
Gabriella MacDougall, Ryan S Anderton, Adam B Edwards, Neville W Knuckey, Bruno P Meloni
We have previously reported that cationic poly-arginine and arginine-rich cell-penetrating peptides display high-level neuroprotection and reduce calcium influx following in vitro excitotoxicity, as well as reduce brain injury in animal stroke models. Using the neuroprotective peptides poly-arginine R12 (R12) and the NR2B9c peptide fused to the arginine-rich carrier peptide TAT (TAT-NR2B9c; also known as NA-1), we investigated the mechanisms whereby poly-arginine and arginine-rich peptides reduce glutamate-induced excitotoxic calcium influx...
November 20, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27858357/surface-plasmon-resonance-analysis-of-heparin-binding-angiogenic-growth-factors
#16
Marco Rusnati, Antonella Bugatti
Surface plasmon resonance (SPR) is an optical technique to evaluate biomolecular interactions. Briefly, SPR measures the capacity of two molecules to bind each other by detecting reflected light from a prism-gold film interface. One of the two putative interactants (called ligand) is chemically immobilized onto the gold film. When the sensor is exposed to a sample containing the second interactant (called analyte), its binding to the immobilized ligand causes a change of the refractive index of the material above the gold surface that is monitored as a real-time graph of the response units against time, producing a real-time graph called sensorgram...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27854239/kshv-entry-and-trafficking-in-target-cells-hijacking-of-cell-signal-pathways-actin-and-membrane-dynamics
#17
REVIEW
Binod Kumar, Bala Chandran
Kaposi's sarcoma associated herpesvirus (KSHV) is etiologically associated with human endothelial cell hyperplastic Kaposi's sarcoma and B-cell primary effusion lymphoma. KSHV infection of adherent endothelial and fibroblast cells are used as in vitro models for infection and KSHV enters these cells by host membrane bleb and actin mediated macropinocytosis or clathrin endocytosis pathways, respectively. Infection in endothelial and fibroblast cells is initiated by the interactions between multiple viral envelope glycoproteins and cell surface associated heparan sulfate (HS), integrins (α3β1, αVβ3 and αVβ5), and EphA2 receptor tyrosine kinase (EphA2R)...
November 14, 2016: Viruses
https://www.readbyqxmd.com/read/27853671/heparanase-inhibitors-facilitate-the-assembly-of-the-basement-membrane-in-artificial-skin
#18
Makoto Tsunenaga
Recent research suggests that the basement membrane at the dermal-epidermal junction of the skin plays an important role in maintaining a healthy epidermis and dermis, and repeated damage to the skin can destabilize the skin and accelerate the aging process. Skin-equivalent models are suitable for studying the reconstruction of the basement membrane and its contribution to epidermal homeostasis because they lack the basement membrane and show abnormal expression of epidermal differentiation markers. By using these models, it has been shown that reconstruction of the basement membrane is enhanced not only by supplying basement membrane components, but also by inhibiting proteinases such as urokinase and matrix metalloproteinase...
August 2016: Current Tissue Engineering
https://www.readbyqxmd.com/read/27852738/contributions-of-rapid-neuromuscular-transmission-to-the-fine-control-of-acoustic-parameters-of-birdsong
#19
Caitlin Mencio, Balagurunathan Kuberan, Franz Goller
Neural control of complex vocal behaviors, such as birdsong and speech, requires integration of biomechanical nonlinearities through muscular output. Although control of airflow and tension of vibrating tissues are known functions of vocal muscles, it remains unclear how specific muscle characteristics contribute to specific acoustic parameters. To address this gap, we removed heparan sulfate chains using heparitinases to subtly perturb neuromuscular transmission in the syrinx of adult male zebra finches (Taeniopygia guttata)...
November 16, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27845251/heparan-sulfate-heparin-glycosaminoglycan-binding-alters-inhibitory-profile-and-enhances-anticoagulant-function-of-conserved-amblyomma-americanum-tick-saliva-serpin-19
#20
Željko M Radulović, Albert Mulenga
Some serine protease inhibitor (serpin) regulators of essential life pathways bind glycosaminoglycans (GAGs) to enhance inhibitory functions and achieve physiologically relevant rates. This study demonstrates that highly conserved Amblyomma americanum tick saliva serpin 19 (AAS19), a broad-spectrum inhibitor of hemostasis and inflammation system proteases and anticoagulant, can bind heparan sulfate/heparin (HS)GAGs and that this interaction alters its function. Substrate hydrolysis and unpaired t-test analyses revealed that HSGAG binding caused rAAS19 inhibitory activity to: (i) significantly increase against blood clotting factors (f) IIa (thrombin) and fIXa, (ii) significantly reduce against fXa and fXIIa and (iii) moderate to no effect against trypsin, kallikrein, papain, and plasmin...
November 12, 2016: Insect Biochemistry and Molecular Biology
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