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Amino Acids Jul 2011Chondroitin sulfate (CS) and dermatan sulfate (DS) are special types of glycosaminoglycan (GAG) oligosaccharides able to regulate vital biological functions that depend... (Review)
Review
Chondroitin sulfate (CS) and dermatan sulfate (DS) are special types of glycosaminoglycan (GAG) oligosaccharides able to regulate vital biological functions that depend on precise motifs of their constituent hexose sequences and the extent and location of their sulfation. As a result, the need for better understanding of CS/DS biological role called for the elaboration and application of straightforward strategies for their composition and structure elucidation. Due to its high sensitivity, reproducibility, and the possibility to rapidly generate data on fine CS/DS structure determinants, mass spectrometry (MS) based on either electrospray ionization (ESI) or matrix-assisted laser desorption/ionization (MALDI) brought a major progress in the field. Here, modern developments in MS of CS/DS GAGs are gathered in a critical review covering the past 5 years. The first section is dedicated to protocols for CS/DS extraction from parent proteoglycan, digestion, and purification that are among critical prerequisites of a successful MS experiment. The second part highlights several MALDI MS aspects, the requirements, and applications of this ionization method to CS/DS investigation. An ample chapter is devoted to ESI MS strategies, which employ either capillary- or advanced chip-based sample infusion in combination with multistage MS (MS(n)) using either collision-induced (CID) or electron detachment dissociation (EDD). At last, the potential of two versatile separation techniques, capillary electrophoresis (CE), and liquid chromatography (LC) in off- and/or on-line coupling with ESI MS and MS(n), is discussed, alongside an assessment of particular buffer/solvent conditions and instrumental parameters required for CS/DS mixture separation followed by on-line mass analysis of individual components.
Topics: Animals; Carbohydrate Sequence; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Dermatan Sulfate; Electrophoresis, Capillary; Glycosaminoglycans; Humans; Mass Spectrometry; Proteoglycans; Sequence Analysis
PubMed: 20632047
DOI: 10.1007/s00726-010-0682-4 -
The Journal of Toxicological Sciences 2023Cadmium is an environmental pollutant and a risk factor for atherosclerosis. In the atherosclerotic intima, dermatan sulfate chains accelerate accumulation and oxidation...
Cadmium is an environmental pollutant and a risk factor for atherosclerosis. In the atherosclerotic intima, dermatan sulfate chains accelerate accumulation and oxidation of LDL cholesterol. The major type of dermatan sulfate proteoglycan that is synthesized by vascular endothelial cells is biglycan. In the present study, we analyzed the effect of cadmium on the biglycan synthesis using cultured bovine aortic endothelial cells. Cadmium did not induce biglycan mRNA and core protein expression; however, it elongated the chondroitin/dermatan sulfate chains of biglycan. Among elongation enzymes of the chondroitin/dermatan sulfate chain, chondroitin sulfate synthase 1 (CHSY1) mRNA and protein expression were dose- and time-dependently upregulated by cadmium depending on protein kinase Cα. This finding suggests that CHSY1-dependent elongation of chondroitin/dermatan sulfate chains of biglycan may exacerbate cadmium-induced atherosclerosis.
Topics: Animals; Cattle; Chondroitin Sulfates; Biglycan; Dermatan Sulfate; Cadmium; Endothelial Cells; RNA, Messenger; Protein Kinases; Cells, Cultured
PubMed: 37532579
DOI: 10.2131/jts.48.457 -
Acta Biomaterialia Jan 2024Fibrillar collagens and glycosaminoglycans (GAGs) are structural biomolecules that are natively abundant to the extracellular matrix (ECM). Prior studies have quantified...
