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Glycoconjugate Journal Jun 2017Glycosaminoglycans with unique sulfation patterns have been identified in different species of ascidians (sea squirts), a group of marine invertebrates of the Phylum... (Review)
Review
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-SO) → 3-β-D-GalNAc(4-OSO)] 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. Low sulfated heparin/heparan sulfate-like glycans composed mainly of [4-α-L-IdoA-(2-OSO) → 4-α-D-GlcN(SO) (6-O-SO)] and [4-α-L-IdoA-(2-O-SO) → 4-α-D-GlcN(SO)] have also been described in ascidians. These heparin-like glycans occur in intracellular granules of oocyte assessory cells, named test cells, in circulating basophil-like cells in the hemolymph, and at the basement membrane of different ascidian organs. In this review, we present an overview of the structure, distribution, extracellular and intracellular localization of the sulfated glycosaminoglycans in different species and tissues of ascidians. Considering the phylogenetic position of the subphylum Tunicata in the phylum Chordata, a careful analysis of these data can reveal important information about how these glycans evolved from invertebrate to vertebrate animals.
Topics: Animal Structures; Animals; Carbohydrate Conformation; Carbohydrate Sequence; Collagen; Decorin; Dermatan Sulfate; Disaccharides; Extracellular Matrix; Hemolymph; Phylogeny; Urochordata
PubMed: 27614617
DOI: 10.1007/s10719-016-9728-5 -
International Journal of Molecular... Mar 2022Pleiotrophin (PTN) is a neurotrophic factor that participates in the development of the embryonic central nervous system (CNS) and neural stem cell regulation by means...
Pleiotrophin (PTN) is a neurotrophic factor that participates in the development of the embryonic central nervous system (CNS) and neural stem cell regulation by means of an interaction with sulfated glycosaminoglycans (GAGs). Chondroitin sulfate (CS) is the natural ligand in the CNS. We have previously studied the complexes between the tetrasaccharides used here and MK (Midkine) by ligand-observed NMR techniques. The present work describes the interactions between a tetrasaccharide library of synthetic models of CS-types and mimetics thereof with PTN using the same NMR transient techniques. We have concluded that: (1) global ligand structures do not change upon binding, (2) the introduction of lipophilic substituents in the structure of the ligand improves the strength of binding, (3) binding is weaker than for MK, (4) STD-NMR results are compatible with multiple binding modes, and (5) the replacement of GlcA for IdoA is not relevant for binding. Then we can conclude that the binding of CS derivatives to PTN and MK are similar and compatible with multiple binding modes of the same basic conformation.
Topics: Carrier Proteins; Chondroitin Sulfates; Cytokines; Dermatan Sulfate; Ligands; Oligosaccharides
PubMed: 35328448
DOI: 10.3390/ijms23063026 -
International Journal of Molecular... Apr 2019Glycosaminoglycans (GAGs) are a class of biomolecules expressed virtually on all mammalian cells and usually covalently attached to proteins, forming proteoglycans. They... (Review)
Review
Glycosaminoglycans (GAGs) are a class of biomolecules expressed virtually on all mammalian cells and usually covalently attached to proteins, forming proteoglycans. They are present not only on the cell surface, but also in the intracellular milieu and extracellular matrix. GAGs interact with multiple ligands, both soluble and insoluble, and modulate an important role in various physiological and pathological processes including cancer, bacterial and viral infections, inflammation, Alzheimer's disease, and many more. Considering their involvement in multiple diseases, their use in the development of drugs has been of significant interest in both academia and industry. Many GAG-based drugs are being developed with encouraging results in animal models and clinical trials, showcasing their potential for development as therapeutics. In this review, the role GAGs play in both the development and inhibition of cancer and inflammation is presented. Further, advancements in the development of GAGs and their mimetics as anti-cancer and anti-inflammatory agents are discussed.
Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Biological Mimicry; Biomimetics; Glycosaminoglycans; Humans; Inflammation; Neoplasms
PubMed: 31013618
DOI: 10.3390/ijms20081963 -
Data in Brief Jun 2023The data shown in this article are related to the published paper entitled "A novel 4--endosulfatase with high potential for the structure-function studies of...
The data shown in this article are related to the published paper entitled "A novel 4--endosulfatase with high potential for the structure-function studies of chondroitin sulfate/dermatan sulfate" in . In this article, the phylogenetic analysis, cloning, expression, purification, specificity and biochemical characteristics of the identified chondroitin sulfate/dermatan sulfate 4--endosulfatase (endoBI4SF) are described in detail. The recombinant endoBI4SF with a molecular mass of 59.13 kDa can can specifically hydrolyze the 4-- but not 2-- and 6--sulfate groups in the oligo-/polysaccharides of chondroitin sulfate/dermatan sulfate and show the maximum reaction rate in 50 mM Tris-HCl buffer (pH 7.0) at 50°C, which can be a very useful tool for the structural and functional studies of chondroitin sulfate/dermatan sulfate.
