-
The American Journal of Pathology Mar 2000Hurler disease resulting from a deficiency in alpha-L-iduronidase, which causes an accumulation of dermatan sulfate and heparan sulfate glycosaminoglycans, is... (Comparative Study)
Comparative Study
Hurler disease resulting from a deficiency in alpha-L-iduronidase, which causes an accumulation of dermatan sulfate and heparan sulfate glycosaminoglycans, is characterized by connective tissue and skeletal deformations, cardiomyopathy, cardiac valve defects, and progressive coronary artery stenosis. In this report, we present evidence that accumulation of dermatan sulfate but not heparan sulfate moieties is linked to impaired elastic fiber assembly that, in turn, contributes substantially to the development of the clinical phenotype in Hurler disease. Our data suggest that dermatan sulfate-bearing moieties bind to and cause functional inactivation of the 67-kd elastin-binding protein, a molecular chaperone for tropoelastin, which normally facilitates its secretion and assembly into elastic fibers. We demonstrate that, in contrast to normal skin fibroblasts and cells from Sanfilippo disease, which accumulate heparan sulfate, Hurler fibroblasts show reduced expression of elastin-binding protein and do not assemble elastic fibers, despite an adequate synthesis of tropoelastin and sufficient production of a microfibrillar scaffold of elastic fibers. Because cultured Hurler fibroblasts proliferate more quickly than their normal counterparts and the addition of exogenous insoluble elastin reduces their proliferation, we suggest that cell contacts with insoluble elastin play an important role in controlling their proliferation.
Topics: Adolescent; Cell Count; Cell Division; Cells, Cultured; Child; Child, Preschool; Coronary Vessels; Dermatan Sulfate; Elastic Tissue; Elastin; Female; Fetus; Fibroblasts; Fibronectins; Fluorescent Antibody Technique, Indirect; Heparitin Sulfate; Humans; Infant; Male; Mitral Valve; Mucopolysaccharidosis I; Mucopolysaccharidosis III; Receptors, Cell Surface; Skin; Tropoelastin
PubMed: 10702409
DOI: 10.1016/S0002-9440(10)64961-9 -
Blood Apr 2006Pregnancy is associated with hemostatic challenges that may lead to thrombosis. Heparin cofactor II (HCII) is a glycosaminoglycan-dependent thrombin inhibitor present in...
Pregnancy is associated with hemostatic challenges that may lead to thrombosis. Heparin cofactor II (HCII) is a glycosaminoglycan-dependent thrombin inhibitor present in both maternal and fetal plasma. HCII activity increases during pregnancy, and HCII levels are significantly decreased in women with severe pre-eclampsia. Dermatan sulfate (DS) specifically activates HCII and is abundant in the placenta, but the locations of DS and HCII in the placenta have not been determined. We present evidence that DS is the major anticoagulant glycosaminoglycan in the human placenta at term. DS isolated from human placenta contains disaccharides implicated in activation of HCII and has anticoagulant activity similar to that of mucosal DS. Immunohistochemical studies revealed that DS is associated with fetal blood vessels and stromal regions of placental villi but is notably absent from the syncytiotrophoblast cells in contact with the maternal circulation. HCII colocalizes with DS in the walls of fetal blood vessels and is also present in syncytiotrophoblast cells. Our data suggest that DS is in a position to activate HCII in the fetal blood vessels or in the stroma of placental villi after injury to the syncytiotrophoblast layer and thereby inhibit fibrin generation in the placenta.
Topics: Anticoagulants; Dermatan Sulfate; Female; Glycosaminoglycans; Heparin Cofactor II; Humans; Immunohistochemistry; Placenta; Pre-Eclampsia; Pregnancy; Substrate Specificity
PubMed: 16339402
DOI: 10.1182/blood-2005-09-3755 -
Dermatan sulfate-chondroitin sulfate copolymers from ambilical cord. Isolation and characterization.Journal of Biochemistry Sep 1976Dermatan sulfate-chondroitin sulfate copolymers have been isolated from human umbilical cord as a major galactosaminoglycan component of this tissue. The...
