Pathobiochemical Significance of Granulocyte Elastase Complexed with Proteinase Inhibitors: Effect on Glycosaminoglycan Metabolism in Cultured Synovial ...
Sulfated glycosaminoglycans were isolated from 23 species of 13 phyla of invertebrates and characterized by their electrophoretic migration in three different buffer systems coupled with enzymatic degradation using bacterial heparinase, heparitinases and chondroitinase AC. Heparan sulfate is a ubiquitous compound present in all species analyzed whereas chondroitin sulfate was present in 20 species and heparin-like compounds in 12 species of the invertebrates. the heparin-like compounds were purified from the echinoderm Mellita quinquisperforata (sand dollar) and the crustacean Ucides cordatus (crab) with anticoagulant activities of 60 and 52 IU/mg, respectively. Degradation of these heparins with heparinase produced significant amounts of the trisulfated disaccharide typical of mammalian heparins. This was confirmed by C-13-NMR spectroscopy of the crab heparin. An updated phylogenetic tree of the distribution of sulfated glycosaminoglycans in the animal kingdom is also presented. (C) 2000 ...
The human body actually produces its own glycosaminoglycans (GAGs). They work in part to regenerate and hydrate the dermal layer from the inside. Hydrolized glycosaminoglycans are slightly altered to enhance their water retentive ability. This sounds complicated, and the science involved probably is pretty complicated. The takeaway is that products containing hydrolized glycosaminoglycans are like super moisturizers that can penetrate where simple surface moisturizers cant go. Once absorbed into the skin, they also help repair and revitalize skin tissue, making it look softer, smoother, younger and healthier. Glycosaminoglycans are considered safe and effective, and youll find them in skin care as well as some hair care products.. Youre probably beginning to notice the important role proteins (and their constituent amino acids) play in the health of your skin. In addition to good hygiene and a consistent skin cleansing regimen, eating a diet high in protein can help your body make many of the ...
Methods and Results-chP3R99 mAb recognized sulfated glycosaminoglycans, mainly chondroitin sulfate (CS), by ELISA. This mAb blocked ≈70% of low-density lipoprotein (LDL)-CS association and ≈80% of LDL oxidation in vitro, and when intravenously injected to Sprague-Dawley rats (n=6, 1 mg/animal), it inhibited LDL (4 mg/kg intraperitoneally, 1 hour later) retention and oxidation in the artery wall. Moreover, subcutaneous immunization of New Zealand White rabbits (n=19) with chP3R99 mAb (100 μg, 3 doses at weekly intervals) prevented Lipofundin-induced atherosclerosis (2 mL/kg, 8 days) with a 22-fold reduction in the intima-media ratio (P,0.01). Histopathologic and ultrastructural studies showed no intimal alterations or slight thickening, with preserved junctions between endothelial cells and scarce collagen fibers and glycosaminoglycans. In addition, immunization with chP3R99 mAb suppressed macrophage infiltration in aorta and preserved redox status. The atheroprotective effect was associated ...
OBJECTIVES. Glycosaminoglycans (GAGs) are mucopolysaccharides (heparan, dermatan and chondroitin sulphates and hyaluronic acid), which can be found in different tissues of the body. In urinary tract, GAGs allow the formation of a layer of water/urine in the surface of the mucosa, protecting and also facilitating the elimination of bacteria during micturition. In women and cats, alteration of GAGs layer as well as reduction of urinary excretion of GAGs is mentioned in interstitial cystitis (IC). In dogs, low concentrations of urinary GAGs seem to be associated with recurrence of urinary infections and urolithiasis. Disorders of GAGs degradation and presence of large amount in urine can be observed in mucopolysaccharidosis. Most of GAGs laboratorial colorimetric methods reported develop in acid pH solution with DMB (colorant), but in this condition, DMB can also react with other urinary proteins. Jong (1992) mentioned a modified method, in which DMB reacts only with GAGs, forming a steady complex, ...
