Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The surface of rat arterial smooth muscle cells was characterized with respect to some of its chemical and functional properties. The effects of selective enzymic degradations (hyaluronidase, chondroitinases, heparitinase or neuraminidase) on [35S]sulphate-prelabelled cells and on binding sites for cationized ferritin (CF) were examined to assess the presence and relative importance of individual species of macromolecules on the cell surface. The results indicate that about half of the strongly anionic sites on the cell surface (binding CF at pH 2.0) could be ascribed to sulphate groups of glycosaminoglycans and about half to carboxyl groups of sialic acid residues in glycoproteins and/or glycolipids. Weaker anionic sites (binding CF at pH 7.0) largely originated from carboxyl groups of glycosaminoglycans. Chondroitin sulphate and heparan sulphate were the main glycosaminoglycans. The surface of cells from young animals showed a higher glycosaminoglycan and a lower sialic acid content than that of cells from adult animals. Continuous treatment of the cultures with neuraminidase stimulated serum-induced initiation of DNA synthesis, while treatment with hyaluronidase or heparitinase inhibited it. Addition of hyaluronic acid, heparin or heparan sulphate to the culture medium inhibited initiation of DNA synthesis as well as cell proliferation. The effect was more marked in cultures of cells from young animals than from adults, although the latter cells were found to grow at a higher rate and to higher densities. These results suggest a role for cell-surface and pericellular glycoconjugates in growth regulation. A possible mechanism of action is that these molecules, due to their anionic charge or by steric exclusion, interfere with the binding of platelet-derived growth factor, a highly cationic polypeptide, to its cell-surface receptor.
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PMID:Cell surface components and growth regulation in cultivated arterial smooth muscle cells. 642 Apr 21

Age-related changes in renal function have been attributed to alterations in the chemical composition of the kidney tissues. Hence, the glycosaminoglycan composition of the renal cortex and medulla at varying age intervals was investigated. Glycosaminoglycans were isolated from the tissues by means of digestion with collagenase and pronase and purified by ethanol precipitation. Subsequent separation of various polyanions was accomplished by ion exchange chromatography on a Dowex 1-X2 column, using sodium chloride buffers of increasing ionic strengths. The glycosaminoglycans in each fraction were identified and quantitated by digestion with specific enzymes, including hyaluronidase, chondroitinase AC and ABC. The enzyme resistant material was separated and further digested with nitrous acid to quantitate the proportion of heparon sulfate. The results indicate that the glycosaminoglycan content of the renal medulla was much higher than the cortex at all the age intervals studied, and age-induced reduction was mainly cortical. There was a significant reduction in the heparan sulfate content of the cortex in aging. Interestingly, the major glycosaminoglycan content of the medulla was hyaluronic acid, which showed a sharp increase during aging, whereas heparan sulfate declined. Chondroitin sulfate was not altered due to age in either tissue. The molecular weight of hyaluronic acid was determined by column chromatography. Results indicate that the size of hyaluronate in the cortex was small and did not vary with age. In the medulla of the younger age group, a considerable amount of large size hyaluronate was observed. As age increased, the size decreased. The results strongly suggest that alteration in the renal glycosaminoglycans may be partly responsible for the age related protinuria and ionic imbalance.
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PMID:Alterations of renal cortex and medullary glycosaminoglycans in aging dog kidney. 662 71

Chondroitin sulfate lyase (EC 4.2.2.4) was present constitutively at low levels (0.06 to 0.08 U/mg of protein) in cells of Bacteroides thetaiotaomicron which were growing on glucose or other monosaccharides. When these uninduced bacteria were incubated with chondroitin sulfate A (5 mg/ml), chondroitin sulfate lyase specific activity increased more than 10-fold within 90 min. Synthesis of ribonucleic acid and of protein was required for induction, and induction was sensitive to oxygen. The disaccharides which resulted from chondroitinase action did not act as inducers, nor did tetrasaccharides or hexasaccharides obtained by digestion of chondroitin sulfate with bovine testicular hyaluronidase. None of these substances was taken up by uninduced cells; they may not have been able to penetrate the outer membrane. The smallest oligomer capable of acting as an inducer was the outer membrane. The smallest oligomer capable of acting as an inducer was the octassacharide. Oligomers larger than the octassacharide induced chondroitin lyase activity nearly as well as intact chondroitin sulfate.
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PMID:Induction of chondroitin sulfate lyase activity in Bacteroides thetaiotaomicron. 678 77