Dermatan sulfate-chondroitin sulfate copolymers have been isolated from human umbilical cord as a major galactosaminoglycan component of this tissue. The galactosaminoglycan fraction was obtained from this tissue by papain [EC 3.4.22.2] digestion followed by precipitation with cetylpyridinium chloride in a yield of 700 mg per 100 g of dry tissue. Ethanol fractionation resolved 4-5 subfractions differing in relative content of L-iduronic acid and D-glucuronic acid. No galactosaminoglycan containing either solely L-iduronic acid or D-glucuronic acid was obtained. The copolymeric structure of the material in each subfraction was demonstrated by analysis of oligosaccharide fragments obtained by chondroitinase-AC [EC 4.2.2.5] digestion. All the polymers contained repeating disaccharide units, D-glucuronosyl-N-acetylgalactosamine, D-glucuronosyl-N-acetylgalactosamine 4-sulfate, D-glucuronosyl-N-acetyl-galactosamine 6-sulfate, and L-iduronosyl-N-acetylgalactosamine 4-sulfate, of which D-glucuronosyl-N-acetylgalactosamine 6-sulfate and L-iduronosyl-N-acetylgalactosamine 4-sulfate were predominant. Both iduronic acid- and glucuronic acid-containing units were arranged in clusters. The presence of a considerable amount of nonsulfated disaccharide units was noted. The copolymers show extensive polydispersity in electrophoresis on cellulose acetate and gel chromatography on Sephadex G-200.
Topics: Amino Acids; Chondroitin; Chondroitin Sulfates; Chondroitinases and Chondroitin Lyases; Dermatan Sulfate; Glucuronates; Glycosaminoglycans; Humans; Iduronic Acid; Oligosaccharides; Polymers; Umbilical Cord; Uronic Acids
PubMed: 977551
DOI: 10.1093/oxfordjournals.jbchem.a131306 -
Cell Reports Mar 2022Sulfs represent a class of unconventional sulfatases which provide an original post-synthetic regulatory mechanism for heparan sulfate polysaccharides and are involved...
Sulfs represent a class of unconventional sulfatases which provide an original post-synthetic regulatory mechanism for heparan sulfate polysaccharides and are involved in multiple physiopathological processes, including cancer. However, Sulfs remain poorly characterized enzymes, with major discrepancies regarding their in vivo functions. Here we show that human Sulf-2 (HSulf-2) harbors a chondroitin/dermatan sulfate glycosaminoglycan (GAG) chain, attached to the enzyme substrate-binding domain. We demonstrate that this GAG chain affects enzyme/substrate recognition and tunes HSulf-2 activity in vitro and in vivo. In addition, we show that mammalian hyaluronidase acts as a promoter of HSulf-2 activity by digesting its GAG chain. In conclusion, our results highlight HSulf-2 as a proteoglycan-related enzyme and its GAG chain as a critical non-catalytic modulator of the enzyme activity. These findings contribute to clarifying the conflicting data on the activities of the Sulfs.
Topics: Animals; Dermatan Sulfate; Heparitin Sulfate; Humans; Mammals; Protein Binding; Sulfatases; Sulfotransferases
PubMed: 35294879
DOI: 10.1016/j.celrep.2022.110516 -
Glycoconjugate Journal Nov 2014Glycosaminoglycans (GAGs) have numerous applications in the fields of pharmaceuticals, cosmetics, nutraceuticals, and foods. GAGs are also critically important in the...
Glycosaminoglycans (GAGs) have numerous applications in the fields of pharmaceuticals, cosmetics, nutraceuticals, and foods. GAGs are also critically important in the developmental biology of all multicellular animals. GAGs were isolated from chicken egg components including yolk, thick egg white, thin egg white, membrane, calcified shell matrix supernatant, and shell matrix deposit. Disaccharide compositional analysis was performed using ultra high-performance liquid chromatography-mass spectrometry. The results of these analyses showed that all four families of GAGs were detected in all egg components. Keratan sulfate was found in egg whites (thick and thin) and shell matrix (calcified shell matrix supernatant and deposit) with high level. Chondroitin sulfates were much more plentiful in both shell matrix components and membrane. Hyaluronan was plentiful in both shell matrix components and membrane, but was only present in a trace of quantities in the yolk. Heparan sulfate was plentiful in the shell matrix deposit but was present in a trace of quantities in the egg content components (yolk, thick and thin egg whites). Most of the chondroitin and heparan sulfate disaccharides were present in the GAGs found in chicken eggs with the exception of chondroitin and heparan sulfate 2,6-disulfated disaccharides. Both CS and HS in the shell matrix deposit contained the most diverse chondroitin and heparan sulfate disaccharide compositions. Eggs might provide a potential new source of GAGs.
Topics: Animals; Azetidines; Chickens; Chondroitin Sulfates; Dermatan Sulfate; Disaccharides; Glycosaminoglycans; Hyaluronic Acid; Keratan Sulfate; Nitriles; Ovum
PubMed: 25218438
DOI: 10.1007/s10719-014-9557-3 -
The Journal of Biological Chemistry Apr 1999A partial-length human cDNA with a predicted amino acid sequence homologous to a previously described heparan sulfate iduronyl 2-sulfotransferase (Kobayashi, M.,...