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HSGAG and CSGAG modified proteoglycans first begin with a consensus Ser-Gly/Ala-X-Gly motif in the core protein. Construction of a tetrasaccharide linker that consists of -GlcAβ1-3Galβ1-3Galβ1-4Xylβ1-O-(Ser)-, where xylosyltransferase, β4-galactosyl transferase (GalTI),β3-galactosyl transferase (GalT-II), and β3-GlcA transferase (GlcAT-I) transfer the four monosaccharides, begins synthesis of the GAG modified protein. The first modification of the tetrasaccharide linker determines whether the HSGAGs or CSGAGs will be added. Addition of a GlcNAc promotes the addition of HSGAGs while addition of GalNAc to the tetrasaccharide linker promotes CSGAG development.[5] GlcNAcT-I transfers GlcNAc to the tetrasaccahride linker, which is distinct from glycosyltransferase GlcNAcT-II, the enzyme that is utilized to build HSGAGs. EXTL2 and EXTL3, two genes in the EXT tumor suppressor family, have been shown to have GlcNAcT-I activity. Conversely, GalNAc is transferred to the linker by the enzyme GalNAcT ...
Quantitative biosynthetic studies with cultures highly enriched for glial fibrillary acidic protein (GFAP+) cells of neonatal mammalian brain demonstrated production of four proteoglycans: hyaluronate (HA), heparan sulphate (HS), chondroitin sulphate (CS), and dermatan sulphate (DS). The glycosaminoglycans were present in cell conditioned medium and in the cellular compartment. There were qualitative differences in the subcellular disposition of the various proteoglycans. The ratio of HS to CS/DS in cell extracts was 1:1, while in medium this ratio was 1:6. All of the glycosaminoglycans were associated with core proteins that were integral to the cell membrane and associated with the cell surface by non-covalent interactions involving glycosaminoglycans. Less than 20% of the HS was non-covalently associated with the astrocyte cell surface reflecting in part the proportionately smaller amounts of this proteoglycan released to astrocyte conditioned medium. HS released to medium was undersulphated relative
Proteoglycans (PGs) are composed of highly sulfated glycosaminoglycans chains (GAGs) attached to specific core proteins. They are present in extracellular matrices, on the cell surface and in storage granules of hematopoietic cells. Heparan sulfate (HS) and chondroitin/dermatan sulfate (CS/DS) GAGs play indispensable roles in a wide range of biological processes, where they can serve as protein carriers, be involved in growth factor or morphogen gradient formation and act as co-receptors in signaling processes. Protein binding abilities of GAGs are believed to be predominantly dependent on the arrangement of the sugar modifications, sulfation and epimerization, into specific oligosaccharide sequences. Although the process of HS and CS/DS assembly and modification is not fully understood, a set of GAG biosynthetic enzymes have been fairly well studied and several mutations in genes encoding for this Golgi machinery have been linked to human genetic disorders.. This thesis focuses on the zebrafish ...
What are Glucosamine Chondroitin and msm?. Articular cartilage is a connective tissue composed of specialized cells (chondrocytes) embedded in a matrix of protein fibers (mostly collagen) and clusters of complex proteoglycan molecules that consist of a protein core with numerous side chains. These side chains, chiefly chondroitin sulfate and keratin sulfate, are long polysaccharide molecules called glycosaminoglycans. Chondroitin sulfate (CS) and the other glycosaminoglycans strongly attract water due to the negative charges of their sulfate groups. These negative charges also repel each other, creating spaces between glycosaminoglycan side chains where water can enter. This combination of solid and liquid gives cartilage a compressible quality that allows it to function as a shock absorber for joints.1 Glucosamine is a fundamental building block for proteoglycans and glycosaminoglycans. Glucosamine sulfate (GS) helps to maintain joint health through its ability to both act as a component of and ...
What are Glucosamine Chondroitin and msm?. Articular cartilage is a connective tissue composed of specialized cells (chondrocytes) embedded in a matrix of protein fibers (mostly collagen) and clusters of complex proteoglycan molecules that consist of a protein core with numerous side chains. These side chains, chiefly chondroitin sulfate and keratin sulfate, are long polysaccharide molecules called glycosaminoglycans. Chondroitin sulfate (CS) and the other glycosaminoglycans strongly attract water due to the negative charges of their sulfate groups. These negative charges also repel each other, creating spaces between glycosaminoglycan side chains where water can enter. This combination of solid and liquid gives cartilage a compressible quality that allows it to function as a shock absorber for joints.1 Glucosamine is a fundamental building block for proteoglycans and glycosaminoglycans. Glucosamine sulfate (GS) helps to maintain joint health through its ability to both act as a component of and ...