Fibrillar collagens and glycosaminoglycans (GAGs) are structural biomolecules that are natively abundant to the extracellular matrix (ECM). Prior studies have quantified the effects of GAGs on the bulk mechanical properties of the ECM. However, there remains a lack of experimental studies on how GAGs alter other biophysical properties of the ECM, including ones that operate at the length scales of individual cells such as mass transport efficiency and matrix microstructure. This study focuses on the GAG molecules chondroitin sulfate (CS), dermatan sulfate (DS), and hyaluronic acid (HA). CS and DS are stereoisomers while HA is the only non-sulfated GAG. We characterized and decoupled the effects of these GAG molecules on the stiffness, transport, and matrix microarchitecture properties of type I collagen hydrogels using mechanical indentation testing, microfluidics, and confocal reflectance imaging, respectively. We complement these biophysical measurements with turbidity assays to profile collagen aggregate formation. Surprisingly, only HA enhanced the ECM indentation modulus, while all three GAGs had no effect on hydraulic permeability. Strikingly, we show that CS, DS, and HA differentially regulate the matrix microarchitecture of hydrogels due to their alterations to the kinetics of collagen self-assembly. In addition to providing information on how GAGs define key physical properties of the ECM, this work shows new ways in which stiffness measurements, microfluidics, microscopy, and turbidity kinetics can be used complementarily to reveal details of collagen self-assembly and structure. STATEMENT OF SIGNIFICANCE: Collagen and glycosaminoglycans (GAGs) are integral to the structure, function, and bioactivity of the extracellular matrix (ECM). Despite widespread interest in collagen-GAG composite hydrogels, there is a lack of quantitative understanding of how different GAGs alter the biophysical properties of the ECM across tissue, cellular, and subcellular length scales. Here we show using mechanical, microfluidic, microscopy, and analytical methods and measurements that the GAG molecules chondroitin sulfate, dermatan sulfate, and hyaluronic acid differentially regulate the mechanical, transport, and microstructural properties of hydrogels due to their alterations to the kinetics of collagen self-assembly. As such, these results will inform improved design and utilization of collagen-based scaffolds of tailored composition, mechanical properties, molecular availability due to mass transport, and microarchitecture.
Topics: Chondroitin Sulfates; Hyaluronic Acid; Dermatan Sulfate; Hydrogels; Glycosaminoglycans; Collagen; Extracellular Matrix
PubMed: 38101556
DOI: 10.1016/j.actbio.2023.12.018 -
Marine Drugs Oct 2022Acute and chronic dermatological injuries need rapid tissue repair due to the susceptibility to infections. To effectively promote cutaneous wound recovery, it is...
Acute and chronic dermatological injuries need rapid tissue repair due to the susceptibility to infections. To effectively promote cutaneous wound recovery, it is essential to develop safe, low-cost, and affordable regenerative tools. Therefore, we aimed to identify the biological mechanisms involved in the wound healing properties of the glycosaminoglycan dermatan sulfate (DS), obtained from ascidian , a marine invertebrate, which in preliminary work from our group showed no toxicity and promoted a remarkable fibroblast proliferation and migration. In this study, 2,4-DS (50 µg/mL)-treated and control groups had the relative gene expression of 84 genes participating in the healing pathway evaluated. The results showed that 57% of the genes were overexpressed during treatment, 16% were underexpressed, and 9.52% were not detected. In silico analysis of metabolic interactions exhibited overexpression of genes related to: extracellular matrix organization, hemostasis, secretion of inflammatory mediators, and regulation of insulin-like growth factor transport and uptake. Furthermore, in C57BL/6 mice subjected to experimental wounds treated with 0.25% 2,4-DS, the histological parameters demonstrated a great capacity for vascular recovery. Additionally, this study confirmed that DS is a potent inducer of wound-healing cellular pathways and a promoter of neovascularization, being a natural ally in the tissue regeneration strategy.
Topics: Animals; Mice; Dermatan Sulfate; Mice, Inbred C57BL; Urochordata; Wound Healing; Natural Resources
PubMed: 36354999
DOI: 10.3390/md20110676 -
PloS One 2017Transglutaminase 2 (TG2) is a multifunctional protein that is primarily engaged in cell adhesion/signaling or shows Ca2+-dependent transglutaminase activity in the...
