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)

A high molecular weight secretion product of cell lines established from duct cell-derived human pancreatic adenocarcinomas was investigated in this study. After metabolic labeling and molecular sieve chromatography of culture medium, a product appeared in the void volume of a Superose 6 column that could be labeled with [3H]glucosamine, but not with [35S]sulfate. After further purification by anion exchange chromatography it was analyzed and demonstrated to be hyaluronan (HA). CsCl density gradient centrifugation revealed a density of 1.45 g/cm3 in a 4 M guanidinium hydrochloride solution. [3H]Glucosamine-labeled material could be degraded by digestion with hyaluronidase from two sources, but not with heparitinase I or chondroitinase AC. Sugar analysis revealed glucuronic acid and glucosamine at a molar ratio of 1:1. When the amount of HA synthesized by different pancreatic adenocarcinoma cell lines was compared, the values of the cell lines PaTu 8902 and PaTu II were about five- to tenfold higher than those of the lines PaTu 8988s, PaTu 8988t or HPAF, but an order of magnitude lower than in murine 3T3 fibroblasts. HA synthesis per cell decreased with increasing cell density. In serum-free cultures of cell lines with high HA synthesis it was 3 to 5 times higher compared to cultures that were supplemented with serum. We conclude that pancreatic adenocarcinoma cells secrete hyaluronan and thus contribute to the extracellular matrix of the tumor tissue. In pancreatic carcinoma cells, regulation of HA biosynthesis seems not to be positively correlated to proliferation as has been demonstrated for fibroblasts.
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PMID:Hyaluronan is a secretory product of human pancreatic adenocarcinoma cells. 164 63

We have recently shown that the large hyaluronan-aggregating chondroitin sulfate proteoglycan from cartilage (PG-LA) is unfavorable as a substrate for neural crest cell migration in vitro and that this macromolecule inhibits cell dispersion on fibronectin substrates when included in the medium (R. Perris and S. Johansson, 1987, J. Cell Biol. 105, 2511-2521). In this study we present data on the specificity of the migration-repressing activity of PG-LA and data on the molecular mechanisms by which the proteoglycan might impair neural crest cell motility. Soluble PG-LA potently impaired cell migration on substrates of laminin/laminin-nidogen, vitronectin, and collagen types I, III, IV, and VI. When tested in solid-phase binding assays, PG-LA bound avidly to substrates of collagen types I-III and V. Conversely, minimal amounts of the proteoglycan bound to substrates of laminin-nidogen, vitronectin, collagen types IV and VI, and fibronectin or to a proteolytic fragment encompassing its cell-binding domain (105 kDa). Preincubation of these substrates with soluble PG-LA prior to plating of the cells had no effect on their locomotory behavior. These results indicate that PG-LA affects neural crest cell movement primarily through an interaction with the cell surface, rather than by association with the cell motility-promoting substrate molecules. The molecular interaction of soluble PG-LA with neural crest cells was further examined by analyzing the effects of isolated domains of the proteoglycan on cell migration on fibronectin. Addition of chondroitin sulfate chains, the core protein free of glycosaminoglycans, the isolated hyaluronan-binding region (HABr), or a proteolytic fragment corresponding to the keratan sulfate-enriched domain of the PG-LA to neural crest cells migrating on fibronectin or the 105-kDa fibronectin fragment had no significant effect on their motility. After reduction and alkylation, PG-LA was considerably less efficient in perturbing cell movement on fibronectin substrates and virtually ineffective in altering migration on the 105-kDa fragment. In the presence of hyaluronan fragments of 16-30 monosaccharides in length, or an antiserum against the HABr, the migration repressing activity of PG-LA was reduced in a dose-dependent fashion. Furthermore, the inhibitory action of PG-LA was significantly reduced by treatment of the cells with Streptomyces hyaluronidase.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Inhibition of neural crest cell migration by aggregating chondroitin sulfate proteoglycans is mediated by their hyaluronan-binding region. 168 36

Rapid intravenous (iv) infusion of protamine sulfate is associated with hypotension in humans. A possible mechanism for this hypotension is the release of inflammatory mediators, including histamine, from tissue mast cells lining the blood vessels. To determine whether protamine caused nonimmunologic release of histamine, histamine released from dispersed human skin mast cells exposed to protamine sulfate was measured. Skin from seven adult patients was washed, chopped into small tissue fragments, and incubated with collagenase, hyaluronidase, and DNAase. Dispersed mast cells were harvested after 12 h of short-term tissue culture, washed, and challenged with protamine sulfate. Histamine release was measured using an automated histamine analyzer and expressed as a per cent of total released histamine measured minus the spontaneous histamine release. Spontaneous histamine release averaged 6 +/- 1%. Protamine produced dose-related histamine release. At a concentration of 3 X 10(-3) M, protamine sulfate released 14 +/- 2% (P less than 0.05), which significantly differed from spontaneous release. This study demonstrates that protamine sulfate causes nonimmunologic histamine release in dispersed human skin mast cells. However, histamine release occurred only at concentrations much greater than those used in clinical practice. Thus, these data do not support the hypothesis that nonimmunologic histamine release is a likely mechanism for protamine-induced hypotension in vivo.
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PMID:Protamine-induced histamine release in human skin mast cells. 169 14

