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Heparan sulfate

Weiwei Ruan, Li Cao, Zhonghua Chen, Mingxiang Kong, Qing Bi
Hereditary multiple osteochondroma (HMO) is an autosomal dominant genetic disorder characterized by multiple outgrowing bony tumors capped by cartilage, generally affecting the metaphyses. The disease is known as hereditary multiple exostoses, familial exostosis, multiple cartilaginous exostoses or hereditary malformation of cartilage. The prevalence of HMO in Europe and the Unites States is ~1:100,000, although it has not been reported in China. The disease is often accompanied by pain, asymmetry and skeletal malformations, including forearm and leg bending deformities, limb length discrepancies, and knee internal and external rotation abnormalities...
April 2018: Oncology Letters
Michihito Sasaki, Paulina D Anindita, Naoto Ito, Makoto Sugiyama, Michael Carr, Hideo Fukuhara, Toyoyuki Ose, Katsumi Maenaka, Ayato Takada, William W Hall, Yasuko Orba, Hirofumi Sawa
Rabies virus (RABV) is the causative agent of fatal neurological disease. Cellular attachment is the initial and essential step for viral infections. Although extensive studies have demonstrated that RABV utilizes various target cell molecules to mediate infection, no specific molecule has been identified as an attachment factor for RABV infection. Here we demonstrate that cellular heparan sulfate (HS) supports RABV adhesion and subsequent entry into target cells. Enzymatic removal of HS reduced the cellular susceptibility to RABV infection and heparin, a highly sulfated form of HS, blocked viral adhesion and infection...
February 26, 2018: Journal of Infectious Diseases
Rafael S Aquino, Yvonne Hui-Fang Teng, Pyong Woo Park
Syndecan-1 (Sdc1) is a major cell surface heparan sulfate (HS) proteoglycan of epithelial cells, a cell type targeted by many bacterial pathogens early in their pathogenesis. Loss of Sdc1 in mice is a gain-of-function mutation that significantly decreases the susceptibility to several bacterial infections, suggesting that subversion of Sdc1 is an important virulence strategy. HS glycosaminoglycan (GAG) chains of cell surface Sdc1 promote bacterial pathogenesis by facilitating the attachment of bacteria to host cells...
March 9, 2018: Biochemical Society Transactions
Yuejie Zhao, Jeong Yeh Yang, David F Thieker, Yongmei Xu, Chengli Zong, Geert-Jan Boons, Jian Liu, Robert J Woods, Kelley W Moremen, I Jonathan Amster
Roundabout 1 (Robo1) interacts with its receptor Slit to regulate axon guidance, axon branching, and dendritic development in the nervous system and to regulate morphogenesis and many cell functions in the nonneuronal tissues. This interaction is known to be critically regulated by heparan sulfate (HS). Previous studies suggest that HS is required to promote the binding of Robo1 to Slit to form the minimal signaling complex, but the molecular details and the structural requirements of HS for this interaction are still unclear...
March 8, 2018: Journal of the American Society for Mass Spectrometry
Ja-Hyun Koo, Heeseok Yoon, Won-Ju Kim, Donghun Cha, Je-Min Choi
Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that regulates cellular responses such as proteasomal degradation and DNA repair upon interaction with its substrate. We identified a highly cationic region within the PAR-binding motif of Iduna; the region was similar among various species and showed amino acid sequence similarity with that of known cell-penetrating peptides (CPPs). We hypothesized that this Iduna-derived cationic sequence-rich peptide (Iduna) could penetrate the cell membrane and deliver macromolecules into cells...
March 8, 2018: International Journal of Molecular Sciences
Zengli Zhang, Hanyi Jiang, Yongsheng Wang, Minhua Shi
Background: Due to high metastasis and recurrence rate. Recent studies indicated that epithelial-to-mesenchymal transition (EMT) was involved in the progression and metastasis in cancer. Some reports also indicate that HS3ST3B1 played a role in angiogenesis and the proliferation of cancer cells. In this study, we aim to investigate its role in non-small cell lung cancer (NSCLC) . Materials and Methods: All cell lines were purchased from ATCC and cultured in our central lab...
January 2018: Journal of Cancer Research and Therapeutics
Weigang Lu, Chengli Zong, Pradeep Chopra, Lauren Pepi, Yongmei Xu, Jian Liu, I Jonathan Amster, Geert-Jan Boons
A chemoenzymatic approach has been developed for the preparation of diverse libraries of heparan sulfate (HS) oligosaccharides. It employs chemically synthesized oligosaccharides having a chemical entity at a GlcN residue, which in unanticipated manners influences the site of modification of NST, C5-Epi/2-OST and 6-OST1/6-OST3 resulting in oligosaccharides differing in N/O-sulfation and epimerization pattern. The enzymatic transformations defined fine substrate requirements of NST, C5-Epi, 2-OST and 6-OST.
