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Dermatan sulfate

Manuela Viola, Kathrin Brüggemann, Evgenia Karousou, Ilaria Caon, Elena Caravà, Davide Vigetti, Burkhard Greve, Christian Stock, Giancarlo De Luca, Alberto Passi, Martin Götte
Proteoglycans and glycosaminoglycans modulate numerous cellular processes relevant to tumour progression, including cell proliferation, cell-matrix interactions, cell motility and invasive growth. Among the glycosaminoglycans with a well-documented role in tumour progression are heparan sulphate, chondroitin/dermatan sulphate and hyaluronic acid/hyaluronan. While the mode of biosynthesis differs for sulphated glycosaminoglycans, which are synthesised in the ER and Golgi compartments, and hyaluronan, which is synthesized at the plasma membrane, these polysaccharides partially compete for common substrates...
October 15, 2016: Glycoconjugate Journal
Francyne Kubaski, Robert W Mason, Akiko Nakatomi, Haruo Shintaku, Li Xie, Naomi N van Vlies, Heather Church, Roberto Giugliani, Hironori Kobayashi, Seiji Yamaguchi, Yasuyuki Suzuki, Tadao Orii, Toshiyuki Fukao, Adriana M Montaño, Shunji Tomatsu
BACKGROUND: Mucopolysaccharidoses (MPS) are a group of inborn errors of metabolism that are progressive and usually result in irreversible skeletal, visceral, and/or brain damage, highlighting a need for early diagnosis. METHODS: This pilot study analyzed 2862 dried blood spots (DBS) from newborns and 14 DBS from newborn patients with MPS (MPS I, n = 7; MPS II, n = 2; MPS III, n = 5). Disaccharides were produced from polymer GAGs by digestion with chondroitinase B, heparitinase, and keratanase II...
October 7, 2016: Journal of Inherited Metabolic Disease
José L Neira, Encarnación Medina-Carmona, José G Hernández-Cifre, Laia Montoliu-Gaya, Ana Cámara-Artigás, Ilham Seffouh, Florence Gonnet, Régis Daniel, Sandra Villegas, José García de la Torre, Angel L Pey, Fuchuan Li
Sulfatases catalyze hydrolysis of sulfate groups. They have a key role in regulating the sulfation states that determine the function of several scaffold molecules. Currently, there are not studies of the conformational stability of endosulfatases. In this work, we describe the structural features and conformational stability of a 4-O-endosulfatase (EndoV) from a marine bacterium, which removes specifically the 4-O-sulfate from chondroitin sulfate/dermatan sulfate. For that purpose, we have used several biophysical techniques, namely, fluorescence, circular dichroism (CD), FTIR spectroscopy, analytical ultracentrifugation (AUC), differential scanning calorimetry (DSC), mass spectrometry (MS), dynamic light scattering (DLS) and size exclusion chromatography (SEC)...
September 27, 2016: Biochimie
Kyohei Higashi, Keita Takeda, Ann Mukuno, Yusuke Okamoto, Sayaka Masuko, Robert J Linhardt, Toshihiko Toida
Glycosaminoglycans (GAGs) including chondroitin sulfate (CS), dermatan sulfate, heparin, heparan sulfate and keratan sulfate (KS) are linear, sulfated repeating disaccharide sequences containing hexosamine and uronic acid (or galactose (Gal) in the case of KS).  Among the GAGs, CS shows structural variations, such as sulfation patterns and fucosylation, which are responsible for their physiological functions through CS interaction with CS-binding proteins.  Here, we solved the structure of KS-branched chondroitin sulfate E derived from a clam, Mactra chinensis...
September 19, 2016: Biochemical Journal
Konstantina Karamanou, Diana Carolina Restrepo Espinosa, Anneliese Fortuna-Costa, Mauro Sérgio Gonçalves Pavão
Glycosaminoglycans with unique sulfation patterns have been identified in different species of ascidians (sea squirts), a group of marine invertebrates of the Phylum Chordata, sub-phylum Tunicata (or Urochordata). Oversulfated dermatan sulfate composed of [4-α-L-IdoA-(2-O-SO3)(-1) → 3-β-D-GalNAc(4-OSO3)(-1)]n repeating disaccharide units is found in the extracellular matrix of several organs, where it seems to interact with collagen fibers. This dermatan sulfate co-localizes with a decorin-like protein, as indicated by immunohistochemical analysis...
September 10, 2016: Glycoconjugate Journal
Sumit Bhattacharyya, Leo Feferman, Joanne K Tobacman
Aerobic respiration is required for optimal efficiency of metabolism in mammalian cells. Under circumstances when oxygen utilization is impaired, cells survive by anerobic metabolism. The malignant cell has cultivated the use of anerobic metabolism in an aerobic environment, the Warburg effect, but the explanation for this preference is not clear. This paper presents evidence that deficiency of the enzyme arylsulfatase B (ARSB; N-acetylgalactosamine 4-sulfatase), either innate or acquired, helps to explain the Warburg phenomenon...
