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

Urinary trypsin inhibitor (UTI) inhibits not only tumor cell invasion but also production of experimental and spontaneous metastasis. Cell-binding experiments indicated that human choriocarcinoma SMT-cc1 cells have specific binding sites for UTI on their cell surface. [Kobayashi et al., J. Biol. Chem. 269, 1994, 20,642-20,647]. UTI binding protein (UTIBP) was purified to homogeneity by a combination of UTI-coupled affinity beads, preparative polyacrylamide gel electrophoresis and reverse phase HPLC. This protein is very similar to a truncated form of human cartilage link protein (LP). LP was identified structurally by its apparent molecular mass with and without deglycosylation treatment: Immunologically by the reactivity with anti-UTIBP antibody, and functionally by its ability to bind the NH2-terminal domain of UTI. UTI and UTIBP are distributed uniformly in the cytoplasm and/or over the cell surface of tumor cells and fibroblasts. The level of staining for hyaluronic acid, UTIBP and UTI is much lower in sections digested with hyaluronidase. These results suggest that the cell membrane-derived UTI-associated binding protein is the LP of proteoglycan-hyaluronic acid aggregates, which interacts with hyaluronic acid. Cell-associated LP may play a role in modulating protease activity to the environment close to tumor and fibroblast cell surface.
 ...
PMID:Identification and characterization of the cell-associated binding protein for urinary trypsin inhibitor. 960 43

Cumulus oocyte complex (COC) expansion is induced through hyaluronic acid production and accumulation of proteins of the inter-alpha-trypsin inhibitor family in the gonadotropin-stimulated cumulus cells. Link protein, a glycoprotein found in cartilage, interacts specifically with hyaluronic acid and stabilizes the binding of proteoglycan monomers to hyaluronic acid to form aggregates. The aim of this study was to investigate the expression of immunoreactive link protein during follicle development in rats and in cumulus cells in culture by immunohistochemistry and Western blot as well as by specific enzyme-linked immunosorbent assay. Immunohistochemical analysis revealed that the extracellular matrix of cumulus cells that were morphologically at a stage of COC expansion were markedly stained for link protein, whereas granulosa cells from immature follicles were not stained. Cumulus cells deposited link protein into the extracellular matrix in an in vitro culture system. The staining intensity was negated by the treatment with hyaluronidase, suggesting that the link protein is bound to hyaluronic acid. We have identified a 42-kDa immunoreactive link protein in rat ovary during the preovulatory period and in COC extracts. Addition of FSH to the medium of cumulus cells in culture supplemented with 10% FBS and oocyte-conditioned medium resulted in an increased rate of link protein synthesis. This work suggests that the cumulus cells synthesize the link protein that may stabilize the binding of inter-alpha-trypsin inhibitor or dermatan sulfate proteoglycan to hyaluronic acid to make up hyaluronic acid-rich matrix aggregate.
 ...
PMID:Identification of link protein during follicle development and cumulus cell cultures in rats. 1043 45

We have observed that the spent culture media in suspended chondrocyte cultures is essential for the survival of the cells, since complete change of the spent media induces severe programmed cell death (apoptosis). Moreover, we showed that extracellular matrix (ECM) molecules in the culture media provide vital chondrocyte-matrix interactions; when media are changed, cells are deprived of matrix molecules and undergo apoptosis. In this paper we report that interaction with collagen, a ubiquitous extracellular matrix molecule, is essential for chondrocyte survival. Such an interaction causes chondrocyte aggregation and reduces the level of chondrocyte apoptosis. Hyaluronan, an abundant ECM molecule, can influence the effects of collagen by preventing chondrocyte aggregation. Degradation of hyaluronan with hyaluronidase results in chondrocyte aggregation, and this reduces the level of chondrocyte apoptosis. Experiments with an antibody to integrin beta1 suggest that the collagen-chondrocyte interactions are mediated through integrin beta1, and these interactions may protect chondrocytes from apoptosis. We hypothesize that hyaluronan binds aggrecan and link protein, forming stable ternary complexes, which interact with the chondrocyte surface, perhaps via CD44, and thus maintains a stable chondrocyte-matrix network.
 ...
PMID:beta-Integrin-collagen interaction reduces chondrocyte apoptosis. 1051 81