Arterial glycosaminoglycans are considered to be important in atherogenesis due to their ability to trap lipid inside the vessel wall and to influence cellular migration and proliferation. Atherosclerotic lesions have displayed an altered glycosaminoglycan content and distribution. Diabetes is a rec …
Since the work of Watson & Pearce (1949) it has been known that subnormal thyroid activity affects the glycosaminoglycans (GAG) of skin. The changes reported were an increase in the hyaluronic acid and a decrease in the dermatan sulphate content of the skin (Schiller, Slover & Dorfman, 1962; Kofoed & Bozzini, 1967). These results seem to be independent of thyrotrophin because the same changes are noted after hypophysectomy as in hypothyroidism (Schiller et al. 1962). Since hypophysectomy has a different effect on skin and tracheal cartilage GAG (Kofoed & Bozzini, 1969), experiments were done to study the distribution of these compounds in cartilage of thyroidectomized rats and to compare this with the distribution in skin.. Female Wistar rats, weighing approx. 200 g., were used throughout these experiments. Thyroid destruction was accomplished by administration of 700 μc of 131I. Six months after radioactive iodine administration, rats were divided into three ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Heparan sulfate proteoglycans (HSPGs) have been extensively studied for their role in extracellular signaling. HSPGs interact with and regulate growth factors, chemokines, and cytokines. Signaling pathways for apoptosis, cellular development, and adhesion are regulated by proteoglycans. Genetic defects in heparan synthesis and modifying enzymes may affect growth factor signaling and produce morphological defects.8 Drosophila mutants and gene knockout mouse models have been used to eliminate critical heparan synthesis and modification enzymes, and subsequently identify the developmental processes disrupted. Experiments that use Drosophila containing mutations of the protein core of proteoglycans have been performed and have shown that the protein core also affects development. It has been theorized that both the HS and the protein core have roles in the mediation of growth factor binding and cell signaling.6. HS and HSPGs participate in fibroblast growth factor-2 (FGF-2) activation in response to ...
This study demonstrated that bovine sperm exposure to GAGs positively affected sperm fertilizing ability, in vitro embryo developmental potential, and embryonic gene expression. This is the first report to determine concurrently the effects of four different GAGs (HP, HA, CD, and DS). HP was the most potent GAG for enhancing sperm motility and inducing the acrosome reaction. HP exposed sperm exhibited improved 2 PN formation, cleavage rate, blastocyst formation rate, and embryo cell numbers relative to the control (p,0.05). Additionally, in embryos developing from fertilization with HP-treated sperm significant changes in gene expression were detected in genes involved in pluripotency (Oct4, upregulated), apoptosis (Bax inhibitor, upregulated; Caspase 3, downregulated), and cell growth (Glut5, upregulated), relative to control embryo gene expression (p,0.05). Sperm exposure to HA resulted in intermediate levels of changes, and, similar to HP, HA treatment of sperm resulted in significantly ...
Proteoglycans (PGs) are glycosylated proteins of biological importance at cell surfaces, in the extracellular matrix, and in the circulation. PGs are produced and modified by glycosaminoglycan (GAG) chains in the secretory pathway of animal cells. The most common GAG attachment site is a serine residue followed by a glycine (-ser-gly-), from which a linker tetrasaccharide extends and may continue as a heparan sulfate, a heparin, a chondroitin sulfate, or a dermatan sulfate GAG chain. Which type of GAG chain becomes attached to the linker tetrasaccharide is influenced by the structure of the protein core, modifications occurring to the linker tetrasaccharide itself, and the biochemical environment of the Golgi apparatus, where GAG polymerization and modification by sulfation and epimerization take place. The same cell type may produce different GAG chains that vary, depending on the extent of epimerization and sulfation. However, it is not known to what extent these differences are caused by
The tetra-branched peptide NT4 is a potential cancer theranostic, which very selectively binds to human cancer tissues in different malignancies and can efficiently and selectively deliver drugs or liposomes for cancer cell imaging or therapy, in vitro and in vivo. By using NT4 conjugated to methotrexate or 5FdU we obtained significant reduction of tumor growth in xenografted nude mice. Very recently we reported that conjugation of paclitaxel to NT4 leads to increased therapeutic activity of the drug in an orthotopic model of breast cancer in mice and produces tumor regression which is not achieved with unconjugated paclitaxel in identical experimental conditions. We demonstrated that NT4 specifically binds to sulfated glycosaminoglycans and LRP receptors on cancer cells and tissues.. Considering the role of sulfated glycosaminoglycans in cancer cell interaction with the extracellular matrix, we have analyzed the effect of NT4 in cancer cell adhesion and migration on different supports. NT4 ...