2016: Scientific Reports
Takayuki Yokoi, Kentarou Yokoi, Kazumasa Akiyama, Takashi Higuchi, Yohta Shimada, Hiroshi Kobayashi, Taku Sato, Toshiaki Ohteki, Makoto Otsu, Hiromitsu Nakauchi, Hiroyuki Ida, Toya Ohashi
Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disease caused by the deficient activity of iduronate 2-sulfatase (IDS), which is involved in the lysosomal catabolism of the glycosaminoglycans (GAGs) dermatan and heparan sulfate. Such a deficiency leads to the accumulation of undegraded GAGs in some organs. Although enzyme replacement therapy is available as a treatment of MPS II, there are some limitations, such as the requirement of weekly administration for whole life. To avoid such limitations, hematopoietic cell transplantation (HSCT) is a possible alternative...
August 21, 2016: Molecular Genetics and Metabolism
F Maccari, N C Sorrentino, V Mantovani, F Galeotti, A Fraldi, N Volpi
Mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo A) is a neurodegenerative lysosomal storage disorder caused by the deficiency of sulphamidase enzyme (SGSH) leading to accumulation of heparan sulfate (HS). We quantitatively and structurally characterize primary stored HS and other glycosaminoglycans (GAGs) possibly accumulated through a secondary storage in brain, liver, kidney and lung of MPS IIIA mouse model. This analysis was also performed in MPS IIIA mice upon the intravenous treatment with an engineered human sulphamidase (chimeric hSGSH) capable to increase its secretion from the liver and to cross the blood-brain barrier...
September 1, 2016: Metabolic Brain Disease
Takato Hara, Eiko Yoshida, Yasuhiro Shinkai, Chika Yamamoto, Yasuyuki Fujiwara, Yoshito Kumagai, Toshiyuki Kaji
Proteoglycans are macromolecules that consist of a core protein and one or more glycosaminoglycan side chains. A small leucine-rich dermatan sulfate proteoglycan, biglycan, is one of the predominant types of proteoglycans synthesized by vascular endothelial cells; however, the physiological functions of biglycan are not completely understood. In the present study, bovine aortic endothelial cells in culture were transfected with small interfering RNAs for biglycan, and the expression of other proteoglycans was examined...
September 1, 2016: Journal of Cellular Biochemistry
Christiane Auray-Blais, Pamela Lavoie, Shunji Tomatsu, Vassili Valayannopoulos, John J Mitchell, Julian Raiman, Maxime Beaudoin, Bruno Maranda, Joe T R Clarke
Mucopolysaccharidoses (MPSs) are a group of disorders resulting from primary defects in lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). Depending on the specific enzyme defect, the catabolism of one or more GAGs is blocked leading to accumulation in tissues and biological fluids. GAG measurements are important for high-risk screening, diagnosis, monitoring treatment efficacy, and patient follow up. The dimethylmethylene blue (DMB) spectrophotometric method commonly used in most biochemical genetics laboratories relies on a non-specific total GAG analysis which has led to false positive results, and even false negative results (mainly for MPS III and IV patients)...
September 14, 2016: Analytica Chimica Acta
Tom Plug, Joost C M Meijers
BACKGROUND: Thrombin-activatable fibrinolysis inhibitor (TAFI) is a proenzyme that, once activated, attenuates fibrinolysis by removing C-terminal lysine residues from partially degraded fibrin. TAFI can be activated by thrombin or plasmin via a cleavage at Arg92 that removes the activation peptide from the enzyme, TAFIa. Thrombomodulin enhances thrombin-mediated TAFI activation and glycosaminoglycans enhance plasmin-mediated TAFI activation. The aim of this study was to investigate whether there are other anionic molecules that function as a cofactor for thrombin- or plasmin-mediated TAFI activation...
October 2016: Thrombosis Research
Hiroko Habuchi, Takahiro Ushida, Osami Habuchi
BACKGROUND: Chondroitin/dermatan sulfate (CS/DS) rich in N-acetylgalactosamine 4,6-bissulfate (GalNAc(4,6SO4)) residues is present as decorin and/or biglycan in mouse liver, and GalNAc(4,6SO4) residues disappeared completely in N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST) knockout (KO) mice. The aim of this study was to investigate whether CS/DS rich in GalNAc(4,6SO4) residues participate in the progression or resolution of liver fibrosis. METHODS: Wild type (WT) and GalNAc4S-6ST KO mice were treated with CCl4 for 5 weeks...
August 2016: Heliyon
Shumin Wang, Kazuyuki Sugahara, Fuchuan Li
Sulfatases that specifically catalyze the hydrolysis of the sulfate groups on chondroitin sulfate (CS)/dermatan sulfate (DS) poly- and oligosaccharides belong to the formylglycine-dependent family of sulfatases and have been widely found in various mammalian and bacterial organisms. However, only a few types of CS/DS sulfatase have been identified so far. Recently, several novel CS/DS sulfatases have been cloned and characterized. Advanced studies have provided significant insight into the biological function and mechanism of action of CS/DS sulfatases...
