Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.6.4 (chondroitinase)
2,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A chondroitinase that acts upon chondroitin sulfate C and hyaluronic acid was isolated from Flavobacterium heparinum. This enzyme was seperated from constitutional chondroitinase AC and an induced chondroitinase B also present in extracts of F. heparinum previously grown in the presence of chondroitin sulfates A, B or C. The enzyme acts upon chondroitin sulfate C producing tetrasaccharide plus an unsaturated 6-sulfated disaccharide (delta Di-6S), and upon hyaluronic acid producing unsaturated nonsulfated disaccharide (delta Di-OS). Chondroitin sulfate A is also degraded producing oligosaccharides and delta Di-6S but not delta Di-4S. The chondroitinase C is also distinguished from the chondroitinases B and AC by several properties, such as effect of ions, temperature for optimal activity, and susceptibility to increasing salt concentrations. The substrate specificity of the chondroitinase C is different from that of any other chondroitinase or hyaluronidase described so far.
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PMID:Chondroitinase C from Flavobacterium heparinum. 0 3

Heparin-like glycosaminoglycans (GAG) were isolated from commerical Vessel and their biologic properties studied. Vessel was found to be a mixture of chondroitin sulfates, dermatan sulfate and heparin-like GAG. Chondroitin sulfates and dermatan sulfate in Vessel were hydrolyzed by chondroitinase ABC and the residual Vessel was fractionated on a Dowex-1 Cl- column eluting with a stepwise-increasing concentration of NaCl (1.2--4.0 M). The major fractions eluted at 1.6 M and 1.8 M NaCl were tentatively identified by chemical analysis as heparin-like GAG with somewhat lower sulfate content than standard heparin. Both fractions had lipoprotein lipase-releasing activity and anticoagulant activity similar to heparin, but 1.6 M NaCl fraction had a third of the anticoagulant activity of standard heparin. The 1.8 M NaCl fraction complexed with serum lipoproteins similarly to heparin. In preliminary studies cholesterol-fed rabbits treated with Vessel exhibited somewhat less atherosclerosis than controls.
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PMID:Studies of glycosaminoglycan composition and biologic activity of Vessel, a hypolipidemic agent. 72 39

Glycosaminoglycans (GAGs) including chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin, and keratan sulfate types I (corneal) and II (cartilage) added to buffer, plasma and urine were enzymatically depolymerized. Enzymes, including chondroitin ABC lyase (chondroitinase ABC), heparin lyase (heparinase), heparan sulfate lyase (heparitinase), endo-beta-galactosidase and keratanase were used to depolymerize each GAG. Depolymerized GAGs and GAG mixtures were fractionated using gradient polyacrylamide gel electrophoresis. Staining with alcian blue dye resulted in a distinctive and well resolved banding pattern for each GAG. When these same gels were silver stained, an increase in detection sensitivity of 1000-fold was obtained. Picogram quantities of an oligosaccharide standard in buffer could be detected with silver staining while nanogram quantities could be detected in urine or plasma. The banding pattern observed for each depolymerized GAG was well resolved from contaminants found in these biological fluids and from intact GAGs. Endogenous GAGs present in samples of human urine and plasma were first concentrated and then enzymatically depolymerized. Chondroitin or dermatan sulfates, heparan sulfate and keratan sulfate were each detected in both concentrated plasma and urine samples.
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PMID:Electrophoresis and detection of nanogram quantities of exogenous and endogenous glycosaminoglycans in biological fluids. 171 41

Studies on cell behaviour in vitro have indicated that the chondroitin sulphate proteoglycan (CSPG) family of molecules can participate in the control of cell proliferation, differentiation and adhesion, but its morphogenetic functions had not been investigated in intact embryos. Chondroitin/chondroitin sulphates have been identified in rat embryos at low levels at the start of neurulation (day 9) and at much higher levels on day 10. In this study we have sought evidence for the morphogenetic functions of CSPGs in rat embryos during the period of neurulation and neural crest cell migration by a combination of two approaches: immunocytochemical localization of CSPG by means of an antibody, CS-56, to the chondroitin sulphate component of CSPG, and exposure of embryos to the enzyme chondroitinase ABC. Staining of the CS-56 epitope was poor at the beginning of cranial neurulation; bright staining was at first confined to the primary mesenchyme under the convex neural folds late on day 9. In day 10 embryos, all mesenchyme cells were stained, but at different levels of intensity, so that primary mesenchyme, neural crest and sclerotomal cells could be distinguished from each other. Basement membranes were also stained, particularly bright staining being present where two epithelial were basally apposed, e.g., neural/surface ectoderms, dorsal aorta/neural tube, prior to migration of a population of cells between them. Staining within the neural epithelium was first confined to the dorsolateral edge region, and associated with the onset of neural crest cell emigration; after neural tube closure, neuroepithelial staining was more general. Neural crest cells were stained during migration, but the reaction was absent in areas associated with migration end-points (trigeminal ganglion anlagen, frontonasal mesenchyme). Embryos exposed to chondroitinase ABC in culture showed no abnormalities until early day 10, when cranial neural crest cell emigration from the neural epithelium was inhibited and neural tube closure was retarded. Sclerotomal cells failed to take their normal pathway between the dorsal aorta and neural tube. Correlation of the results of these two methods suggests: (1) that by decreasing adhesiveness within the neural epithelium at specific stages, CSPG facilitates the emigration of neural crest cells and the migratory movement of neuroblasts, and may also provide increased flexibility during the generation of epithelial curvatures; (2) that by decreasing the adhesiveness of fibronectin-containing extracellular matrices, CSPG facilitates the migration of neural crest and sclerotomal cells. This second function is particularly important when migrating cells take pathways between previously apposed tissues.
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PMID:Immunohistochemical localisation of chondroitin sulphate proteoglycans and the effects of chondroitinase ABC in 9- to 11-day rat embryos. 256 69