Glycosaminoglycan chains that project from proteoglycans of the arterial wall are responsible for the formation of complexes with plasma LDL.1 2 3 4 5 6 7 8 9 10 11 This is a step in the normal exchange of components between the circulating plasma and the arterial wall. However, during atherosclerosis, this process contributes to continuous focal deposition of cholesterol-rich lipoproteins, mainly LDL, in lesions.12 13 14 In turn, glycosaminoglycan-LDL complexes are more easily internalized by macrophages than LDL alone,15 thereby enhancing the formation of foam cells. Also, glycosaminoglycans induce structural alterations in LDL molecules that may potentiate their atherogenic effects.9 Therefore, the nature of the glycosaminoglycan-LDL interaction has been extensively studied. It is known that certain glycosaminoglycan species, including particular populations of a given species, have greater affinity for LDL.6 11 16 The occurrence of atherosclerotic lesions is associated with a number of risk ...
Cavalcanti, Alexandre B.; Berwanger, Otavio; Suzumura, Erica A.; Amato, Marcelo B. P.; Tallo, Fernando S.; Rezende, Ederlon A. C.; Telles, Jose M. M.; Romano, Edson; Guimaraes, Helio P.; Regenga, Marisa M.; Takahashi, Luzia N.; Teixeira, Cassiano; Oliveira, Roselaine P.; Carvalho, Vitor O.; Diaz-Quijano, Fredi A.; Carvalho, Carlos R. R.; Kodama, Alessandra A.; Ribeiro, Gisele F. M.; Abreu, Matheus O.; Oliveira, Ivonaldo M.; Guyatt, Gordon; Ferguson, Niall; Walter, Stephen; Vasconcelos, Marcia O. M.; Segundo, Valerio J.; Ferraz, Iris L.; Silva, Rosicley S.; Oliveira Filho, Wilson de; Silva, Nelson B.; Heirel, Debora C. B.; Takatani, Rodrigo R.; Sousa Neto, Jefferson A.; Neto, Jeronimo C. B.; Almeida, Samara D.; Chamy, Gauco; Goncalves Neto, Graciliano J. L.; Dias, Alysson P.; Silva, Rozangela R.; Tavares, Roberta C.; Souza, Marcia L. V. D.; Decio, Janaina C.; Lima, Cyntia M. L. S.; Ferreira Neto, Fleury; Oliveira, Katia R.; Dias, Polyana P. L. C.; Brandao, Andre L. S. B.; Ramos, Joroastro E.; ...
Chemokine cooperativity has previously been suggested to be caused by convergence of intracellular signaling pathways downstream of receptor activation (5-7, 11, 12). Our data indicate that chemokine cooperativity is not strictly dependent on the receptor of the cooperative chemokine. For example, mtCXCL12 and mtCXCL11 fully activate their respective G protein-coupled receptors (Supplemental Fig. 4) but do not cooperate with CCL21 (Fig. 4). Furthermore, RT-PCR analyses and cAMP measurements indicated that CHO-CCX-CKR cells do not express CXCR5 or CXCR4, the cognate Gαi-coupled receptors for CXCL13 and CXCL12, respectively (data not shown). Our data concur with previous evidence suggesting that activation of the receptor for the cooperative chemokine is not necessary for cooperativity (8, 9).. Alternatively, chemokine cooperativity has been suggested to originate from chemokine heterodimerization (9, 10). Our observation that both monomeric and dimeric CXCL12 species can induce chemokine ...
