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Glycobiology Jul 2022Chondroitin sulfate (CS) and dermatan sulfate (DS) containing GalNAc4,6-disulfate (GalNAc4S6S) were initially discovered in marine animals. Following the discovery,... (Review)
Review
Chondroitin sulfate (CS) and dermatan sulfate (DS) containing GalNAc4,6-disulfate (GalNAc4S6S) were initially discovered in marine animals. Following the discovery, these glycosaminoglycans have been found in various animals including human. In the biosynthesis of CS/DS containing GalNAc4S6S, 3 groups of sulfotransferases are involved; chondroitin 4-sulfotransferases (C4STs), dermatan 4-sulfotransferase-1 (D4ST-1), and GalNAc 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST). GalNAc4S-6ST and its products have been shown to play important roles in the abnormal pathological conditions such as central nervous system injury, cancer development, abnormal tissue fibrosis, development of osteoporosis, and infection with viruses or nematodes. CS/DS containing GalNAc4S6S has been shown to increase with the functional differentiation of mast cells, macrophages, and neutrophils. Genetic approaches using knockout or knockdown of GalNAc4S-6ST, blocking of the epitopes containing GalNAc4S6S by specific antibodies and chemical technology that enabled the synthesis of oligosaccharides with defined sulfation patterns, have been applied successfully to these investigations. These studies contributed significantly to the basic understanding of the functional roles of CS/DS containing GalNAc4S6S in various abnormal conditions and appear to provide promising clues to the development of possible measures to treat them.
Topics: Animals; Chondroitin Sulfates; Dermatan Sulfate; Glycosaminoglycans; Humans; Oligosaccharides; Sulfotransferases
PubMed: 35552694
DOI: 10.1093/glycob/cwac030 -
Frontiers in Immunology 2020
Topics: Animals; Glycosaminoglycans; Humans; Inflammation; Proteoglycans
PubMed: 33178227
DOI: 10.3389/fimmu.2020.595867 -
Genes Feb 2023Musculocontractural Ehlers-Danlos syndrome (mcEDS) is a subtype of EDS caused by mutations in the gene for carbohydrate sulfotransferase 14 () (mcEDS-) or dermatan... (Review)
Review
Musculocontractural Ehlers-Danlos syndrome (mcEDS) is a subtype of EDS caused by mutations in the gene for carbohydrate sulfotransferase 14 () (mcEDS-) or dermatan sulfate epimerase () (mcEDS-). These mutations induce loss of enzymatic activity in D4ST1 or DSE and disrupt dermatan sulfate (DS) biosynthesis. The depletion of DS causes the symptoms of mcEDS, such as multiple congenital malformations (e.g., adducted thumbs, clubfeet, and craniofacial characteristics) and progressive connective tissue fragility-related manifestations (e.g., recurrent dislocations, progressive talipes or spinal deformities, pneumothorax or pneumohemothorax, large subcutaneous hematomas, and/or diverticular perforation). Careful observations of patients and model animals are important to investigate pathophysiological mechanisms and therapies for the disorder. Some independent groups have investigated gene-deleted () and mice as models of mcEDS- and mcEDS-, respectively. These mouse models exhibit similar phenotypes to patients with mcEDS, such as suppressed growth and skin fragility with deformation of the collagen fibrils. Mouse models of mcEDS- also show thoracic kyphosis, hypotonia, and myopathy, which are typical complications of mcEDS. These findings suggest that the mouse models can be useful for research uncovering the pathophysiology of mcEDS and developing etiology-based therapy. In this review, we organize and compare the data of patients and model mice.
