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:3.2.1.36 (hyaluronidase)
4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyaluronan, a glucosaminoglycan with unique water-binding capacity, is accumulated in the interstitial edematous tissue in rejecting organs. We here investigated whether the increased tissue content of water and hyaluronan seen during allograft rejection can be prevented by treatment with the hyaluronan-degrading enzyme hyaluronidase. Heterotopic heart transplantations between PVG and Wistar/Kyoto rats were performed. Recipient rats were treated with hyaluronidase prophylactically or therapeutically, either alone or in combination with cyclosporine. Daily intravenous injections of hyaluronidase induced a significant reduction of the cardiac content of both hyaluronan and water, as evaluated on day six after transplantation. Morphological examination revealed grafts with better preserved morphology and fewer infiltrating mononuclear cells, compared to untreated controls. Hyaluronidase therapy, alone or combined with cyclosporine, resulted in prolonged graft survival times. Hyaluronidase infusion for two hours also reduced already established edema five days after transplantation. This study confirms the hypothesis that hyaluronan accumulation plays a critical role in edema formation, and that hyaluronidase therapy can be used to reduce edema after organ transplantation.
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PMID:Hyaluronidase ameliorates rejection-induced edema. 1046 Aug 67

Albumin diffusion measured in an isolated segment of rabbit lung interstitium with a radioactive tracer ((125)I-albumin) technique was independent of albumin concentration and similar to the free diffusion of albumin in water (Qiu et al, 1998. J Appl Physiol 85: 575-583). We studied the effect of hyaluronidase on the diffusion of albumin. Isolated rabbit lungs were inflated with silicon rubber by way of airways and blood vessels, and two chambers were bonded to the sides of a approximately 0.5-cm thick slab enclosing a vessel with an interstitial cuff. One chamber was filled with 2 g/dl albumin solution containing (125)I-albumin and 0.02 g/dl hyaluronidase. Unbound (125)I was removed from the tracer by dialysis before use. The other chamber filled with Ringer's solution was placed within a NaI(Tl) scintillation detector. Diffusion of tracer was measured continuously for 120 h. Albumin diffusion coefficient (D) and interstitial area (A) were obtained by fitting the tracer-time curve with the theoretical solution of the equation describing one-dimension diffusion of a solute across a membrane. D averaged 5.2 x 10(-7) cm(2)/s for albumin diffusion with hyaluronidase, 20% less than that measured previously without hyaluronidase. Hyaluronidase had no effect on A. Results indicated an interaction between albumin and interstitial hyaluronan that was the opposite of the steric effect on albumin excluded volume measured in solution.
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PMID:Effect of hyaluronidase on albumin diffusion in lung interstitium. 1046 20

Involvement of enzymes catabolizing hyaluronic acid (hyaluronidase, beta-glucuronidase, N-acetyl-beta-D-hexosaminidase) in the hydroosmotic action of vasopressin on the amphibian urinary bladder Rana Ridibunda was studied. It was found that vasopressin (50 nM), agonist of V2 receptors dDAVP (1.5 mcM) and forscolin (30 mcM) induce an activation of enzymes and its release into the Ringer solution at the mucosal surface simultaneously with the increase in the osmotic water flow. Maximal effect was observed 10 min later than hydroosmotic response. Release of enzymes under vasopressin effect was found in the absence of osmotic gradient and water flow through the epithelium. The repeated substitution of the outer Ringer solution for the fresh one resulted in the increase in the both the water permeability and the release of enzymes through the mucosal surface. We suggested that involvement of hyaluronate-hydrolases in the vasopressin effect is mediated by the cAMP-dependent mechanism. It is supposed that this effect creates conditions for the increase in the permeability of glycosaminoglycan structures covering adjacent to the apical cell surface.
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PMID:[Hyaluronate-hydrolases system and hydroosmotic effect of vasopressin]. 1051 5

Glycoprotein showing inhibitory activity against mast cell degranulation and hyaluronidase activity was purified from the hot water extract of mint plant (Perilla frutescens Britton). The purified inhibitor gave a single band detected with Coomassie brilliant blue staining and periodic acid-Schiff staining on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The molecular mass was estimated to be 6.0 kDa on SDS-PAGE. The inhibitor did not become inactivated when boiled for 30 min or digested with trypsin, V8 protease, or proteinase K but was inactivated by NaIO(4) oxidation. The inhibitor prevented mast cell degranulation and hyaluronidase activity (IC(50) = 0.42 mg/mL) in a dose-dependent manner. The inhibitor also inhibited the protein kinase C activity. It is possible to purify and characterize a glycoprotein with putative pharmacological properties from mint plants.
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PMID:Glycoprotein derived from the hot water extract of mint plant, Perilla frutescens britton. 1056 18