March 7, 2018: Angewandte Chemie
Maristela P Rangel, Vanessa K de Sá, Tabatha Prieto, João Roberto M Martins, Eloísa R Olivieri, Dirce Carraro, Teresa Takagaki, Vera Luiza Capelozzi
Matrix proteoglycans (PGs) have shown promise as biomarker in malignancies. We employed agarose gel eletrophoresis, quantitative real- time reverse transcription-polymerase chain reaction and immunohistochemistry to evaluate the content of sulfated glicosaminoglycans (chondroitin sulfate and heparan sulfate) and expression of PG (biglycan, glypican, perlecan, syndecan e versican) in patient-matched normal and tumor tissues obtained from resected specimens of lung cancer. A significant increase of heparan sulfate (HS) and chondroitin sulfate (CS) concentrations was found in tumor tissue samples when compared to normal lung tissue samples...
March 3, 2018: Glycoconjugate Journal
Patience Sanderson, Morgan Stickney, Franklin E Leach, Qiangwei Xia, Yanlei Yu, Fuming Zhang, Robert J Linhardt, I Jonathan Amster
Reverse polarity capillary zone electrophoresis coupled to negative ion mode mass spectrometry (CZE-MS) is shown to be an effective and sensitive tool for the analysis of glycosaminoglycan mixtures. Covalent modification of the inner wall of the separation capillary with neutral or cationic reagents produces a stable and durable surface that provides reproducible separations. By combining CZE-MS with a cation-coated capillary and a sheath flow interface, a rapid and reliable method has been developed for the analysis of sulfated oligosaccharides from dp4 to dp12...
February 24, 2018: Journal of Chromatography. A
Thomas N Wight
The content of proteoglycans (PGs) is low in the extracellular matrix (ECM) of vascular tissue, but increases dramatically in all phases of vascular disease. Early studies demonstrated that glycosaminoglycans (GAGs) including chondroitin sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS) and heparan sulfate (HS) accumulate in vascular lesions in both humans and in animal models in areas of the vasculature that are susceptible to disease initiation (such as at branch points) and are frequently coincident with lipid deposits...
February 27, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Albert Lee, Dimitrios Karamichos, Obianamma E Onochie, Audrey E K Hutcheon, Celeste B Rich, James D Zieske, Vickery Trinkaus-Randall
Deposition of matrix proteins during development and repair is critical to the transparency of the cornea. While many cells respond to a hypoxic state that can occur in a tumor, the cornea is exposed to hypoxia during development prior to eyelid opening and during the diurnal sleep cycle where oxygen levels can drop from 21% to 8%. In this study, we used 2 three-dimensional (3-D) models to examine how stromal cells respond to periods of acute hypoxic states. The first model, a stromal construct model, is a 3-D stroma-like construct that consists of human corneal fibroblasts (HCFs) stimulated by a stable form of ascorbate for 1, 2, and 4 weeks to self-assemble their own extracellular matrix...
February 26, 2018: Experimental Eye Research
Y L Zhang, L Guan, Y M Zheng, Z M Zhao, L J Mao, S Q Li, J Y Zhao
Objective: In order to explore the role of heparan sulfate (HS) during the pathogenesis of acute respiratory distress syndrome (ARDS) , the protective effect of HS and its fragments against extracellular histones was compared. Methods: Calf thymus histones (CTH) were injected via femoral vein to induce ARDS in rats. HS, HS fragments or saline was intraperitoneally injected (10mg/kg, Q6h, 24h) to test the protective effect against CTH. The ratio of wet/dry lung weight, protein content in bronchoalveolar lavage fluid (BALF) , total leukocyte and neutrophil count in BALF were measured...
January 20, 2018: Chinese Journal of Industrial Hygiene and Occupational Diseases
Makoto I Kanai, Myung-Jun Kim, Takuya Akiyama, Masahiko Takemura, Kristi Wharton, Michael B O'Connor, Hiroshi Nakato
Despite the importance of precisely regulating stem cell division, the molecular basis for this control is still elusive. Here, we show that surface glia in the developing Drosophila brain play essential roles in regulating the proliferation of neural stem cells, neuroblasts (NBs). We found that two classes of extracellular factors, Dally-like (Dlp), a heparan sulfate proteoglycan, and Glass bottom boat (Gbb), a BMP homologue, are required for proper NB proliferation. Interestingly, Dlp expressed in perineural glia (PG), the most outer layer of the surface glia, is responsible for NB proliferation...