We investigated the chondroitin sulfate in human periodontal samples (gingiva, periodontal ligament, cementum and alveolar bone) collected for orthodontic reasons. Glycosaminoglycans (GAGs) were extracted from the periodontium by enzyme digestion, and unsaturated disaccharide isomers of chondroitin sulfate were obtained by chondroitinase ACII and hyaluronidase digestion. The isomers were analyzed by high-performance liquid chromatography. Chondroitin sulfate was found in all four types of periodontal tissue; its unsaturated disaccharide isomers consisted in delta Di-0S, delta Di-6S, delta Di-4S, delta Di-diSE and delta Di-triS. These four types of periodontal tissue showed different molar ratios of the unsaturated disaccharides. The ratio of delta Di-4S to delta Di-6S was greater in the calcified than in the uncalcified tissue.
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PMID:High-performance liquid chromatography analysis of chondroitin sulfate isomers in human periodontium. 818 1

Postnatal expression of chondroitin sulfate proteoglycans was studied in the rat thalamus by immunocytochemistry and Western immunoblotting techniques with monoclonal antibodies that recognize carbohydrate epitopes (clones CS-56, 1-B-5, 2-B-6). The complex of the results shows that these antibodies recognize mostly nonoverlapping molecules whose expression is regulated during postnatal development. Chondroitin sulfate proteoglycans, recognized by antibody CS-56, and hyaluronan, identified by antibody 1-B-5 after hyaluronidase digestion, are abundant in the neuropil of most thalamic nuclei at the perinatal stage and progressively decrease during the second week of life, attaining levels barely detectable by immunocytochemistry at the end of the third week. In adult thalamus, chondroitin sulfate proteoglycans of high molecular mass, bearing glycosaminoglycans unsulfated in the linking region, and recognized by antibody 1-B-5 are confined to perineuronal nets around neurons chiefly localized in thalamic reticular nucleus. The immunoreactvity for antibody 2-B-6, specific for chondroitin-4-sulfate, is low at the perinatal stage and is not detectable in adult thalamus. Double-immunolabeling has shown that, along the rostrocaudal extension of reticular nucleus, the most developed perineuronal nets are associated with a subset of neurons expressing calretinin, and not with parvalbumin-positive neurons, which represent the largest neuronal population of the nucleus. The distribution of perineuronal nets supports the presence, in thalamic reticular nucleus, of neuronal subpopulations with different morphological and physiological features.
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PMID:Chondroitin sulfate proteoglycans in the rat thalamus: expression during postnatal development and correlation with calcium-binding proteins in adults. 1168 76

Chondroitin sulphate, fibronectin, laminin and the hyaluronan receptor, CD44, were localized in ovine skin during follicle morphogenesis. Prior to initiation, chondroitin sulphate was detected in the mesenchyme adjacent to the dermal-epidermal junction and showed an approximately regular periodicity in staining intensity. With the appearance of follicle primordia, the more strongly stained regions of the matrix were associated with mesenchymal condensations. During later development and in the mature follicle, staining was localized to the matrices of cells of the dermal sheath and papilla. CD44 was also localized in the mesenchymal condensations at follicle initiation and, subsequently, in the dermal sheath. Fibronectin staining was confined to the mesenchyme prior to follicle formation and became associated with presumptive papilla and dermal sheath cells during follicle formation and maturation. Fibronectin antisera detected an approximately 220 kDa protein in western blots of adult and fetal skin. An additional band of 150 kDa was also observed prior to follicle initiation. In contrast, laminin was predominantly restricted to the basal laminae of developing and mature follicles. The aggregative behaviour of ovine papilla cells was examined in vitro. The number and size of aggregates were not affected by inclusion of chondroitin sulphate or fibronectin in the culture medium, but both increased in the presence of hyaluronidase. Chondroitinase had the opposite effect and beta-D-xyloside completely abolished aggregative behaviour. In conclusion, the appearance of certain matrix molecules may presage morphogenetic movements of cells at follicle initiation and regulate patterns of follicle distribution in skin during fetal life.
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PMID:Extracellular matrix molecules and follicle morphogenesis in ovine skin. 1172 Jan 31

Chondroitin sulfate proteoglycan (CS-PG) expression is increased in response to CNS injury and limits the capacity for axonal regeneration. Previously we have shown that neurocan is one of the CS-PGs that is upregulated (Asher et al., 2000). Here we show that another member of the aggrecan family, versican, is also upregulated in response to CNS injury. Labeling of frozen sections 7 d after a unilateral knife lesion to the cerebral cortex revealed a clear increase in versican immunoreactivity around the lesion. Western blot analysis of extracts prepared from injured and uninjured tissue also revealed considerably more versican in the injured tissue extract. In vitro studies revealed versican to be a product of oligodendrocyte lineage cells (OLCs). Labeling was seen between the late A2B5-positive stage and the O1-positive pre-oligodendrocyte stage. Neither immature, bipolar A2B5-positive cells, nor differentiated, myelin-forming oligodendrocytes were labeled. The amount of versican in conditioned medium increased as these cells differentiated. Versican and tenascin-R colocalized in OLCs, and coimmunoprecipitation indicated that the two exist as a complex in oligodendrocyte-conditioned medium. Treatment of pre-oligodendrocytes with hyaluronidase led to the release of versican, indicating that its retention at the cell surface is dependent on hyaluronate (HA). In rat brain, approximately half of the versican is bound to hyaluronate. We also provide evidence of a role for CS-PGs in the axon growth-inhibitory properties of oligodendrocytes. Because large numbers of OLCs are recruited to CNS lesions, these results suggest that OLC-derived versican contributes to the inhospitable environment of the injured CNS.
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PMID:Versican is upregulated in CNS injury and is a product of oligodendrocyte lineage cells. 1189 62