Topics: Animals; Mice; Dermatan Sulfate; Sulfotransferases; Ehlers-Danlos Syndrome; Skin; Extracellular Matrix
PubMed: 36833362
DOI: 10.3390/genes14020436 -
Arteriosclerosis, Thrombosis, and... Jun 2018The glycosaminoglycans (GAGs) heparan sulfate, dermatan sulfate, and heparin are important anticoagulants that inhibit clot formation through interactions with... (Review)
Review
The glycosaminoglycans (GAGs) heparan sulfate, dermatan sulfate, and heparin are important anticoagulants that inhibit clot formation through interactions with antithrombin and heparin cofactor II. Unfractionated heparin, low-molecular-weight heparin, and heparin-derived drugs are often the main treatments used clinically to handle coagulatory disorders. A wide range of proteins have been reported to bind and neutralize these GAGs to promote clot formation. Such neutralizing proteins are involved in a variety of other physiological processes, including inflammation, transport, and signaling. It is clear that these interactions are important for the control of normal coagulation and influence the efficacy of heparin and heparin-based therapeutics. In addition to neutralization, the anticoagulant activities of GAGs may also be regulated through reduced synthesis or by degradation. In this review, we describe GAG neutralization, the proteins involved, and the molecular processes that contribute to the regulation of anticoagulant GAG activity.
Topics: Animals; Anticoagulants; Binding Sites; Blood Coagulation; Dermatan Sulfate; Glycosaminoglycans; Heparin; Heparin Antagonists; Heparitin Sulfate; Humans; Protein Binding
PubMed: 29674476
DOI: 10.1161/ATVBAHA.118.311102 -
Molecular Genetics and Metabolism Jun 2020Glycosaminoglycans (GAGs) are negatively charged long linear (highly sulfated) polysaccharides consisting of repeating disaccharide units that are expressed on the... (Review)
Review
BACKGROUND
Glycosaminoglycans (GAGs) are negatively charged long linear (highly sulfated) polysaccharides consisting of repeating disaccharide units that are expressed on the surfaces of all nucleated cells. The expression of GAGs is required for embryogenesis, regulation of cell growth and proliferation, maintenance of tissue hydration, and interactions of the cells via receptors. Mucopolysaccharidoses (MPS) are caused by deficiency of specific lysosomal enzymes that result in the accumulation of GAGs in multiple tissues leading to organ dysfunction. Therefore, GAGs are important biomarkers for MPS. Without any treatment, patients with severe forms of MPS die within the first two decades of life.
SCOPE OF REVIEW
Accurate measurement of GAGs is important to understand the diagnosis and pathogenesis of MPS and to monitor therapeutic efficacy before, during, and after treatment of the disease. This review covers various qualitative and quantitative methods for measurement of GAGs, including dye specific, thin layer chromatography (TLC), capillary electrophoresis, high-performance liquid chromatography (HPLC), liquid chromatography-tandem mass spectrometry (LC-MS/MS), gas chromatography, ELISA, and automated high-throughput mass spectrometry. Major conclusion: There are several methods for GAG detection however, specific GAG detection in the various biological systems requires rapid, sensitive, specific, and cost-effective methods such as LC-MS/MS.
GENERAL SIGNIFICANCE
This review will describe different methods for GAG detection and analysis, including their advantages and limitation.
Topics: Biomarkers; Glycosaminoglycans; Humans; Mucopolysaccharidoses
PubMed: 32247585
DOI: 10.1016/j.ymgme.2020.03.004 -
Chemical Reviews Jul 2016Glycosaminoglycans (GAGs) as one major part of the glycocalyx are involved in many essential biological cell processes, as well as in many courses of diseases. Because... (Review)
Review
Glycosaminoglycans (GAGs) as one major part of the glycocalyx are involved in many essential biological cell processes, as well as in many courses of diseases. Because of the potential therapeutic application of GAG polymers, fragments, and also derivatives toward different diseases (e.g., heparin derivatives against Alzheimer's disease), there is a continual growing demand for new chemical syntheses, which suffice the high claim to stereoselectivity and chemoselectivity. This Review summarizes the progress of chemical syntheses of GAGs over the last 10 years. For each class of the glycosaminoglycans-hyaluronan (HA), heparan sulfate/heparin (HS/HP), chondroitin/dermatan sulfate (CS/DS), and keratan sulfate (KS)-mainly novel glycosylation strategies, elongation sequences, and protecting group patterns are discussed, but also (semi)automated syntheses, enzymatic approaches, and functionalizations of synthesized or isolated GAGs are considered.