To gain insight into the role of link protein in ovarian follicle development, we used immunohistochemistry to determine the patterns of link protein expression in mouse ovary in response to gonadotropin stimulation. Polyclonal antibodies were raised against link protein purified from bovine cartilage. Stimulation of immature mice with gonadotropins increased link protein expression in the granulosa layer of large preovulatory follicles. The number and intensity of immunostained cells increased over 2 hr after hCG injection. Cumulus cells stained link protein mainly in the extracellular matrix, whereas mural granulosa cells showed marked deposits of link protein in the cytoplasm. Link protein expression persisted in luteinized granulosa cells after ovulation and in corpora lutea. Link protein staining was also present in the theca cells and oocytes, which was a consistent finding regardless of gonadotropin treatment. The staining intensity was negated by treatment with hyaluronidase, suggesting that the link protein is bound to hyaluronic acid. On Western blotting, a reacting protein species of about 42 kD was seen in the gonadotropin-treated ovarian extract. The precise cellular distribution of link protein in mouse ovary was determined for the first time by an immunohistochemical method in this study. (J Histochem Cytochem 47:1433-1442, 1999)
 ...
PMID:Expression of link protein during mouse follicular development. 1054 16

The most abundant macromolecules in cartilage are hyaluronan, collagen, aggrecan, and link protein, which are believed to play roles in maintaining a unique three-dimensional network for a functional joint. This study was designed to investigate the roles of the major extracellular molecules in mediating chondrocyte-matrix interactions. We employed specific approaches to remove components individually or in combination: hyaluronan was digested with hyaluronidase; type II collagen was digested with collagenase; aggrecan expression was inhibited with antisense and beta-xyloside approaches; and link protein expression was inhibited with antisense oligonucleotides. Digestion of hyaluronan induced chondrocyte attachment to tissue culture plates, collagen-coated plates, and fibroblast-like chondrocyte cultures, and induced chondrocyte aggregation. Treated chondrocytes exhibited a fibroblast-like morphology, and the effects of hyaluronidase were dose-dependent. Conversely, the effect of collagenase on chondrocyte adhesion and aggregation was far less pronounced. Treatment with Arg-Gly-Asp peptide inhibited chondrocyte-collagen interaction. Chondrocyte attachment was enhanced by antisense oligonucleotides complementary to aggrecan and link protein and by beta-xyloside treatment. Nevertheless, hyaluronan seems to predominate over the other molecules in mediating chondrocyte-matrix interactions.
 ...
PMID:The roles of matrix molecules in mediating chondrocyte aggregation, attachment, and spreading. 1096 59

Hyaluronan synthesized in the epidermis has an exceptionally short half-life, indicative of its catabolism by epidermal keratinocytes. An intracellular pool of endogenously synthesized hyaluronan, from 1 to 20 fg/cell, inversely related to cell density, was observed in cultured rat epidermal keratinocytes. More than 80% of the intracellular hyaluronan was small (<90 kDa). Approximately 25% of newly synthesized hyaluronan was endocytosed by the keratinocytes and had a half-life of 2-3 h. A biotinylated aggrecan G(1) domain/link protein probe demonstrated hyaluronan in small vesicles of approximately 100 nm diameter close to the plasma membrane, and in large vesicles and multivesicular bodies up to 1300 nm diameter around the nucleus. Hyaluronan did not co-localize with markers of lysosomes. However, inhibition of lysosomal acidification with NH(4)Cl or chloroquine, or treating the cells with the hyaluronidase inhibitor apigenin increased intracellular hyaluronan staining, suggesting that it resided in prelysosomal endosomes. Competitive displacement of hyaluronan from surface receptors using hyaluronan decasaccharides, resulted in a rapid disappearance of this endosomal hyaluronan (t(12) approximately 5 min), indicating its transitory nature. The ultrastructure of the hyaluronan-containing vesicles, co-localization with marker proteins for different vesicle types, and application of specific uptake inhibitors demonstrated that the formation of hyaluronan-containing vesicles did not involve clathrin-coated pits or caveolae. Treatment of rat epidermal keratinocytes with the OX50 monoclonal antibody against the hyaluronan receptor CD44 increased endosomal hyaluronan. However, no CD44-hyaluronan co-localization was observed intracellularly unless endosomal trafficking was retarded by monensin, or cultivation at 20 degrees C, suggesting CD44 recycling. Rat epidermal keratinocytes thus internalize a large proportion of their newly synthesized hyaluronan into non-clathrin-coated endosomes in a receptor mediated way, and rapidly transport it to slower degradation in the endosomal/lysosomal system.
 ...
PMID:Hyaluronan enters keratinocytes by a novel endocytic route for catabolism. 1145 52