The importance of the interstitium and its major ground substance component, hyaluronan (HA), for solute and fluid transport across the peritoneal membrane has been debated during the last few years. We therefore partly removed HA from the peritoneal membrane using enzymatic digestion with hyaluronidase for 2 h, after which the transport properties of the peritoneal membrane were studied in peritoneal dialysis dwells. A dialysis fluid containing 3.86% glucose was used. As a marker of macromolecular transport, the total peritoneal clearance of radiolabelled albumin out of the peritoneal cavity and its clearance to plasma were measured, as well as the albumin clearance from plasma to dialysate. Transport of small solutes between plasma and dialysate was measured by assessing the mass transfer area coefficient of 51Cr-EDTA and glucose. Hyaluronidase preincubation yielded a 78% reduction of HA in the superficial layer of the peritoneal membrane, without alterations in the transport of either small or large solutes compared with the situation in preincubated controls. The only changes observed were between rats incubated with either hyaluronidase or vehicle alone compared to non-incubated controls. In conclusion, despite a large reduction of the HA content of the tissues surrounding the peritoneal cavity, hyaluronidase incubation did not produce any significant changes in solute and fluid transport across the peritoneal membrane. Our data indicate that peritoneal membrane HA in physiological concentrations plays a rather subordinate role in the overall transport of small solutes and water across the capillary-interstitial peritoneal barrier.
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PMID:Effects of peritoneal hyaluronidase treatment on transperitoneal solute and fluid transport in the rat. 1071 74

Diabetic patients have a greater incidence of restenosis, which has been shown to be related to exaggerated intimal hyperplasia. Hyaluronan (HA) has been shown to be closely involved in arterial smooth muscle cell proliferation and migration, which provoke intimal hyperplasia after balloon catheter injury. Our aim was to determine the effect of fructose feeding, which produces certain characteristics of non-insulin-dependent diabetes (ie, insulin resistance, hyperinsulinemia, and hypertriglyceridemia), on production of HA and hyaluronidase and degradation of HA in rat aorta. Treated rats received fructose (25% in tap water) 12 weeks before balloon catheter injury and 14 days afterward. Fructose-fed rats had hyperinsulinemia and hypertriglyceridemia. Injury increased intima-media wet weight (7.5%) and DNA content (20%) in control rats. This increase was significantly greater in fructose-fed rats (22% for wet weight and 34% for DNA content) and was associated with greater HA and hyaluronidase production (123% and 41%, respectively) than in control rats (49% and 7%, respectively). Determination of HA molecular mass showed that balloon catheter injury increased the number of HA fragments in the aorta of control rats. Normal aorta of fructose-fed rats contained more HA fragments than that of control rats. Injury to the aorta of fructose-fed rats increased HA fragments and induced the appearance of a very-high-molecular-mass (>2000 kDa) HA. In conclusion, fructose treatment, which induced hyperinsulinemia and hypertriglyceridemia, increased HA and hyaluronidase production and HA degradation in injured aorta. This finding suggests that HA, which has been shown to play a crucial role in proliferation and migration of arterial smooth muscle cells, may be involved in the promotional effect of long-term fructose feeding on arterial wall reaction to injury.
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PMID:Increased hyaluronan and hyaluronidase production and hyaluronan degradation in injured aorta of insulin-resistant rats. 1084 61

Electron microscopy of ultrathin sections stained with cationic iron colloid revealed that the rat pineal gland is provided with wide and intensely negative-charged pericapillary spaces. Light microscopically, the negative charging of the pericapillary spaces was completely eliminated by digestion with hyaluronidase and chondroitinase ABC. This pericapillary negative charging was also erased by digestion with collagenase. The results indicate that the negative charging is derived from sulfated proteoglycans which are bound to collagen molecules. These sulfated proteoglycans in the pericapillary spaces may retain numerous water molecules to form a tissue gel, and so act as a selective sieve regulating the passage of tissue molecules.
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PMID:Intensely negative-charged pericapillary spaces in the rat pineal gland. 1120 Dec 7