PubMed: 37113498
DOI: 10.1016/j.dib.2023.109139 -
The Journal of Histochemistry and... Nov 2020Versican is a large chondroitin sulfate/dermatan sulfate proteoglycan belonging to the aggrecan/lectican family. In adults, this proteoglycan serves as a structural... (Review)
Review
Versican is a large chondroitin sulfate/dermatan sulfate proteoglycan belonging to the aggrecan/lectican family. In adults, this proteoglycan serves as a structural macromolecule of the extracellular matrix in the brain and large blood vessels. In contrast, versican is transiently expressed at high levels during development and under pathological conditions when the extracellular matrix dramatically changes, including in the inflammation and repair process. There are many reports showing the upregulation of versican in cancer, which correlates with cancer aggressiveness. Versican has four classical splice variants, and all the variants contain G1 and G3 domains at N- and C-termini, respectively. There are two glycosaminoglycan attachment domains CSα and CSβ. The largest V0 variant contains both CSα and CSβ, V1 contains CSβ, V2 contains CSα, and the shortest G3 variant has neither of them. Versican degradation is initiated by cleavage at a site in the CSβ domain by ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteinases. The N-terminal fragment containing the G1 domain has been reported to exert various biological functions, although its mechanisms of action have not yet been elucidated. In this review, we describe the role of versican in inflammation and cancer and also address the biological function of versikine.
Topics: Animals; Extracellular Matrix; Humans; Inflammation; Neoplasms; Versicans
PubMed: 33131383
DOI: 10.1369/0022155420953922 -
International Journal of Molecular... Dec 2021Mucopolysaccharidosis type VI, or Maroteaux-Lamy syndrome, is a rare, autosomal recessive genetic disease, mainly affecting the pediatric age group. The disease is due... (Review)
Review
Mucopolysaccharidosis type VI, or Maroteaux-Lamy syndrome, is a rare, autosomal recessive genetic disease, mainly affecting the pediatric age group. The disease is due to pathogenic variants of the gene, coding for the lysosomal hydrolase N-acetylgalactosamine 4-sulfatase (arylsulfatase B, ASB). The enzyme deficit causes a pathological accumulation of the undegraded glycosaminoglycans dermatan-sulphate and chondroitin-sulphate, natural substrates of ASB activity. Intracellular and extracellular deposits progressively take to a pathological scenario, often severe, involving most organ-systems and generally starting from the osteoarticular apparatus. Neurocognitive and behavioral abilities, commonly described as maintained, have been actually investigated by few studies. The disease, first described in 1963, has a reported prevalence between 0.36 and 1.3 per 100,000 live births across the continents. With this paper, we wish to contribute an updated overview of the disease from the clinical, diagnostic, and therapeutic sides. The numerous in vitro and in vivo preclinical studies conducted in the last 10-15 years to dissect the disease pathogenesis, the efficacy of the available therapeutic treatment (enzyme replacement therapy), as well as new therapies under study are here described. This review also highlights the need to identify new disease biomarkers, potentially speeding up the diagnostic process and the monitoring of therapeutic efficacy.
Topics: Chondroitin Sulfates; Enzyme Replacement Therapy; Glycosaminoglycans; Humans; Mucopolysaccharidosis VI; N-Acetylgalactosamine-4-Sulfatase
PubMed: 34948256
DOI: 10.3390/ijms222413456 -
Current Molecular Medicine 2022Covalent conjugation of hyaluronidase with copolymeric glycosaminoglycans (GAG, heparin and dermatan sulfate) considerably inactivates the enzyme, while conjugation with...
Covalent conjugation of hyaluronidase with copolymeric glycosaminoglycans (GAG, heparin and dermatan sulfate) considerably inactivates the enzyme, while conjugation with polymeric GAG (chondroitin sulfate and hyaluronan) improves its stability. These effects are associated with structural differences of these GAG caused by С-5 epimerization of glucuronic and iduronic acid residues and different effects of (α[1 - 4] and α[1 - 3] relative to β[1 - 4] and β[1 - 3]) glycosidic bonds. Pronounced effects of galactose C-4 epimers (in comparison with glucose) and disaccharide mixture (lactose, cellobiose, maltose) on endoglycosidase activity of hyaluronidase emphasize the importance of its diversified multi-contact microenvironment. For a better understanding of the mechanisms regulating hyaluronidase activity, molecular docking and molecular dynamics were chosen. Stabilization effect of chondroitin ligands on heat inactivation of hyaluronidase was demonstrated. An increase in denaturation temperature by 10-15oC hampers blocking of the active site entrance and prevents the enzyme inactivation. Enzyme-GAG interactions were examined by molecular docking with molecular dynamic elaboration. Gradual chemical modification of hyaluronidase was based on the calculated sequence of preferential binding of GAG. Theoretically, covalent binding of chondroitin sulfate trimers at cs7 or cs7, cs1 and cs5 on the enzyme surface provides complete protection against heparin inhibition. Computational investigation of hyaluronidase microenvironment and interactions which limit the enzyme activity allows identification of the best GAG regulators of hyaluronidase endoglycosidase activity and their experimental verification.