Chondroitin sulfate, a glycosaminoglycan that is widely distributed among mammals, is used as a therapeutic agent in various diseases. Here, we focus on its absorption, excretion and tissue accumulation in rats. The concentration of 35S-chondroitin sulfate (35S-CS) in plasma reaches a peak in the first 5 min after intravenous administration and simultaneously increases in the urine. Approximately 25% of the 35S found in the urine appears as inorganic sulfate, indicating that 35S-CS is partially degraded during its renal filtration. The glycosaminoglycan is retained mainly by the liver and the kidney, where the amount of 35S reaches a plateau in the first 30 min, remains constant up to 2 h and then decreases markedly. Renal filtration and organ accumulation of 35S-CS decreases as the size of the glycosaminoglycan is reduced, especially in the liver. A derivative of 35S-CS that resists hyaluronidase digestion due to reduction of its glucuronic acid carboxyl groups appears at lower concentrations in plasma and in urine when compared with native 35S-CS. This derivative reaches higher levels in the kidney but lower levels in the liver when compared with the native molecule. Overall, our results indicate a balance between renal and hepatic mechanisms for removing chondroitin sulfate from plasma. The renal filtration increases as the molecular weight of the glycosaminoglycan decreases, whereas hepatic removal requires structural integrity and the presence of high-molecular-weight chains.
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PMID:Effects of molecular size and chemical structure on renal and hepatic removal of exogenously administered chondroitin sulfate in rats. 1654 12

Chondroitin sulfate (CS) chains are involved in the regulation of various biological processes. However, the mechanism underlying the catabolism of CS is not well understood. Hyaluronan (HA)-degrading enzymes, the hyaluronidases, are assumed to act at the initial stage of the degradation process, because HA is similar in structure to nonsulfated CS, chondroitin (Chn). Although human hyaluronidase-1 (HYAL1) and testicular hyaluronidase (SPAM1) can degrade not only HA but also CS, they are assumed to digest CS to only a limited extent. In this study, the hydrolytic activities of HYAL1 and SPAM1 toward CS-A, CS-C, Chn, and HA were compared. HYAL1 depolymerized CS-A and HA to a similar extent. SPAM1 degraded CS-A, Chn, and HA to a similar extent. CS is widely distributed from very primitive organisms to humans, whereas HA has been reported to be present only in vertebrates with the single exception of a mollusk. Therefore, a genuine substrate of hyaluronidases appears to be CS as well as HA.
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PMID:Hyaluronidases Have Strong Hydrolytic Activity toward Chondroitin 4-Sulfate Comparable to that for Hyaluronan. 2497 Jan 49

Chondroitin sulfate (CS) is a linear acidic polysaccharide composed of repeating disaccharide units of glucuronic acid and N-acetyl-d-galactosamine. The polysaccharide is modified with sulfate groups at different positions by a variety of sulfotransferases. CS chains exhibit various biological and pathological functions by interacting with cytokines and growth factors and regulating their signal transduction. The fine structure of the CS chain defines its specific biological roles. However, structural analysis of CS has been restricted to disaccharide analysis, hampering the understanding of the structure-function relationship of CS chains. Here, we chemo-enzymatically synthesized CS dodecasaccharides having various sulfate modifications using a bioreactor system of bacterial chondroitin polymerase mutants and various CS sulfotransferases. We developed a sequencing method for CS chains using the CS dodecasaccharides. The method consists of (i) labeling a reducing end with 2-aminopyridine (PA), (ii) partial digestion of CS with testicular hyaluronidase, followed by separation of PA-conjugated oligosaccharides with different chain lengths, (iii) limited digestion of these oligosaccharides with chondroitin lyase AC II into disaccharides, followed by labeling with 2-aminobenzamide, (iv) CS disaccharide analysis using a dual-fluorescence HPLC system (reversed-phase ion-pair and ion-exchange chromatography), and (v) estimation of the composition by calculating individual disaccharide ratios. This CS chain sequencing allows characterization of CS-modifying enzymes and provides a useful tool toward understanding the structure-function relationship of CS chains.
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PMID:Sequence determination of synthesized chondroitin sulfate dodecasaccharides. 2679 44


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