Intratracheal instillation of bleomycin in hamsters initiates a series of events that mimic human interstitial pulmonary fibrosis. Because glycosaminoglycans and particularly hyaluronan (hyaluronic acid, HA), may play an important role in the extracellular matrix response to early injury and subsequent fibrosis, this study was undertaken to define the early time course of changes in HA and hyaluronidase. Hamsters were given either 1 unit bleomycin sulfate in 0.2 ml saline or 0.2 ml saline (control), and randomly selected animals from both groups were killed at Days 3, 5, 6, 7, 9, and 17. Glycosaminoglycan fractions prepared from lung tissue of individual animals were analyzed for HA. The maximal HA content was reached 6 days after instillation of bleomycin and was 14.6-fold the normal value. The weight of injured lungs was 2.3-fold the control value. Thus, the increase in HA content was 30-fold. By Day 7 the HA content had dropped sharply. It then declined gradually to approximately double control values at Day 17. The specific activity of lysosomal hyaluronidase was the same in bleomycin-treated lungs and control lungs. Total units of the enzyme were increased in injured lungs, even at the time of maximal HA content, indicating active turnover of HA. The maximal HA content occurs prior to the rise in collagen and elastin biosynthesis. This observation in addition to the magnitude of the increase and its abrupt decline suggest that HA may be an important initiating factor for pathologic changes in lung extracellular matrix components.
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PMID:Early changes in lung tissue hyaluronan (hyaluronic acid) and hyaluronidase in bleomycin-induced alveolitis in hamsters. 170 35

Hyaluronan (HA) and one of its cell binding sites, fibroblast hyaluronan binding protein (HABP), is shown to contribute to the regulation of 10T1/2 cell locomotion that contain an EJ-ras-metallothionein (MT-1) hybrid gene. Promotion of the ras-hybrid gene with zinc sulfate acutely stimulates, by 6-10-fold, cell locomotion. After 10 h, locomotion drops to two- to threefold above that of uninduced cells. Several observations indicate increased locomotion is partly regulated by HA. These include the ability of a peptide that specifically binds HA (HABR) to reduce locomotion, the ability of HA (0.001-0.1 micrograms/ml), added at 10-30 h after induction to stimulate locomotion back to the original, acute rate, and the ability of an mAb specific to a 56-kD fibroblast HABP to block locomotion. Further, both HA and HABP products are regulated by induction of the ras gene. The effect of exogenous HA is blocked by HABR, is dose-dependent and specific in that chondroitin sulfate or heparan have no significant effect. Stimulatory activity is retained by purified HA and lost upon digestion with Streptomyces hyaluronidase indicating that the activity of HA resides in its glycosaminoglycan chain. Uninduced cells are not affected by HA, HABR, or mAb and production of HA or HABP is not altered during the experimental period. These results suggest that ras-transformation activates an HA/HABP locomotory mechanism that forms part of an autocrine motility mechanism. Reliance of induced cells on HA/HABP for locomotion is transient and specific to the induced state.
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PMID:Hyaluronan and a cell-associated hyaluronan binding protein regulate the locomotion of ras-transformed cells. 170 59

Conditioned medium from Sertoli cells, prepared from testes of 20-day-old rats, contains component(s) that inhibit the incorporation of [3H]-thymidine into DNA of peritubular myoid cells (PMC) and inhibit the proliferation of PMC. These components are trypsin-resistant, heat-stable compounds having a molecular weight less than 30,000. The active inhibitory components in Sertoli cell conditioned medium are inactivated by treatment with heparinase, but not by treatment with hyaluronidase or chondroitin sulfate lyases. Addition of heparin or heparan sulfate results in inhibition of DNA synthesis by PMC in a dose-dependent manner, whereas other glycosaminoglycans (GAGs) examined (hyaluronic acid, keratan sulfate, and chondroitin sulfate) have no detectable effects. Heparin and heparan sulfate are unique among GAGs tested in inhibiting the characteristic multilayer growth pattern of PMC following the attainment of confluence in serum-rich medium. On the basis of these and other data presented, it is concluded that heparin and other heparin-like GAGs synthesized by Sertoli cells are implicated in the modulation of growth of PMC in vitro during co-culture. It is postulated that heparin may play a similar role in maintaining the quiescent peritubular myoid cell phenotype in vivo.
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PMID:Sertoli cells in culture secrete paracrine factor(s) that inhibit peritubular myoid cell proliferation: identification of heparinoids as likely candidates. 171 60