The involvement of enzymes catabolizing hyaluronic acid (hyaluronidase, beta-glucuronidase, N-acetyl-beta-D-hexosaminidase) in the hydroosmotic effect of vasopressin in the frog (Rana ridibunda) urinary bladder was studied. It was observed that vasopressin (50 nM), an agonist of V2 receptors, L-desamino-8-D-arginine-vasopressin (dDAVP, 1.5 microM) and forskolin (30 microM) activated the enzymes and caused their release into Ringer solution at the mucosal side, together with an increase in osmotic water flow. The effect of AVP on enzyme activity developed 10 min after the hydroosmotic response. Cytochalasin B (a specific inhibitor of actin filament elongation, 50 nM) blocked the hydroosmotic response to AVP; hyaluronate hydrolase activity increased in the bladder tissue but not in Ringer solution. It is suggested that the involvement of hyaluronate hydrolases in AVP's effect is mediated by a cAMP-dependent mechanism and provides favorable conditions for an increase in the permeability of glycosaminoglycan structures adjacent to the apical cell surface.
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PMID:Effects of vasopressin on hyaluronate hydrolase activities and water permeability in the frog urinary bladder. 1169 69

This study investigates the effects of aestivation on body water content, body mass, acid mucopolysaccharide (AMPS) and some of its degrading enzymes in different tissues for some Australian desert frogs. The AMPS component of the liver, kidney, skin and cocoon alter during aestivation to help retain water, which is unchanged in most tissues of all frog species, and to protect the frogs from desiccation during extended periods of aestivation. Hepatic AMPS was unaltered in Cyclorana maini, C. platycephala and Neobatrachus sutor but increased significantly after 2 months of aestivation in C. australis. The level of AMPS in the kidney was elevated in all four frog species after 5 months of aestivation. Skin AMPS content in the skin of awake frogs decreases with aestivation period and increases in the cocoon. AMPS in the cocoon probably works as a cement between the cocoons' layers and its physical presence presumably contributes to preventing water flux. Changes in AMPS content in different tissues were accompanied by significant changes in both hyaluronidase and beta-glucuronidase activities, which play an important role in AMPS metabolism. Alcian blue staining of control and digested skin of C. australis and C. platycephala with testicular hyaluronidase indicated the presence of AMPS, concentrated in a thin layer (called ground substance, GS) located between stratum compactum and stratum spongiosum, and acid mucin concentrated in the mucous glands and in a 'tubular' structure which could be observed in the epidermal layer. Hyaluronidase digestion of the cocoon slightly changed the Alcian Blue colour, suggesting the presence of a large amount of acid mucin similar to that found in the skin mucous gland. The results of this study present data for the redistribution of AMPS, which may help in reducing water loss across the cocoon and reabsorption of water in the kidney during aestivation.
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PMID:Water content, body weight and acid mucopolysaccharides, hyaluronidase and beta-glucuronidase in response to aestivation in Australian desert frogs. 1189 99

The action of hyaluronidase on oligosaccharides from hyaluronan is complicated due to branched reaction paths containing hydrolysis, transglycosylation and condensation. The unit component of hyaluronan is a disaccharide, namely GlcA-(beta 1-->3)-GlcNAc where GlcA and GlcNAc are d-glucuronic acid and d-N-acetylglucosamine respectively. Hyaluronan is the linear polymer formed by these disaccharide units, linked together with beta 1-->4 glycosidic bonds. Bovine testicular hyaluronidase acts only at beta 1-->4 glycosidic bonds of hyaluronan. The progress of product distribution from short oligosaccharides was simulated with the Monte Carlo method using the probabilistic model. The model consists only of a single enzyme molecule and a finite number of substrate and water molecules. The simulation is based on a simple reaction scheme and proceeds via an algorithm with minimum adjustable parameters generating random numbers and probabilities. The experimental data for bovine testicular hyaluronidase using [GlcA-(beta 1-->3)-GlcNAc](4) as the starting substrate were quantitatively simulated with only three adjustable parameters. The simulated data for [GlcA-(beta 1-->3)-GlcNAc](3) and [GlcA-(beta 1-->3)-GlcNAc](5) as the starting substrates agreed semi-quantitatively with experimental data using the same parameters. The mechanism of the hyaluronidase reaction is a combination of branched probabilistic cycles. The condensation reaction is much weaker than the transglycosylation reaction but contributes to product distribution at the final stage of the reaction, preventing complete hydrolysis of the substrates.
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PMID:Monte Carlo simulation of hyaluronidase reaction involving hydrolysis, transglycosylation and condensation. 1196 43


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