Topics: Combinatorial Chemistry Techniques; Disaccharides; Glycosaminoglycans; Glycosylation; Monosaccharides
PubMed: 27410264
DOI: 10.1021/acs.chemrev.6b00010 -
The Journal of Histochemistry and... Feb 2021Glycosaminoglycans (GAGs) are heterogeneous, negatively charged, macromolecules that are found in animal tissues. Based on the form of component sugar, GAGs have been... (Review)
Review
Glycosaminoglycans (GAGs) are heterogeneous, negatively charged, macromolecules that are found in animal tissues. Based on the form of component sugar, GAGs have been categorized into four different families: heparin/heparan sulfate, chondroitin/dermatan sulfate, keratan sulfate, and hyaluronan. GAGs engage in biological pathway regulation through their interaction with protein ligands. Detailed structural information on GAG chains is required to further understanding of GAG-ligand interactions. However, polysaccharide sequencing has lagged behind protein and DNA sequencing due to the non-template-driven biosynthesis of glycans. In this review, we summarize recent progress in the analysis of GAG chains, specifically focusing on techniques related to mass spectroscopy (MS), including separation techniques coupled to MS, tandem MS, and bioinformatics software for MS spectrum interpretation. Progress in the use of other structural analysis tools, such as nuclear magnetic resonance (NMR) and hyphenated techniques, is included to provide a comprehensive perspective.
Topics: Computational Biology; Glycosaminoglycans; Humans; Mass Spectrometry; Nuclear Magnetic Resonance, Biomolecular; Proteoglycans; Software
PubMed: 32623943
DOI: 10.1369/0022155420937154 -
Glycoconjugate Journal Dec 2016Sulfatases that specifically catalyze the hydrolysis of the sulfate groups on chondroitin sulfate (CS)/dermatan sulfate (DS) poly- and oligosaccharides belong to the... (Review)
Review
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. Moreover, further studies will provide powerful tools for structural and functional studies of CS/DS as well as related applications. This article reviews the recent progress in CS/DS sulfatase research and is expected to initiate further research in this field.
Topics: Animals; Bacteria; Bacterial Proteins; Chondroitin Sulfates; Dermatan Sulfate; Humans; Structure-Activity Relationship; Sulfatases
PubMed: 27526113
DOI: 10.1007/s10719-016-9720-0 -
Frontiers in Cell and Developmental... 2020Chondroitin sulfate (CS) and dermatan sulfate (DS) are widely distributed on the cell surface and in the extracellular matrix in the form of proteoglycan, where they... (Review)
Review
Chondroitin sulfate (CS) and dermatan sulfate (DS) are widely distributed on the cell surface and in the extracellular matrix in the form of proteoglycan, where they participate in various biological processes. The diverse functions of CS/DS can be mainly attributed to their high structural variability. However, their structural complexity creates a big challenge for structural and functional studies of CS/DS. CS/DS-degrading enzymes with different specific activities are irreplaceable tools that could be used to solve this problem. Depending on the site of action, CS/DS-degrading enzymes can be classified as glycosidic bond-cleaving enzymes and sulfatases from animals and microorganisms. As discussed in this review, a few of the identified enzymes, particularly those from bacteria, have wildly applied to the basic studies and applications of CS/DS, such as disaccharide composition analysis, the preparation of bioactive oligosaccharides, oligosaccharide sequencing, and potential medical application, but these do not fulfill all of the needs in terms of the structural complexity of CS/DS.
PubMed: 33425887
DOI: 10.3389/fcell.2020.560442