scholarly journals Identification of keratan sulfate disaccharide at C-3 position of glucuronate of chondroitin sulfate from Mactra chinensis

2016 ◽  
Vol 473 (22) ◽  
pp. 4145-4158 ◽  
Author(s):  
Kyohei Higashi ◽  
Keita Takeda ◽  
Ann Mukuno ◽  
Yusuke Okamoto ◽  
Sayaka Masuko ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Chondroitin Sulfate ◽  
Hippocampal Neurons ◽  
Uronic Acid ◽  
Dermatan Sulfate ◽  
Biological Activities ◽  
Keratan Sulfate ◽  
Structural Variations ◽  
Low Concentrations ◽  
Mactra Chinensis

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 CS-E derived from a clam, Mactra chinensis. KS disaccharide [d-GlcNAc6S-(1→3)-β-d-Gal-(1→] was attached to the C-3 position of GlcA, and consecutive KS-branched disaccharide sequences were found in a CS chain. KS-branched polysaccharides clearly exhibited resistance to degradation by chondroitinase ABC or ACII (at low concentrations) compared with typical CS structures. Furthermore, KS-branched polysaccharides stimulated neurite outgrowth of hippocampal neurons. These results strongly suggest that M. chinensis is a rich source of KS-branched CS, and it has important biological activities.

scholarly journals Cytotoxic and Anti- Inflammatory Activities of Glycosaminoglycans (GAGs) from Selected Sea Food Waste Extract on Cell Lines

2020 ◽  
Vol 981 ◽  
pp. 258-264
Author(s):  
Nurul Haida Idrus ◽  
Nina Suhaity Azmi ◽  
Che Nur Mazadillina Che Zahari ◽  
Solachuddin Jauhari Arief Ichwan
Keyword(s):  
Dermatan Sulfate ◽  
Biological Activities ◽  
Keratan Sulfate ◽  
Sea Bass ◽  
Raw Material ◽  
No Production ◽  
Dependent Manner ◽  
Alternative Source ◽  
Anti Inflammatory ◽  
Dose Dependent

Glycosaminoglycans (GAGs) are long unbranched polysaccharide that composed of repeating disaccharide units. They are classified into heparan sulfate (HS), heparin, chondroitin sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS) and hyaluronic acid (HA). During the last decade, demand of GAGs were getting increased due to their potential uses. Vertebrate animal, commonly cartilaginous mammalian tissue, were potential producer of GAGs and have the higher number of biological activities extracted from sea bass waste. Sea bass waste from Lates calcarifer was used as the raw material to extract crude GAGs. Different part of sea bass waste such as, gills, viscera and air bladders were used. The higher content of crude GAGs in sea bass waste was used in cytotoxic and inflammatory study. Different concentration of extract GAGs from gills were used ranging between 0.16-20 mg/mL. GAGs from sea bass waste (gills) showed dose-dependent cytotoxic activity towards MCF-7 cell line in lower concentration. Meanwhile, for anti-inflammatory study GAGs from sea bass waste (gills) showed dose-dependent manner and also reduce NO production in LPS-stimulated cells. This research study concluded that, GAGs from sea bass waste are the alternative source that can be used for cancer and inflammation study.

HIGH CONCENTRATIONS OF HEPARIN ARE MORE INHIBITORY TO PLATE- AGGREGATION IN-VITRO THAN ARE LOW MOLECULAR WEIGHT HEPARINS AND HEPARINOIDS AT THE SAME CONCENTRATION

1987 ◽  
Author(s):  
H Messmore ◽  
B Griffin ◽  
J Seghatchian ◽  
E Coyne
Keyword(s):  
Molecular Weight ◽  
Heparan Sulfate ◽  
Dermatan Sulfate ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Low Molecular Weight ◽  
Low Concentrations ◽  
High Concentrations ◽  
Induced Aggregation

Other investigators have shown that heparin in the usual therapeutic range (0.1-0.5 units/ml) has an enhancing effect on ADP aggregation and an inhibitory effect on collagen and thrombin induced aggregation. The effects of low molecular weight heparin (LMWH)and heparinoids (dermatan sulfate, heparan sulfate) on platelet aggregation have not been as extensivelystudied. We have utilized citrated platelet rich plasma (3.2%citrate-whole blood 1:9) drawn in plastic and adjusted to a final platelet count of 250,000/ul. A Bio-Data 4 channgl aggregometer was utilized with constantstirring at 37 C. The reaction was allowed to run for 20 minutes. Platelet rich plasma was supplemented 1:9 with saline or heparin and various agonists were then added ifno aggregation occurred. ADP, collagen, thrombin, ristocetin and serum from patients with heparin inudced thrombocytopenia (HIT) were utilized as agonists. Heparin was substituted at concentrations of 0.1 to 500 units per ml and various LMWH and heparinoids were substituted in equivalent anti-Xa or gravimetric concentrations. At low concentrations no inhibitory effect on any ofthe agonists was observed with any of the heparins or heparinoids. At concentrations of heparin of 100 u/ml or greater, all agonists were inhibited. At equivalent concentrations of five different LMWH (Cy 216, Cy 222, Pk 10169, Kabi 2165 and pentasaccharide) inhibition did notoccur at all or at very high concentions only. Dermatan sulfate and heparan sulfate inhibited only at high concentrations. HIT serum could not aggregate platelets with dermatan sulfate or pentasaccharide atany concentrations, but it was a good agonist with the other heparins and heparinoids.