Topics: Chondroitin Sulfates; Glycosaminoglycans; Heparin; Hyaluronoglucosaminidase; Ligands; Molecular Docking Simulation
PubMed: 35708105
DOI: 10.2174/1566524021666211018113204 -
Cells Oct 2020Scavenger receptors perform essential functions, critical to maintaining mammalian physiologic homeostasis by continuously clearing vast numbers of biomolecules from... (Review)
Review
Scavenger receptors perform essential functions, critical to maintaining mammalian physiologic homeostasis by continuously clearing vast numbers of biomolecules from blood, interstitial fluid and lymph. Stabilin-2 (Stab2) and the Hyaluronic Acid Receptor for Endocytosis (HARE), a proteolytic isoform of Stab2, are important scavenger receptors responsible for the specific binding and internalization (leading to degradation) of 22 discrete molecules, macromolecular complexes and cell types. One-third of these ligands are glycosaminoglycans (GAGs). Full-length Stab2, but not HARE, mediates efficient phagocytosis of apoptotic cells and bacteria via binding to target surface ligands. HARE, the C-terminal half of Stab2, mediates endocytosis of all the known soluble ligands. HA was the first ligand identified, in 1981, prior to receptor purification or cloning. Seven other GAG ligands were subsequently identified: heparin, dermatan sulfate, chondroitin and chondroitin sulfates A, C, D and E. Synthetic dextran sulfate is also a GAG mimic and ligand. HARE signaling during HA endocytosis was first discovered in 2008, and we now know that activation of HARE/Stab2 signaling is stimulated by receptor-mediated endocytosis or phagocytosis of many, but not all, of its ligands. This review focuses on the HARE-mediated GAG activation of intracellular signaling, particularly the Extracellular Signal-Regulated Kinase 1/2 pathway.
Topics: Amino Acid Sequence; Animals; Cell Adhesion Molecules, Neuronal; Endocytosis; Glycosaminoglycans; Humans; Intracellular Space; Macrophages; Signal Transduction
PubMed: 33126404
DOI: 10.3390/cells9112366 -
Developmental Dynamics : An Official... Jan 2018The nervous system coordinates the functions of most multicellular organisms and their response to the surrounding environment. Its development involves concerted... (Review)
Review
The nervous system coordinates the functions of most multicellular organisms and their response to the surrounding environment. Its development involves concerted cellular interactions, including migration, axon guidance, and synapse formation. These processes depend on the molecular constituents and structure of the extracellular matrices (ECM). An essential component of ECMs are proteoglycans, i.e., proteins containing unbranched glycan chains known as glycosaminoglycans (GAGs). A defining characteristic of GAGs is their enormous molecular diversity, created by extensive modifications of the glycans during their biosynthesis. GAGs are widely expressed, and their loss can lead to catastrophic neuronal defects. Despite their importance, we are just beginning to understand the function and mechanisms of GAGs in neuronal development. In this review, we discuss recent evidence suggesting GAGs have specific roles in neuronal patterning and synaptogenesis. We examine the function played by the complex modifications present on GAG glycans and their roles in regulating different aspects of neuronal patterning. Moreover, the review considers the function of proteoglycan core proteins in these processes, stressing their likely role as co-receptors of different signaling pathways in a redundant and context-dependent manner. We conclude by discussing challenges and future directions toward a better understanding of these fascinating molecules during neuronal development. Developmental Dynamics 247:54-74, 2018. © 2017 Wiley Periodicals, Inc.
Topics: Animals; Axons; Cell Movement; Glycosaminoglycans; Neurons; Synapses
PubMed: 28736980
DOI: 10.1002/dvdy.24555 -
Advances in Experimental Medicine and... 2021Ehlers-Danlos syndrome (EDS) is a genetically and clinically heterogeneous group of connective tissue disorders that typically present with skin hyperextensibility,...
Ehlers-Danlos syndrome (EDS) is a genetically and clinically heterogeneous group of connective tissue disorders that typically present with skin hyperextensibility, joint hypermobility, and tissue fragility. The major cause of EDS appears to be impaired biosynthesis and enzymatic modification of collagen. In this chapter, we discuss two types of EDS that are associated with proteoglycan abnormalities: spondylodysplastic EDS and musculocontractural EDS. Spondylodysplastic EDS is caused by pathogenic variants in B4GALT7 or B3GALT6, both of which encode key enzymes that initiate glycosaminoglycan synthesis. Musculocontractural EDS is caused by mutations in CHST14 or DSE, both of which encode enzymes responsible for the post-translational biosynthesis of dermatan sulfate. The clinical and molecular characteristics of both types of EDS are described in this chapter.
Topics: Collagen; Ehlers-Danlos Syndrome; Galactosyltransferases; Glycosaminoglycans; Humans; Mutation; Sulfotransferases
PubMed: 34807422
DOI: 10.1007/978-3-030-80614-9_10