August 15, 2016: Glycoconjugate Journal
Renáta Gáspár, Márton Pipicz, Fatime Hawchar, Dávid Kovács, Luna Djirackor, Anikó Görbe, Zoltán V Varga, Mónika Kiricsi, Goran Petrovski, Attila Gácser, Csaba Csonka, Tamás Csont
AIMS: Exogenously administered biglycan (core protein with high-molecular weight glycosaminoglycan chains) has been shown to protect neonatal cardiomyocytes against simulated ischemia/reperfusion injury (SI/R), however, the mechanism of action is not clear. In this study we aimed to investigate, which structural component of biglycan is responsible for its cardiocytoprotective effect and to further explore the molecular mechanisms involved in the cytoprotection. METHODS AND RESULTS: A pilot study was conducted to demonstrate that both native (glycanated) and deglycanated biglycan can attenuate cell death induced by SI/R in a dose-dependent manner in primary neonatal cardiomyocytes isolated from Wistar rats...
August 9, 2016: Journal of Molecular and Cellular Cardiology
Ye Li, Zhenya Chen, Zhao Zhou, Qipeng Yuan
Chondroitinases (ChSases) are a family of polysaccharide lyases that can depolymerize high molecular weight chondroitin sulfate (CS) and dermatan sulfate (DS). In this study, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is stably expressed in different cells like normal cells and cancer cells and the expression is relatively insensitive to experimental conditions, was expressed as a fusion protein with ChSase ABC I. Results showed that the expression level and enzyme activity of GAPDH-ChSase ABC I were about 2...
December 2016: Protein Expression and Purification
P Przybylowski, G Wasilewski, E Koc-Żórawska, J Malyszko
BACKGROUND: Endocan is a novel soluble dermatan sulfate proteoglycan derived from endothelium. It has the capacity of binding to different biologically active molecules associated with cellular signaling, adhesion, and regulating proliferation, differentiation, migration, and adhesion of different cell types in health and pathology. Its elevated level is connected with endothelial activation, neovascularization, and inflammation or carcinogenesis. METHODS: The level of serum endocan among 131 heart transplant recipients on 3-drug immunosuppression (calcineurin inhibitor, mycophenolate mofetil/mycophenolic acid, steroid) in correlation with other markers of endothelial damage was determined...
June 2016: Transplantation Proceedings
Ariane Nimptsch, Jürgen Schiller
RATIONALE: If carbohydrates are investigated by nuclear magnetic resonance (NMR) spectroscopy, they are normally dissolved in deuterated solvents, such as D2 O. The incorporation of deuterium leads to a high complexity of subsequently recorded mass spectra and reduced sensitivity because different deuterated ions become detectable. Here, we demonstrate that the applied matrix-assisted laser desorption/ionization (MALDI) matrix solution has a considerable impact on the observed isotopic distribution...
October 15, 2016: Rapid Communications in Mass Spectrometry: RCM
Jing Zhao, Xinyue Liu, Chelsea Kao, Emily Zhang, Quanhong Li, Fuming Zhang, Robert J Linhardt
Langerin, a C-type lectin, is expressed in Langerhans cells. It was reported that langerin binds sulfated glycans, which is an important initial step for its role in blocking human immunodeficiency virus (HIV) transmission by capturing HIV pathogens and mediating their internalization into Birbeck granules for their elimination. It is fundamentally important to understand these interactions at the molecular level for the design of new highly specific therapeutic agents for HIV. Surface plasmon resonance (SPR), which allows for the real-time, direct, quantitative analysis of the label-free molecular interactions, has been used successfully for biophysical characterization of glycosaminoglycan (GAG)-protein interactions...
August 16, 2016: Biochemistry
Megan S Lord, Bill Cheng, Fengying Tang, J Guy Lyons, Jelena Rnjak-Kovacina, John M Whitelock
Heparin is a carbohydrate anticoagulant used clinically to prevent thrombosis, however impurities can limit its efficacy. Here we report the biosynthesis of heparin-like heparan sulfate via the recombinant expression of human serglycin in human cells. The expressed serglycin was also decorated with chondroitin/dermatan sulfate chains and the relative abundance of these glycosaminoglycan chains changed under different concentrations of glucose in the culture medium. The recombinantly expressed serglycin produced with 25mM glucose present in the culture medium was found to possess anticoagulant activity one-seventh of that of porcine unfractionated heparin, demonstrating that bioengineered human heparin-like heparan sulfate may be a safe next-generation pharmaceutical heparin...
July 18, 2016: Metabolic Engineering
Sophie Mathieu, Bernard Henrissat, Flavien Labre, Gudmund Skjåk-Bræk, William Helbert
Alginate, the main cell-wall polysaccharide of brown algae, is composed of two residues: mannuronic acid (M-residues) and, its C5-epimer, guluronic acid (G-residues). Alginate lyases define a class of enzymes that cleave the glycosidic bond of alginate by β-elimination. They are classified according to their ability to recognize the distribution of M- and G-residues and are named M-, G- or MG-lyases. In the CAZy database, alginate lyases have been grouped by sequence similarity into seven distinct polysaccharide lyase families...
2016: PloS One
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