The aim of this study was to localise hyaluronan (HA)-binding proteins (HABPs) in ovine vertebral tissues using biotinylated HA oligosaccharides (bHA oligos) as novel affinity probes and to compare this with the distribution of tissue HA visualised using biotinylated aggrecan G1 domain-link protein complex. The bHA oligos, with a size of 6-18 disaccharides were prepared by partial digestion of HA with ovine testicular hyaluronidase, labelled with biotin hydrazide and purified by a combination of aggrecan G1 domain and avidin affinity chromatography. Hyaluronan and HABPs were both prominent pericellular components of hypertrophic cells of the vertebral epiphyseal growth plate and enlarged cells in the cartilaginous end plate of the disc. The bHA oligo probe also visualised HABPs intracellularly in hypertrophic cells, which also contained intracellular HA. Monolayer cultures of ovine annulus fibrosus and nucleus pulposus cells rapidly internalised the bHA oligo affinity probe which was subsequently visualised by indirect fluorescence using avidin-FITC, to cytoplasm and discrete nuclear regions. The results indicate that the abundant pericellular and intracellular HA associated with cartilaginous cells in the vertebral tissues is colocalised with HABPs. The bHA oligo affinity probe may have further applications in investigations of intracellular HABPs, HA endocytosis and the roles they play in cellular regulatory processes.
 ...
PMID:Visualisation of hyaluronan and hyaluronan-binding proteins within ovine vertebral cartilages using biotinylated aggrecan G1-link complex and biotinylated hyaluronan oligosaccharides. 1197 5

The relative contribution of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4 and ADAMTS5 to aggrecan degradation under oncostatin M (OSM) stimulation, the role of the ancillary domains of the aggrecanases on their ability to cleave within the chondroitin sulfate (CS)-2 region, the role of hyaluronidases (HYAL) in stimulating aggrecan release in the absence of proteolysis, and the identity of the hyaluronidase involved in OSM-mediated cartilage breakdown were investigated. Bovine articular cartilage explants were cultured in the presence of interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha) and/or OSM, or treated with trypsin and/or hyaluronidase. Aggrecan was digested with various domain-truncated isoforms of ADAMTS4 and ADAMTS5. Aggrecan and link protein degradation and release were analyzed by immunoblotting. Aggrecanase and HYAL gene expression were determined. ADAMTS4 was the most inducible aggrecanase upon cytokine stimulation, whereas ADAMTS5 was the most abundant aggrecanase. ADAMTS5 was the most active aggrecanase and was responsible for the generation of an OSM-specific degradation pattern in the CS-2 region. Its ability to cleave at the OSM-specific site adjacent to the aggrecan G3 region was enhanced by truncation of the C-terminal thrombospondin domain, but reduced by further truncation of both the spacer and cysteine-rich domains of the enzyme. OSM has the ability to mediate proteoglycan release through hyaluronan degradation, under conditions where HYAL-2 is the predominant hyaluronidase being expressed. Compared to other catabolic cytokines, OSM exhibits a unique potential at degrading the proteoglycan aggregate, by promoting early robust aggrecanolysis, primarily through the action of ADAMTS5, and hyaluronan degradation.
 ...
PMID:Involvement of ADAMTS5 and hyaluronidase in aggrecan degradation and release from OSM-stimulated cartilage. 2122 93


<< Previous 1 2