Calf and mature cow articular cartilage was labeled in vitro with [35S]SO4 and [3H]glycine and kinetics of incorporation of both isotopes by cartilage fragments was determined by scintillation spectroscopy. The cartilage fragments were then extracted in sequence with 4M GuHCl (Guanidium chloride) and pepsin. The pepsin digest was adjusted to 1.3 M NaCl and pepsin-solubilized collagen salted out. The 4M GuHCl extract, collagen and pepsin-resistent residue were then freeze-dried. The 4M GuHCl extract was further fractionated by DEAE (Diethylaminoethyl) 52 ion exchange chromatography to obtain protein and PG (Proteoglycan) fractions. The protein fraction was also characterised by SDS-PAGE and PG fraction by Sepharose C1-2B chromatography under associative conditions in the presence and absence of an exogenous HA (Hyaluronic acid). The GAG (Glycosaminoglycan) side chains of the PG samples were analysed by Sephadex G-200 column chromatography and their composition determined by paper chromatography after chondroitinase ABC digestion. Linear incorporation of both isotopes was observed from 1 to 18 hours of incubation and roughly equal amounts of [35S]SO4 counts were found on per cell bases in both cartilages although less [3H]glycine was incorporated by cow chondrocytes. It was also found that calf chondrocytes synthesize much greater proportion of the collagen whereas the cow cells synthesize PGs of smaller hydrodynamic sizes, bearing shorter GAG side chains that are enriched in KS (Keratan sulfate) and Ch-6S (Chondroitin-6 sulfate isomer). A failure of cow 35S-PGs monomers to interact with an exogenous HA in the presence of other extracted components was also demonstrated. The relevance of these findings for the mechanism of cartilage damage in aging and osteoarthritis is discussed.
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PMID:Age-related changes in the synthesis of matrix macromolecules by bovine articular cartilage. 280 79

Immunohistochemical localization of chondroitin sulphate and dermatan sulphate proteoglycans (PGs) was observed in 70 tumour tissues, using monoclonal antibodies 9A-2 and 3B-3 raised against core molecules obtained from chondroitin sulphate PG by chondroitinase ABC-treatment. They recognize a stub of delta Di-4S and delta Di-6S binding to core protein via a linkage tetrasaccharide, respectively. The antibody 6B6 raised against dermatan sulphate PG obtained from an ovarian fibroma capsule in our laboratory was also used. The interstitial fibrous elements, so-called 'specific stroma' within the cancer cell nests contained chondroitin 4-sulphate PG as revealed with 9A-2, whereas the surrounding connective tissue and the preexisting fibrous connective tissue involved in the tumour growth consisted of dermatan sulphate PG with a considerable amount of chondroitin 4-sulphate PG. Chondroitin 6-sulphate PG as revealed with 3B-3 was located in the connective tissue proliferating from blood vessels and muscle tissue in association with the invasive growth of tumour cells. Chondroitin 6-sulphate PG was also observed in the basement membrane components of some tumours. In non-epithelial tumours (fibrogenic, chondrogenic, osteogenic and neurogenic tumours), chondroitin 4-sulphate was in fibrous portions. When collagenization and hyalinization progressed, dermatan sulphate PG was observed to increase in quantity.
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PMID:Immunohistochemical localization of chondroitin sulphate and dermatan sulphate proteoglycans in tumour tissues. 334 50

Chondroitin, chondroitin 6-sulphate, chondroitin 4-sulphate and dermatan sulphate proteoglycans were immunolocalized by monoclonal antibodies applied to human muscle sections digested with chondroitinase. In normal muscle the 4 proteoglycans presented a different extracellular localization: unsulphated chondroitin sulphate (chondroitin) was present in the endomysium and around capillaries, chondroitin 6-sulphate in the basal membrane zone, chondroitin 4-sulphate in the vessel adventitia, in the endomysium around capillaries and, to a lesser degree, in the perimysium, dermatan sulphate in the perimysium and, to a lesser extent, in the vessel adventitia and in the endomysium around capillaries. The enlarged endomysium of pathological muscle contained chondroitin and chondroitin 4-sulphate. Chondroitin 6-sulphate and dermatan sulphate did not seem present in the increased connective tissue. No peculiar pattern was observed in the various neuromuscular diseases studied. The specific extracellular distribution, the different biochemical composition and the different ability to bind to other extracellular components suggest a different biological role of these compounds. Chondroitin 6-sulphate is a component of a highly specialized extracellular structure, namely basal membrane. Chondroitin and chondroitin 4-sulphate participate in the composition of actively changing extracellular matrix such as the endomysium in pathological muscle. On the other hand, dermatan sulphate is a constituent of the perimysium that is a more static extracellular structure.
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PMID:Chondroitin, chondroitin 6-sulphate, chondroitin 4-sulphate and dermatan sulphate proteoglycans in normal and pathological human muscle. 369 31