อ่านรีวิว Lasis Abalone Collagen Glycosaminoglycans จากผู้ใช้จริงทั่วประเทศ | V A N I L L A เว็บรีวิวเครื่องสำอางใหญ่ที่สุดในประเทศไทยจากผู้ใช้จริง มีทั้งหมด 331,832 รีวิว, 1,232 แบรนด์ และสินค้า 60,002 รายการ
The endothelium plays a crucial role in regulating vascular tone, inflammatory responses, thrombosis, and atherosclerosis. Part of these activities is regulated by the presence of glycosaminoglycans...
How GAGs in TWO STEP Work: When your pig consumes the patented blend of cartilage contained in TWO STEP the GAGs are absorbed from your pigs stomach into the body. The GAGs are probably broken down into proteoglycans first. The six different basic GAGs are similar in structure and composed of the same proteoglycans, so the various GAGs are somewhat interchangeable. After leaving the stomach, the GAGs reappear in the cartilage of the joints after having been carried by the blood system to the site near the cartilage and then migrating across cell membranes into the cartilage. There is no blood system in the cartilage which is why GAGS are somewhat slow acting. To help you better understand this, please find a diagram below of a synovial joint.. ...
adhesamine: synthetic diaryldispirotripiperazine that targets selective cell-surface glycosaminoglycans,especially heparan sulfate, for increasing cell adhesion and growth; a useful reagent for culturing neuronal cells
Development and use of sulodexide in vascular diseases: implications for treatment Sergio Coccheri,1 Ferdinando Mannello2 1Cardiovascular Medicine, University of Bologna, Bologna, 2Department of Biomolecular Sciences (Section Clinical Biochemistry and Cell Biology), University 'Carlo Bo', Urbino, Italy Abstract: Sulodexide (SDX), a sulfated polysaccharide complex extracted from porcine intestinal mucosa, is a blend of two glycosaminoglycan (GAG) entities, namely a fast-moving heparin (HP) fraction and a dermatan sulfate (DS; 20%) component. The compound is unique among HP-like substances in that it is biologically active by both the parenteral and oral routes. A main feature of the agent is to undergo extensive absorption by the vascular endothelium. For this reason, in preclinical studies, SDX administered parenterally displays an antithrombotic action similar to that of HPs but associated with fewer alterations of the blood clotting mechanisms and tests, thus being much less conducive to
... is an acidic mucopolysaccharide with the ability to prevent blood clotting. It is used in treating thrombosis. See also histamine ...
Miracle 10 is a Toronto based skincare line created by Dr. Frank Lista. Promoted as a "conservatively aggressive" skincare line that can stimulate collagen, elastin and glycosaminoglycan production in the skin. Miracle 10 is really just another doctor "created" skincare line that is becoming very popular with consumers. It is important to note that, regardless of the ad copy, these products are topical cosmetics and as such, will provide results similar to any well-formulated product. There is not one single ingredient used in Miracle 10 that cannot be found in countless product ranges ...
Miracle 10 is a Toronto based skincare line created by Dr. Frank Lista. Promoted as a "conservatively aggressive" skincare line that can stimulate collagen, elastin and glycosaminoglycan production in the skin. Miracle 10 is really just another doctor "created" skincare line that is becoming very popular with consumers. It is important to note that, regardless of the ad copy, these products are topical cosmetics and as such, will provide results similar to any well-formulated product. There is not one single ingredient used in Miracle 10 that cannot be found in countless product ranges ...
Blockage from the metastasis procedure remains a substantial clinical problem requiring innovative therapeutic techniques. N6L inhibited Matrigel invasion of MDA-MB-435 cells inside a revised Boyden chamber model. This is associated with a rise in TIMP-3 within the cell tradition medium with out a modification in TIMP-3 mRNA manifestation suggesting its launch from cell surface area and/or extracellular matrix. This can be described by our proven N6L discussion with sulfated glycosaminoglycans and therefore the managed bioavailability of glycosaminoglycan-bound TIMP-3. The Rabbit Polyclonal to OR4A16. implication of TIMP-3 in N6L-induced inhibition of cell invasion was evidenced by siRNA silencing tests showing that the increased loss of TIMP-3 manifestation abrogated the result of N6L. The inhibition of tumor cell invasion by N6L proven in this research furthermore to its previously founded inhibitory influence on tumor development and angiogenesis shows that N6L represents a guaranteeing ...