Chondrons have recently been extracted from adult articular cartilages and techniques developed to study their structure and composition in isolation. This study introduces methods to immobilize isolated canine chondrons in thin layers of agarose gel for immunohistochemistry and future in vitro studies. An antibody to Type VI collagen which stained the chondron in suspension was used to successfully validate the system and its feasibility for immunoelectron microscopy. Monoclonal and polyclonal antibodies to a variety of epitopes on the proteoglycan molecule were tested on fresh and fixed plugs cored from chondron-agarose gels. Plugs were immunolabeled with peroxidase-diaminobenzidine before or after digestion with testicular hyaluronidase or chondroitinase ABC. Trypsin/chymotrypsin were used to challenge epitopes of the core protein. The results indicate that epitopes to keratan sulfate, chondroitin sulfate, hyaluronate binding region, and core protein are localized in the chondron. Consistent staining was found in the tail and interconnecting segments between chondrons, whereas staining of the pericellular matrix and capsule adjacent to the chondrocyte varied according to the enzyme pre-treatment employed. We conclude that isolated chondrons are rich in proteoglycan monomer, which is particularly concentrated in the tail and interconnecting segments of the chondron where it could function to protect and stabilize the chondrocyte.
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PMID:Chondrons from articular cartilage. (IV). Immunolocalization of proteoglycan epitopes in isolated canine tibial chondrons. 171 45

Mammalian spermatozoa and seminal plasma both contain high levels of arylsulfatases (AS), enzymes that remove sulfate from sulfated glycoconjugates. In ejaculated semen of boars, 85% of AS was found in seminal plasma whereas only 13% was found in spermatozoa. A comparable distribution of AS between spermatozoa and seminal plasma was observed in other domestic mammals. The presence of AS in seminal plasma was not due to leakage from spermatozoa because sperm cells had intact acrosomes and plasma membranes after their separation from seminal plasma, and because 84% of the acrosomal marker enzyme hyaluronidase was retained in washed spermatozoa. Spermatozoa in boar semen diluted with Beltsville Thawing Solution (BTS) deteriorated faster during storage at 17 degrees C than spermatozoa stored in BTS without seminal plasma. This suggests that seminal plasma has a deleterious effect on mammalian spermatozoa. We propose that (1) sulfated glycoconjugates stabilize sperm plasma membranes; (2) AS present in seminal plasma contribute to the deterioration of spermatozoa by desulfating these glycoconjugates; and (3) AS present in seminal plasma could well play a role in sperm capacitation.
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PMID:Arylsulfatases are present in seminal plasma of several domestic mammals. 178 86

Lysosomal hyaluronidase is responsible for the degradation of hyaluronan, a component of the extracellular matrix, in degenerative disorders of the joints. It has been hypothesized that the administration of chondroitin sulfate (both a component of the extracellular matrix and a substrate for hyaluronidase) could compete for this enzyme and reduce the degradation process. The present study shows that a mixture of chondroitin 4-sulfate and chondroitin 6-sulfate is a good competitor of hyaluronan for hyaluronidase. The digestion of hyaluronan is reduced in proportion to the amount of competing chondroitin. The competitive ability is dependent on the 4-sulfate, 6-sulfate composition of the chondroitin mixture. Mixtures richer in the 4-sulfate isomer are more effective. The enzymatic reactions have been monitored by HPLC and PAGE.
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PMID:Chondroprotective action of chondroitin sulfate. Competitive action of chondroitin sulfate on the digestion of hyaluronan by bovine testicular hyaluronidase. 181 45

The hydraulic conductivity of pulmonary interstitium was measured in a short isolated segment of interstitium surrounding a large pulmonary artery (1-3 mm diam) of the rabbit. The flow rate of the following solutions was measured sequentially: normal saline, polycation protamine sulfate (0.08 mg/ml), cationic dextran (0.1 or 1.5%) or anionic dextran (0.1 or 1.5%), and hyaluronidase (testes, 0.02%) solution. The pH of all solutions was adjusted to 7.35-7.40. The ratios of the flow of protamine sulfate and cationic dextran to that of saline averaged 2.3 +/- 0.92 (SD, n = 7) and 3.0 +/- 1.2 (n = 6), respectively. The anionic dextran-to-saline flow ratio averaged 0.72 +/- 0.28 (n = 13). Flow increased in the presence of positively charged molecules and decreased in the presence of negatively charged molecules. At a lower pH of 5.0-6.0, only 0.1% cationic dextran had an effect on interstitial conductivity. Thus pulmonary interstitium at physiological pH has the properties of a negatively charged membrane. The increased interstitial conductivity caused by the positively charged molecules was not observed after treatment with hyaluronidase. These effects of electric charge on interstitial conductivity were partly attributed to the presence in the interstitium of negatively charged hyaluronan.
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PMID:Effects of electric charge on hydraulic conductivity of pulmonary interstitium. 186 72


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