A partial-length human cDNA with a predicted amino acid sequence homologous to a previously described heparan sulfate iduronyl 2-sulfotransferase (Kobayashi, M., Habuchi, H., Yoneda, M., Habuchi, O., and Kimata, K. (1997) J. Biol. Chem. 272, 13980-13985) was obtained by searching the expressed sequence-tagged data bank. Northern blot analysis was performed using this homologous cDNA as a probe, which demonstrated ubiquitous expression of messages of 5.1 and 2.0 kilobases in a number of human tissues and in several human cancer cell lines. Since the human lymphoma Raji cell line had the highest level of expression, it was used to isolate a full-length cDNA clone. The full-length cDNA was found to contain an open reading frame that predicted a type II transmembrane protein composed of 406 amino acid residues. The cDNA in a baculovirus expression vector was expressed in Sf9 insect cells, and cell extracts were then incubated together with 3'-phosphoadenosine 5'-phospho[35S]sulfate and potential glycosaminoglycan acceptors. This demonstrated substantial sulfotransferase activity with dermatan sulfate, a small degree of activity with chondroitin sulfate, but no sulfotransferase activity with desulfated N-resulfated heparin. Analysis of [35S]sulfate-labeled disaccharide products of chondroitin ABC, chondroitin AC, and chondroitin B lyase treatment demonstrated that the enzyme only transferred sulfate to the 2-position of uronyl residues, which were preponderantly iduronyl residues in dermatan sulfate, but some lesser transfer to glucuronyl residues of chondroitin sulfate.
Topics: Amino Acid Sequence; Animals; Baculoviridae; Base Sequence; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Cloning, Molecular; DNA, Complementary; Dermatan Sulfate; Expressed Sequence Tags; Glucuronates; Glucuronic Acid; Humans; Iduronic Acid; Molecular Sequence Data; Spodoptera; Sulfotransferases; Tumor Cells, Cultured
PubMed: 10187838
DOI: 10.1074/jbc.274.15.10474 -
Laboratory Investigation; a Journal of... Sep 2001Mucopolysaccharidosis (MPS) Type VI (Maroteaux-Lamy Disease) is the lysosomal storage disease characterized by deficient arylsulfatase B activity and the resultant...
Articular chondrocytes from animals with a dermatan sulfate storage disease undergo a high rate of apoptosis and release nitric oxide and inflammatory cytokines: a possible mechanism underlying degenerative joint disease in the mucopolysaccharidoses.
Mucopolysaccharidosis (MPS) Type VI (Maroteaux-Lamy Disease) is the lysosomal storage disease characterized by deficient arylsulfatase B activity and the resultant accumulation of dermatan sulfate-containing glycosaminoglycans (GAGs). A major feature of this and other MPS disorders is abnormal cartilage and bone development leading to short stature, dysostosis multiplex, and degenerative joint disease. To investigate the underlying cause(s) of degenerative joint disease in the MPS disorders, articular cartilage and cultured articular chondrocytes were examined from rats and cats with MPS VI. An age-progressive increase in the number of apoptotic chondrocytes was identified in the MPS animals by terminal transferase nick-end translation (TUNEL) staining and by immunohistochemical staining with anti-poly (ADP-ribose) polymerase (PARP) antibodies. Articular chondrocytes grown from these animals also released more nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) into the culture media than did control chondrocytes. Notably, dermatan sulfate, the GAG that accumulates in MPS VI cells, induced NO release from normal chondrocytes, suggesting that GAG accumulation was responsible, in part, for the enhanced cell death in the MPS cells. Coculture of normal chondrocytes with MPS VI cells reduced the amount of NO release, presumably because of the release of arylsulfatase B by the normal cells and reuptake by the mutant cells. As a result of the enhanced chondrocyte death, marked proteoglycan and collagen depletion was observed in the MPS articular cartilage matrix. These results demonstrate that MPS VI articular chondrocytes undergo cell death at a higher rate than normal cells, because of either increased levels of dermatan sulfate and/or the presence of inflammatory cytokines in the MPS joints. In turn, this leads to abnormal cartilage matrix homeostasis in the MPS individuals, which further exacerbates the joint deformities characteristic of these disorders.