Transglutaminase 2 (TG2) is a multifunctional protein that is primarily engaged in cell adhesion/signaling or shows Ca2+-dependent transglutaminase activity in the extracellular space of tissues. This latter action leads to the cross-linking of the extracellular matrix (ECM) proteins. The enhanced extracellular expression of TG2 is associated with processes such as wound healing, fibrosis or vascular remodeling that are also characterized by a high deposition of dermatan sulfate (DS) proteoglycans in the ECM. However, it is unknown whether DS may bind to TG2 or affect its function. Using the plasmon surface resonance method, we showed that DS chains, especially those of biglycan, are good binding partners for TG2. The interaction has some requirements as to the DS structure. The competitive effect of heparin on DS binding to TG2 suggests that both glycosaminoglycans occupy the same binding site(s) on the protein molecule. An occurrence of the DS-TG2 interaction was confirmed by the co-immunoprecipitation of this protein with native decorin that is a DS-bearing proteoglycan rather than with the decorin core protein. Moreover, in vivo DS is responsible for both TG2 binding and the regulation of the location of this protein in the ECM as can be suggested from an increased extraction of TG2 from the human fascia only when an enzymatic degradation of the tissue DS was conducted in the presence of the anti-collagen type I antiserum. In addition, DS with a low affinity for TG2 exerted an inhibitory effect on the protein transamidating activity most probably via the control of the accessibility of a substrate. Our data show that DS can affect several aspects of TG2 biology in both physiological and pathological conditions.
Topics: Animals; Cell Line; Chromatography, High Pressure Liquid; Dermatan Sulfate; GTP-Binding Proteins; Humans; Immunoprecipitation; Protein Binding; Protein Glutamine gamma Glutamyltransferase 2; Surface Plasmon Resonance; Swine; Transglutaminases
PubMed: 28199387
DOI: 10.1371/journal.pone.0172263 -
TheScientificWorldJournal Jul 2005
Review
Topics: Animals; Atherosclerosis; Chondroitin Sulfates; Dermatan Sulfate; Extracellular Matrix; Glycosaminoglycans; Humans; Models, Cardiovascular; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Proteoglycans
PubMed: 16075147
DOI: 10.1100/tsw.2005.69 -
PharmacoEconomics Jan 2001In a recent clinical trial, dermatan sulfate was found to be more effective than unfractionated heparin (UFH), but equally well tolerated, for the prevention of deep... (Comparative Study)
Comparative Study
BACKGROUND
In a recent clinical trial, dermatan sulfate was found to be more effective than unfractionated heparin (UFH), but equally well tolerated, for the prevention of deep vein thrombosis (DVT) after major surgery for cancer.
OBJECTIVE
To perform a cost-effectiveness analysis of dermatan sulfate versus UFH in this clinical setting.
DESIGN AND SETTING
This was a retrospective economic analysis using data from a randomised clinical trial, and was performed from the hospital perspective.
METHODS
Clinical event rates were extrapolated from the observed venographic DVT rates, using appropriate assumptions from the scientific literature. The economic effects of switching DVT prophylaxis from UFH to dermatan sulfate and the potential lives saved were assessed by a predictive decision model.
RESULTS
The per patient cost, including the burden of residual thromboembolic events and major bleeding complications, was estimated to be 154 euros (EUR) for dermatan sulfate and EUR185 for UFH (1998 values). With reference to a potential target population of 60,000 patients/year undergoing surgery for cancer in Italy, the total prophylaxis-associated cost was EUR9,258,000 for dermatan sulfate and EUR11,096,000 for UFH, whereas the potential deaths from prophylaxis failure were 204 and 392, respectively. This represented a saving of EUR1,838,000 and 188 potential lives per year with the dermatan sulfate option. The final costs and effects were mainly sensitive to variations in the rates of DVT and pulmonary embolism, and to the possible need for 1 extra day of hospitalisation because of the earlier preoperative initiation of dermatan sulfate prophylaxis.
CONCLUSION
Dermatan sulfate is more cost effective than UFH for the prevention of postoperative venous thromboembolism in patients with cancer. If the hospital stay needs to be prolonged, then the dermatan sulfate option may involve a small additional cost (EUR47) per potential life saved.
Topics: Adult; Anticoagulants; Cost-Benefit Analysis; Decision Trees; Dermatan Sulfate; Health Care Costs; Heparin; Humans; Multicenter Studies as Topic; Neoplasms; Postoperative Complications; Randomized Controlled Trials as Topic; Retrospective Studies; Venous Thrombosis
PubMed: 11252546
DOI: 10.2165/00019053-200119010-00004 -
The Journal of Biological Chemistry Jul 2016We previously reported that the xyloside 2-(6-hydroxynaphthyl) β-d-xylopyranoside (XylNapOH), in contrast to 2-naphthyl β-d-xylopyranoside (XylNap), specifically...