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Interacting selectively and non-covalently with heparin, any member of a group of glycosaminoglycans found mainly as an intracellular component of mast cells and which consist predominantly of alternating alpha-(1-|4)-linked D-galactose and N-acetyl-D-glu…
H. Tavakoli Nia, Ortiz, C., and Grodzinsky, A., "Aggrecan: Approaches to Study Biophysical and Biomechanical Properties", in Glycosaminoglycans: Chemistry and Biology, vol. 1229, K. Balagurunathan, Nakato, H., and Desai, U. R. 2015, pp. 221 - 237. ...
Glucosamine is an important building block needed by the body to manufacture specialized molecules called glycosaminoglycans, found in cartilage.
Graham, G. J. , Handel, T. M. and Proudfoot, A. E.I. (2019) Leukocyte adhesion: reconceptualizing chemokine presentation by glycosaminoglycans. Trends in Immunology, 40(6), pp. 472-481 ...
But this distinction was not located in G. Proteoglycan Wnt signaling pathway ranges The amounts of HA and GAG are revealed in Fig. In the seventy two h tradition non U0126 dealt with with IL 1, ...
The effect of W. somnifera on glycosaminoglycan synthesis in the granulation tissue of carrageenin-induced air pouch granuloma was studied. W. somnifera was shown to exert significant inhibitory effect on incorporation of /sup 35/S into the granulation tissue. The uncoupling effect on oxidative phosphorylation (ADP/O ratio reduction) was also observed in the mitochondria of granulation tissue. Further, Mg/sup 2 +/ dependent ATPase activity was found to be influenced by W. somnifera. W. somnifera also reduced the succinate dehydrogenase enzyme activity in the mitochondria of granulation tissue. ...
TY - JOUR. T1 - The effect of dexamethasone on glycosaminoglycans of human trabecular meshwork in perfusion organ culture. AU - Johnson, D. H.. AU - Bradley, J. M B. AU - Acott, Ted. PY - 1990. Y1 - 1990. N2 - The effect of dexamethasone treatment on glycosaminoglycans (GAG) in the human trabecular meshwork was studied by placing 20 pairs of eyes in perfusion organ culture. One eye received 550 nM dexamethasone in addition to culture medium; the fellow eye received culture medium only. 3H-glucosamine and 35S-sulfate were added to the medium for the final 48 hr of culture. The meshwork was then dissected, and the GAGs were isolated and subjected to sequential enzymatic degradation. Active labeling of hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, and heparan sulfate was found in both control and steroid-treated eyes. Dexamethasone-treated eyes had an average 92% increase in the 3H-glucosamine incorporation rate in the undigestible GAG residue fraction after 14-21 days ...
Cartilage tissue specimens were obtained from the flexor surface of the navicular bone and distal radiocarpal bone articular surface (controls) from 8 horses 2 to 5 years old. Water, DNA, total collagen, total glycosaminoglycans, chondroitin sulphate, and keratan sulphate contents were determined. The results from each site were compared and the differences were analyzed by paired t-test (P < 0.05). Significant differences were determined between the water content of the navicular bone flexor surface cartilage (68.32± 3.46 % ) and the distal radiocarpal bone articular surface cartilage (60.60± 4.09%). The total DNA content, total glycosaminoglycan content, total chondroitin sulphate content, and total keratan sulphate for the flexor surface of the navicular bone was: 524.51± 92.89 ng, 0.1533± 0.0338 mg, 0.1018± 0.0197 mg 0.0800± 0.0176 mg, and 0.0092± 0.0037 mg per mg of dry weight cartilage, respectively. The total DNA content, total glycosaminoglycan content, total chondroitin sulphate ...