scholarly journals An Overview of in vivo Functions of Chondroitin Sulfate and Dermatan Sulfate Revealed by Their Deficient Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Shuji Mizumoto ◽  
Shuhei Yamada
Keyword(s):  
Chondroitin Sulfate ◽  
Dermatan Sulfate ◽  
Biological Activities ◽  
Skeletal Development ◽  
Genetic Disorders ◽  
Collagen Fibrils ◽  
Comprehensive Overview ◽  
Core Proteins ◽  
Deficient Mice

Chondroitin sulfate (CS), dermatan sulfate (DS) and heparan sulfate (HS) are covalently attached to specific core proteins to form proteoglycans in their biosynthetic pathways. They are constructed through the stepwise addition of respective monosaccharides by various glycosyltransferases and maturated by epimerases as well as sulfotransferases. Structural diversities of CS/DS and HS are essential for their various biological activities including cell signaling, cell proliferation, tissue morphogenesis, and interactions with a variety of growth factors as well as cytokines. Studies using mice deficient in enzymes responsible for the biosynthesis of the CS/DS and HS chains of proteoglycans have demonstrated their essential functions. Chondroitin synthase 1-deficient mice are viable, but exhibit chondrodysplasia, progression of the bifurcation of digits, delayed endochondral ossification, and reduced bone density. DS-epimerase 1-deficient mice show thicker collagen fibrils in the dermis and hypodermis, and spina bifida. These observations suggest that CS/DS are essential for skeletal development as well as the assembly of collagen fibrils in the skin, and that their respective knockout mice can be utilized as models for human genetic disorders with mutations in chondroitin synthase 1 and DS-epimerase 1. This review provides a comprehensive overview of mice deficient in CS/DS biosyntheses.

scholarly journals Glycosaminoglycans in human neutrophils and leukemic myeloblasts: ultrastructural, cytochemical, immunologic, and biochemical characterization

Blood ◽  
1983 ◽  
Vol 61 (2) ◽  
pp. 257-266 ◽  
Author(s):  
RT Parmley ◽  
RE Hurst ◽  
M Takagi ◽  
SS Spicer ◽  
RL Austin
Keyword(s):  
Heparan Sulfate ◽  
Chondroitin Sulfate ◽  
Biochemical Characterization ◽  
Dermatan Sulfate ◽  
Myeloid Cells ◽  
Subcellular Location ◽  
Human Neutrophils ◽  
Normal Cells ◽  
Primary Granules ◽  
Primary Granule

Chondroitin sulfate is known to be present in normal and leukemic myeloid cells; however, its definitive subcellular location and association with other glycosaminoglycans (GAGs) has not been demonstrated. We have studied the type and distribution of GAGs in neutrophil granule subpopulations of normal and leukemic myeloid cells using ultrastructural, cytochemical, immunologic, and biochemical methods. At the ultrastructural level, high-iron diamine- thiocarbohydrazide-silver proteinate (HID-TCH-SP) stained sulfated glycoconjugates selectively in immature primary granules of normal promyelocytes and Auer rods and immature granules of leukemic myeloblasts. Staining was weak or absent in mature primary granules, whereas tertiary granules stained moderately. Primary granule staining with HID-TCH-SP was greatly diminished by prior treatment of the specimens with chondroitinase ABC and/or nitrous acid, indicating the presence of chondroitin sulfate and N-sulfated glycosaminoglycan. Immunostaining of myeloid cells with a rabbit antichondroitin 4-sulfate and ferritin-conjugated goat anti-rabbit IgG sequence resulted in staining of most primary granules. Biochemical analysis of GAGs from leukemic myeloblasts containing primary granules and Auer rods, but lacking secondary and tertiary granules, revealed 8 x 10(-17) mole of uronic acid/cell and electrophoretic and sulfaminohexose analysis showed 60%-70% chondroitin sulfate AC of heterogeneous molecular weight, 20%-30% of a GAG that most closely resembled heparan sulfate, and 10% dermatan sulfate. The lack of significant HID-TCH-SP staining of sulfate iin sites other than Auer rods and primary granules in leukemic myeloblasts indicates that these granules contain the chondroitin, dermatan, and heparan sulfate isolated from the same specimen. Similar GAGs are present in primary granules of normal cells as evidenced by their cytochemical and immunostaining properties. Thus, these studies demonstrate a heterogeneous population of GAGs not previously identified and localize these substances to the primary granule of leukemic and normal cells.

scholarly journals Thrombin adhesive properties: induction by plasmin and heparan sulfate.