Topics: Animals; Apoptosis; Bone Matrix; Cartilage, Articular; Cats; Chondrocytes; Coculture Techniques; Cytokines; Dermatan Sulfate; Inflammation Mediators; Joint Diseases; Lipopolysaccharides; Mucopolysaccharidosis VI; Nitric Oxide; Rats; Tumor Necrosis Factor-alpha
PubMed: 11555679
DOI: 10.1038/labinvest.3780345 -
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 -
The Journal of Biological Chemistry Mar 1987Dermatan sulfate proteoglycans were isolated from adult bovine sclera and adult bovine articular cartilage. Their immunological relationships were studied by... (Comparative Study)
Comparative Study
Dermatan sulfate proteoglycans were isolated from adult bovine sclera and adult bovine articular cartilage. Their immunological relationships were studied by enzyme-linked immunosorbent assays using polyclonal antibodies raised against the large and small dermatan sulfate proteoglycans from sclera and a polyclonal and monoclonal antibody directed against the small dermatan sulfate proteoglycans from cartilage. The small dermatan sulfate proteoglycans from sclera and cartilage displayed immunological cross-reactivity while there was no convincing evidence of shared epitope(s) with the larger dermatan sulfate proteoglycans, nor did these larger proteoglycans share any common epitopes with each other. A hyaluronic acid binding region was detected immunologically on the larger scleral dermatan sulfate proteoglycan but was absent from the larger dermatan sulfate proteoglycan of cartilage and both the small dermatan sulfate proteoglycans. These antibodies were used in immunofluorescence microscopy to localize the scleral proteoglycans and molecules containing these epitopes in the eye. The large scleral dermatan sulfate proteoglycan was restricted to sclera while molecules related to the small scleral and cartilage proteoglycans were found in the sclera, anterior uveal tract, iris, and cornea. Amino acid sequencing of the amino-terminal regions of the core proteins of the small dermatan sulfate proteoglycans from sclera and articular cartilage showed that all the first 14 amino acids analyzed were identical and the same as reported earlier for the small bovine skin and tendon dermatan sulfate proteoglycans. These studies demonstrate that the larger dermatan sulfate proteoglycans of sclera and cartilage are chemically unrelated to each other and to the smaller dermatan sulfate proteoglycans isolated from these tissues. The latter have closely related core proteins and probably represent a molecule with a widespread distribution in which the degree of epimerization of glucuronic acid and iduronic acid varies between tissues.
Topics: Amino Acid Sequence; Animals; Antibodies; Antibodies, Monoclonal; Antigen-Antibody Complex; Cartilage, Articular; Cattle; Chondroitin; Chondroitin Sulfate Proteoglycans; Cornea; Dermatan Sulfate; Enzyme-Linked Immunosorbent Assay; Iris; Organ Specificity; Proteoglycans; Sclera
PubMed: 3818667
DOI: No ID Found -
The Journal of International Medical... Jun 2019To test the antifibrotic effect of dermatan sulphate in a bleomycin-induced mouse model of pulmonary fibrosis.
OBJECTIVE
To test the antifibrotic effect of dermatan sulphate in a bleomycin-induced mouse model of pulmonary fibrosis.
METHODS
C57 mice were randomly divided into four experimental groups: saline-treated control group, bleomycin-induced fibrosis group, prednisolone acetate group and dermatan sulphate group. Lungs were assessed using the lung index, and the extent of interstitial fibrosis was graded using histopathological observation of haematoxylin & eosin-stained lung tissue. Lung tissue hydroxyproline levels and blood fibrinogen levels were measured using a hydroxyproline colorimetric kit and the Clauss fibrinogen assay, respectively. Tissue-type plasminogen activator (tPA) was measured using a chromogenic tPA assay kit.
RESULTS
Lung index values were significantly lower in the dermatan sulphate group versus the fibrosis group. Histopathological analyses revealed that dermatan sulphate treatment ameliorated the increased inflammatory cell infiltration, and attenuated the reduction in interstitial thickening, associated with bleomycin-induced fibrosis. Hydroxyproline and fibrinogen levels were decreased in the dermatan sulphate group versus the fibrosis model group. Dermatan sulphate treatment was associated with increased tPA levels versus controls and the fibrosis group.
CONCLUSIONS
Damage associated with bleomycin-induced pulmonary fibrosis was alleviated by dermatan sulphate.
Topics: Animals; Antibiotics, Antineoplastic; Anticoagulants; Bleomycin; Dermatan Sulfate; Disease Models, Animal; Female; Hydroxyproline; Male; Mice; Mice, Inbred C57BL; Pulmonary Fibrosis
PubMed: 31006321
DOI: 10.1177/0300060519842048