Xenopus laevis is an excellent animal for analyzing early vertebrate development. Various effects of glycosaminoglycans (GAGs) on growth factor-related cellular events during embryogenesis have been demonstrated in Xenopus. To elucidate the relationship between alterations in fine structure and changes in the specificity of growth factor-binding during Xenopus development, heparan sulfate (HS) and chondroitin/dermatan sulfate (CS/DS) chains were isolated at four different embryonic stages and their structure and growth factor-binding capacities were compared. The total amounts of both HS and CS/DS chains decreased from the pre-midblastula transition to the gastrula stage, but increased exponentially during the following developmental stages. The length of HS chains was not significantly affected by development, whereas that of CS/DS chains increased with development. The disaccharide composition of GAGs in embryos also changed during development. The degree of sulfation of the HS chains ...
Loss of glycosaminoglycan (GAG) chains of proteoglycans (PGs) is an early event of osteoarthritis (OA) resulting in cartilage degradation that has been previously demonstrated in both huma and experimental OA models. However, the mechanism of GAG loss and the role of xylosyltransferase-I (XT-I) that initiates GAG biosynthesis onto PG molecules in the pathogenic process of human OA are unknown. In this study, we have characterized XT-I expression and activity together with GAG synthesis in human OA cartilage obtained from different regions of the same joint, defined as normal, late-stage or adjacent to late-stage. The results showed that GAG synthesis and content increased in cartilage from areas flanking OA lesions compared to cartilage from macroscopically normal unaffected regions, while decreased in late-stage OA cartilage lesions. This increase in anabolic state was associated with a marked upregulation of XT-I expression and activity in cartilage next to lesion while a decrease in the
Background-Heart failure (HF) is a leading cause of mortality and morbidity, and the search for novel therapeutic approaches continues. In the monogenic disease mucopolysaccharidosis (MPS) VI, loss of function mutations in arylsulfatase B (ASB) leads to myocardial accumulation of chondroitin sulfate (CS) glycosaminoglycans (GAGs), manifesting as a myriad of cardiac symptoms. Here, we studied changes in myocardial CS in non-MPS failing hearts, and assessed its generic role in pathological cardiac remodeling. Methods-Healthy and diseased human and rat left ventricles were subjected to histological and immuno-staining methods to analyze for GAG distribution. GAGs were extracted and analyzed for quantitative and compositional changes using Alcian Blue assay and liquid chromatography mass spectrometry. Expression changes in 20 CS-related genes were studied in three primary human cardiac cell types and THP-1 derived macrophages under each of 9 in vitro stimulatory conditions. In two rat models of ...
Metachromasia (var. metachromasy) is a characteristic change in the color of staining carried out in biological tissues, exhibited by certain dyes when they bind to particular substances present in these tissues, called chromotropes. For example, toluidine blue becomes dark blue (with a colour range from blue-red dependent on glycosaminoglycan content) when bound to cartilage. Other widely used metachromatic stains are the haematological Giemsa and May-Grunwald stains that also contain thiazine dyes. The white cell nucleus stains purple, basophil granules intense magenta, whilst the cytoplasms (of mononuclear cells) stains blue. The absence of color change in staining is named orthochromasia. The underlying mechanism for metachromasia requires the presence of polyanions within the tissue. When these tissues are stained with a concentrated basic dye solution, such as toluidine blue, the bound dye molecules are close enough to form dimeric and polymeric aggregates. The light absorption spectra of ...
Heparan sulfate (HS) and heparin (Hep) are glycosaminoglycans with repeating disaccharide units that consist of alternating residues of alpha-D-glucosamine (GlcN) and uronic acid, the latter being either beta-D-glucuronic acid (GlcA) or alpha-L-iduronic acid (IdoA). In these sugar residues, sulfation modification may be performed at various positions. Structural studies show that Hep possesses a higher degree of sulfation than HS. The biosynthesis of HS/Hep occurs with the addition of the first GlcNAc residue by EXTL3 glycosyltransferase after completion of tetrasaccharide linkage region attached to serine residue of a core protein. The chain polymeraization is then catalyzed by EXT1 and EXT2 transferases. As the chain polymerizes, HS/Hep undergoes a series of modification reactions including N-deacetylation, N-sulfation, epimerization, and subsequently O-sulfation. As final products of biosynthesis, HS is present in the form of hepran sulfate proteoglycan (HSPG) whereas Hep exists as a sugar ...