We previously reported that the xyloside 2-(6-hydroxynaphthyl) β-d-xylopyranoside (XylNapOH), in contrast to 2-naphthyl β-d-xylopyranoside (XylNap), specifically reduces tumor growth both in vitro and in vivo Although there are indications that this could be mediated by the xyloside-primed glycosaminoglycans (GAGs) and that these differ in composition depending on xyloside and cell type, detailed knowledge regarding a structure-function relationship is lacking. In this study we isolated XylNapOH- and XylNap-primed GAGs from a breast carcinoma cell line, HCC70, and a breast fibroblast cell line, CCD-1095Sk, and demonstrated that both XylNapOH- and XylNap-primed chondroitin sulfate/dermatan sulfate GAGs derived from HCC70 cells had a cytotoxic effect on HCC70 cells and CCD-1095Sk cells. The cytotoxic effect appeared to be mediated by induction of apoptosis and was inhibited in a concentration-dependent manner by the XylNap-primed heparan sulfate GAGs. In contrast, neither the chondroitin sulfate/dermatan sulfate nor the heparan sulfate derived from CCD-1095Sk cells primed on XylNapOH or XylNap had any effect on the growth of HCC70 cells or CCD-105Sk cells. These observations were related to the disaccharide composition of the XylNapOH- and XylNap-primed GAGs, which differed between the two cell lines but was similar when the GAGs were derived from the same cell line. To our knowledge this is the first report on cytotoxic effects mediated by chondroitin sulfate/dermatan sulfate.
Topics: Apoptosis; Cell Division; Cell Line, Tumor; Chondroitin Sulfates; Dermatan Sulfate; Disaccharides; Female; Glycosides; Humans; In Vitro Techniques
PubMed: 27226567
DOI: 10.1074/jbc.M116.716829 -
The Journal of Biological Chemistry Oct 2019Chemokines play diverse roles in human pathophysiology, ranging from trafficking leukocytes and immunosurveillance to the regulation of metabolism and neural function....
Chemokines play diverse roles in human pathophysiology, ranging from trafficking leukocytes and immunosurveillance to the regulation of metabolism and neural function. Chemokine function is intimately coupled to binding tissue glycosaminoglycans (GAGs), heparan sulfate (HS), chondroitin sulfate (CS), and dermatan sulfate (DS). Currently, very little is known about how the structural features and sequences of a given chemokine, the structure and sulfation pattern of a given GAG, and structural differences among GAGs and among chemokines impact binding interactions. In this study, we used solution NMR spectroscopy to characterize the binding interactions of two related neutrophil-activating chemokines, CXCL1 and CXCL5, with HS, CS, and DS. For both chemokines, the dimer bound all three GAGs with higher affinity than did the monomer, and affinities of the chemokines for CS and DS were lower than for HS. NMR-based structural models reveal diverse binding geometries and show that the binding surfaces for each of the three GAGs were different between the two chemokines. However, a given chemokine had similar binding interactions with CS and DS that were different from HS. Considering the fact that CXCL1 and CXCL5 activate the same CXCR2 receptor, we conclude that GAG interactions play a role in determining the nature of chemokine gradients, levels of free chemokine available for receptor activation, how chemokines bind their receptors, and that differences in these interactions determine chemokine-specific function.
Topics: Chemokines; Chondroitin Sulfates; Dermatan Sulfate; Heparitin Sulfate; Models, Molecular; Protein Binding; Proton Magnetic Resonance Spectroscopy
PubMed: 31455633
DOI: 10.1074/jbc.RA119.009879 -
Advances in Pharmacology (San Diego,... 2006
Review
Topics: Chondroitin Sulfates; Chromatography, Gel; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Dermatan Sulfate; Electrophoresis; Enzyme-Linked Immunosorbent Assay; Immunohistochemistry
PubMed: 17239765
DOI: 10.1016/S1054-3589(05)53007-2