1993 ◽  
Vol 123 (5) ◽  
pp. 1279-1287 ◽  
Author(s):  
R Bar-Shavit ◽  
Y Eskohjido ◽  
J W Fenton ◽  
J D Esko ◽  
I Vlodavsky
Keyword(s):  
Cell Surface ◽  
Heparan Sulfate ◽  
Chondroitin Sulfate ◽  
Dermatan Sulfate ◽  
Basement Membranes ◽  
Dependent Manner ◽  
Heparin Binding ◽  
Adhesive Properties ◽  
Adhesive Protein ◽  
Adhesive Molecule

We have previously demonstrated that chemically modified thrombin preparations induce endothelial cell (EC) adhesion, spreading and cytoskeletal reorganization via an Arg-Gly-Asp (RGD) sequence and the alpha v beta 3 integrin. Native thrombin, however, did not exhibit adhesive properties, consistent with crystal structure analysis, showing that Gly-Asp residues of the RGD epitope are buried within the molecule. We have now identified a possible physiological mean of converting thrombin to an adhesive protein. Plasmin, the major end product of the fibrinolytic system, converted thrombin to an adhesive protein for EC in a time and dose-dependent manner. EC adhesion and spreading was also induced by a low molecular weight (approximately 3,000 D) cleavage fragment generated upon incubation of thrombin with plasmin. Cell adhesion mediated by this fragment was completely inhibited by the synthetic peptide GRGDSP. Conversion of thrombin to an adhesive molecule was significantly enhanced in the presence of heparin or heparan sulfate, while other glycosaminoglycans (GAGs) (e.g., dermatan sulfate, keratan sulfate, chondroitin sulfate) had no effect. The role of cell surface heparan sulfate in thrombin conversion to EC adhesive protein was investigated using CHO cell mutants defective in various aspects of GAG synthesis. Incubation of both thrombin and a suboptimal amount of plasmin on the surface of formaldehyde fixed wild-type CHO-KI cells resulted in an efficient conversion of thrombin to an adhesive molecule, as indicated by subsequent induction of EC attachment. In contrast, there was no effect to incubation of thrombin and plasmin with fixed CHO mutant cells lacking both heparan sulfate and chondroitin sulfate, or with cells expressing no heparan sulfate and a three-fold increase in chondroitin sulfate. A similar gain of adhesive properties was obtained upon incubation of thrombin and plasmin in contact with native, but not heparinase-treated extracellular matrix (ECM) produced by cultured ECs. It appears that cell surface and ECM-associated heparan sulfate modulate thrombin adhesive properties through its heparin binding site in a manner that enables suboptimal amounts of plasmin to expose the RGD domain. Our results demonstrate, for the first time, a significant modulation of thrombin molecule by heparin, resulting in its conversion to a potent adhesive protein for ECs. This conversion is most effective in contact with cell surfaces, basement membranes and ECM.

Sulfated polysaccharides inhibit leukocyte rolling in rabbit mesentery venules

1991 ◽  
Vol 260 (5) ◽  
pp. H1667-H1673 ◽  
Author(s):  
K. Ley ◽  
M. Cerrito ◽  
K. E. Arfors
Keyword(s):  
Heparan Sulfate ◽  
Dextran Sulfate ◽  
Dermatan Sulfate ◽  
Leukocyte Adhesion ◽  
Keratan Sulfate ◽  
Mean Value ◽  
Sulfated Polysaccharides ◽  
Leukocyte Rolling ◽  
Chondroitin Sulfates ◽  
Wide Range

Before firm adhesion, leukocytes roll slowly along the walls of small venules at velocities ranging from 0.7 to 36% of mean blood flow velocity. To investigate the nature of the adhesive process underlying leukocyte rolling, synthetic (dextran sulfate) and naturally occurring sulfated polysaccharides (heparin, chondroitin sulfates, keratan sulfate, and heparan sulfate) were infused via glass micropipettes into the lumen of small venules (20–60 microns diam) of the rabbit mesentery. Leukocyte rolling was observed and quantified using both transmitted light and incident fluorescence intravital microscopy. Rolling leukocytes accounted for 27–80% of total leukocyte flux, exhibiting a wide range of individual velocities (0.01–0.84 mm/s) with a mean value of 4% of centerline velocity. Dextran sulfate (Mr 500,000) inhibited leukocyte rolling very effectively [half-effective concentration (ED50) approximately 10 micrograms/ml] and was able to almost completely abolish rolling at 500 micrograms/ml. Heparin (ED50 approximately 50 micrograms/ml), chondroitin 6-sulfate C (ED50 approximately 500 micrograms/ml), and heparan sulfate (ED50 approximately 5 mg/ml) also reduced leukocyte rolling. At 5 mg/ml, chondroitin 4-sulfate B (dermatan sulfate) was marginally effective, but chondroitin 4-sulfate A and keratan sulfate were ineffective. The present data suggest that an adhesion receptor-ligand system distinct from the leukocyte integrins may be underlying transient leukocyte adhesion (rolling). Endothelial glycoproteins or proteoglycans containing sulfated side chains may be involved in mediating this adhesive process.

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