February 27, 2018: Scientific Reports
R Bologna-Molina, T Mikami, V Pereira-Prado, G Tapia-Repetto, F R Pires, R Carlos, A Mosqueda-Taylor
Primordial odontogenic tumor (POT) is composed of variably cellular myxoid connective tissue, surrounded by cuboidal to columnar odontogenic epithelium resembling the inner epithelium of the enamel organ, which often invaginates into the underlying connective tissue. The tumor is delimited at least partially by a thin fibrous capsule. It derives from the early stages of tooth development. Syndecan-1 is a heparan sulfate proteoglycan that has a physiological role in several cellular functions, including maintenance of the epithelial architecture, cell-to-cell adhesion and interaction of cells with extracellular matrix, and with diverse growth factors, stimulating cell proliferation...
March 2018: Oral Diseases
Megan S Lord, Fengying Tang, Jelena Rnjak-Kovacina, James G W Smith, James Melrose, John M Whitelock
Perlecan, or heparan sulfate proteoglycan 2 (HSPG2), is a ubiquitous heparan sulfate proteoglycan that has major roles in tissue and organ development and wound healing by orchestrating the binding and signaling of mitogens and morphogens to cells in a temporal and dynamic fashion. In this review, its roles in fibrosis are reviewed by drawing upon evidence from tissue and organ systems that undergo fibrosis as a result of an uncontrolled response to either inflammation or traumatic cellular injury leading to an over production of a collagen-rich extracellular matrix...
February 20, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Samantha J Katner, Wyatt E Johnson, Erica J Peterson, Phillip Page, Nicholas P Farrell
We present spectroscopic and biophysical approaches to examine the affinity of metal-ammine coordination complexes for heparin as a model for heparan sulfate (HS). Similar to nucleic acids, the highly anionic nature of heparin means it is associated in vivo with physiologically relevant cations, and this work extends their bioinorganic chemistry to substitution-inert metal-ammine compounds (M). Both indirect and direct assays were developed. M compounds are competitive inhibitors of methylene blue (MB)-heparin binding, and the change in the absorbance of the dye in the presence or absence of heparin can be used as an indirect reporter of M-heparin affinity...
February 23, 2018: Inorganic Chemistry
Ying-Xia Tan, Hao Cui, Lu-Ming Wan, Feng Gong, Xiao Zhang, Israel Vlodavsky, Jin-Ping Li
Heparanase, an endo-glucuronidase that specifically cleaves heparan sulfate, is upregulated in several pathological conditions. In this study, we aimed to find a correlation of heparanase expression and platelets production. In the transgenic mice overexpressing human heparanase (Hpa-tg), hematological analysis of blood samples revealed a significantly higher number of platelets in comparison with wild-type (Ctr) mice, while no significant difference was found in leukocytes and red blood cell number between the two groups...
February 19, 2018: Glycobiology
Fengying Tang, Megan S Lord, William B Stallcup, John M Whitelock
Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell surface proteoglycan highly expressed by tumor, perivascular and oligodendrocyte cells and known to be involved cell adhesion and migration. This study showed that CSPG4 was present as a proteoglycan on the cell surface of two melanoma cell lines, MM200 and Me1007, as well as shed into the conditioned medium. CSPG4 from the two melanoma cell lines differed in the amount of chondroitin sulfate (CS) decoration, as well as the way the protein core was fragmented...
February 15, 2018: Journal of Biochemistry
Hideki Kusunoki, Toshiyuki Tanaka, Toshiyuki Kohno, Kazuhiko Matsuhashi, Kazuo Hosoda, Kaori Wakamatsu, Isao Hamaguchi
Entry of human T-cell lymphotropic virus type 1 (HTLV-1) into host cells is mainly mediated by interactions between the viral envelope glycoprotein surface unit (SU) and three host receptors: glucose transporter type 1, heparin/heparan sulfate proteoglycan, and neuropilin-1 (Nrp1). Here, we analyzed the interaction between HTLV-1 SU and Nrp1 using nuclear magnetic resonance and isothermal titration calorimetry. We found that two SU peptides, residues 85-94 and residues 304-312, bound directly to the Nrp1 b1 domain with affinities of 7...
February 16, 2018: Biochimica et Biophysica Acta
Julia P Steringer, Walter Nickel
As illustrated by a diverse set of examples in this special issue, multiple mechanisms of protein secretion have been identified in eukaryotes that do not involve the endoplasmic reticulum (ER) and the Golgi apparatus. Here we focus on the type I pathway with Fibroblast Growth Factor 2 (FGF2) being the most prominent example. Unconventional secretion of FGF2 from cells is mediated by direct protein translocation across the plasma membrane. A unique feature of this process is the ability of FGF2 to form its own membrane translocation intermediate through oligomerization and membrane insertion...
February 16, 2018: Seminars in Cell & Developmental Biology
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