Chondroitin 4-sulphate, chondroitin 6-sulphate, dermatan sulphate and keratan sulphate were N-deacetylated by treatment with hydrazine and then cleaved with HNO2 at pH 4.0, and the resulting products were reduced with NaB3H4. This reaction sequence cleaved the glycosaminoglycans at their N-acetyl-D-glucosamine or N-acetyl-D-galactosamine residues, which were converted into 3H-labelled 2,5-anhydro-D-mannitol (AManR) or 2,5-anhydro-D-talitol (ATalR) residues respectively. The end-labelled disaccharides, composed of D-glucuronic acid (GlcA), L-iduronic acid (IdoA) or D-galactose (Gal) and one of the anhydrohexitols, were identified as follows: both chondroitin 4-sulphate and chondroitin 6-sulphate gave GlcA----ATalR(4-SO4), GlcA----ATalR(6-SO4), IdoA----ATalR (4-SO4) and GlcA(2-SO4)----ATalR(6-SO4); dermatan sulphate gave IdoA----ATalR(4-SO4), GlcA----ATalR(4-SO4), GlcA----ATalR(6-SO4)----IdoA(2-SO4)ATalR(4-SO4) and IdoA----ATalR (4,6-diSO4); keratan sulphate gave Gal(6-SO4)----AManR(6-SO4), Gal----AManR(6-SO4), Gal(6-SO4)----AManR and Gal----AManR. Several additional disaccharides were generated by treatment of the uronic acid-containing disaccharides with hydrazine to epimerize their uronic acid residues at C-5. A number of these disaccharides were found to be substrates for lysosomal sulphatases and glycuronidases. Methods were developed for the separation of all of the disaccharide products by h.p.l.c. The rate of N-deacetylation of chondroitin 4-sulphate by hydrazinolysis was significantly lower than the rate of N-deacetylation of chondroitin 6-sulphate or chondroitin. Dermatan sulphate was N-deacetylated at an intermediate rate. The relative amounts of disaccharides obtained from chondroitin 4-sulphate, chondroitin 6-sulphate and dermatan sulphate under optimum hydrazinolysis/deamination conditions were comparable with the amounts of the corresponding products released from the polymers by chondroitinase treatment.
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PMID:The disaccharides formed by deaminative cleavage of N-deacetylated glycosaminoglycans. 374 82

Type IX collagen was isolated as a native protein from chicken embryo sternal cartilages and purified to homogeneity. Chondroitin and/or dermatan sulfate were bound covalently to one of the three polypeptide chains present in this protein containing collagenous and noncollagenous domains. Type IX collagen could be metabolically labeled with both radioactive sulfate and glycine. The protein containing either of these labels was sensitive to digestion by bacterial collagenase as well as chondroitinase ABC. Besides the glycosaminoglycans, type IX collagen contains asparagine-linked carbohydrate chains because the protein could be labeled with radioactive mannose and no glycosaminoglycans other than those mentioned above were present. The melting curve indicated that, in contrast to interstitial collagens, this molecule contains at least two disulfide-bonded collagenous domains with distinct thermal stabilities.
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PMID:Type IX collagen from sternal cartilage of chicken embryo contains covalently bound glycosaminoglycans. 385 2

Rat brain extracts contain two heat-stable, nondialyzable inhibitors of tubulinyl-tyrosine carboxypeptidase. One of the inhibitors was sensitive to ribonuclease and insensitive to trypsin and pronase, indicating that the inhibitor is RNA. This is supported by the observation that purified RNA from rat brain inhibited the enzyme activity to the same extent as similar amounts of the endogenous RNA. Similar results were obtained with calf liver RNA. The other inhibitor was purified by chromatography on a DEAE-Sephadex and identified as proteoglycan. The elimination of the protein moiety of the proteoglycan resulted in a small increase of its inhibitory activity. Glycosaminoglycan was released from the proteoglycan by beta elimination, indicating that the linkage between glycosaminoglycan and the protein moiety is through an O-glycosidic bond. The glycosaminoglycan contains uronic acid, hexosamine and sulfate in a molar ratio of 1:1.01:0.99, respectively. Treatment of the glycosaminoglycan with chondroitinase ABC completely abolished its inhibitory activity. Chondroitin sulfate A, chondroitin sulfate B, chondroitin sulfate C, and the brain glycosaminoglycan inhibited tubulinyl-tyrosine carboxypeptidase to the same extent when used in comparable amounts.
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PMID:Inhibition of tubulinyl-tyrosine carboxypeptidase by brain soluble RNA and proteoglycan. 616 Nov 29


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