Protein transduction domains (PTDs) are powerful nongenetic tools that allow intracellular delivery of conjugated cargoes to modify cell behavior. Their use in biomedicine has been hampered by inefficient delivery to nuclear and cytoplasmic targets. Here we overcame this deficiency by developing a series of novel fusion proteins that couple a membrane-docking peptide to heparan sulfate glycosaminoglycans (GAGs) with a PTD. We showed that this GET (GAG-binding enhanced transduction) system could deliver enzymes (Cre, neomycin phosphotransferase), transcription factors (NANOG, MYOD), antibodies, native proteins (cytochrome C), magnetic nanoparticles (MNPs), and nucleic acids [plasmid (p)DNA, modified (mod)RNA, and small inhibitory RNA] at efficiencies of up to two orders of magnitude higher than previously reported in cell types considered hard to transduce, such as mouse embryonic stem cells (mESCs), human ESCs (hESCs), and induced pluripotent stem cells (hiPSCs). This technology represents an ...
Description: The formation of a cross-link between peptide chains mediated by a chondroitin 4-sulfate glycosaminoglycan that originates from a typical O-glycosidic link to serine of one chain; the other chain is esterified, via the alpha-carbon of its C-terminal Asp, to C-6 of an internal N-acetylgalactosamine of the glycosaminoglycan chain.. ...
Controlled release systems for therapeutic molecules are vital to allow the sustained local delivery of their activities which direct cell behaviour and enable novel regenerative strategies. Direct programming of cells using exogenously delivered transcription factors can by-pass growth factor signalling but there is still a requirement to deliver such activity spatio-temporally. We previously developed a technology termed GAG-binding enhanced transduction (GET) to efficiently deliver a variety of cargoes intracellularly, using GAG-binding domains which promote cell targeting, and cell penetrating peptides (CPPs) which allow cell entry. Herein we demonstrate that GET system can be used in controlled release systems to mediate sustained intracellular transduction over one week. We assessed the stability and activity of GET peptides in poly(dl-lactic acid-co-glycolic acid) (PLGA) microparticles (MPs) prepared using a S/O/W double emulsion method. Efficient encapsulation (∼65%) and tailored ...
Methyl-Sulfonyl- Methane Suitable for Vegetarians USAGE: Take 1 scoop once or twice a day, or as directed by your qualified health consultant. Jarrow Formulas MSMSulfur is an organic source of bioavailable sulfur, an antioxidant mineral found in major structural molecules of the body such as cartilage. The sulfur from MSM is used to produce glycosaminoglycans (or mucopolysaccharides) such as chondroitin sulfate, dermatan sulfate and hyaluronic acid. These sulfur containing glycosaminoglycans are found in high concentrations in connective tissue, including joint cartilage, skin and collagen. Do NOT take if pregnant, lactating, trying to conceive, or have a medical condition. For best results, use with Jarrow Formulas BioSil, the concentrated, Biologically Active Silicon for stronger, healthier bones, joints and skin. Keep out of the reach of children. SUPPLEMENT FACTS Serving Size 1 Capsule Amount % DV -------------------------------------------------------------------------------
Proteoglycans Proteoglycans are molecules composed of a polypeptide and one or several sulfated glycosaminoglycans attached by chemical bindings. They are found in every animal tissue. Almost every cell may synthesize proteoglycans, and then they are released, incorporated in the plasma membrane or stored in internals vesicles. They are essential molecules of the pericellular space. Proteoglycans are assembled inside the cell. The polypeptide is synthesized in the endoplasmic reticulum, where some monosaccharides are also added. However, the elongation of the glycosaminoglycan chains, as well as the addition of sulfate groups, occurs in the trans domain of the Golgi complex. Most of the proteoglycans are exocytosed to the extracellular space, but some of them will be part of the plasma membrane, where they are inserted among the fatty acid chains of lipids thanks to a sequence of hydrophobic amino acids of the polypeptide Different proteoglycans show different amino acid sequence and polypeptide ...