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:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fumaric acid (FA) suppressed the carcinogenesis in the liver of rats fed 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB), and a study was performed to examine the effect of FA on deoxyribonucleic acid (DNA) synthesis and subcellular structures of hepatocytes under the anticarcinogenic regimens. Male Donryu strain rats were given 3'-Me-DAB by being fed a diet containing 0.06% 3'-Me-DAB for 50 d. They were then given a diet containing 1% FA and drinking water containing 0.025% FA for 53 to 69 weeks. Hepatocytes were isolated from the liver by the collagenase perfusion method and placed in culture, and their activity for DNA synthesis was measured in terms of the incorporation of [3H]dThd into DNA. An enhanced DNA synthesis of hepatocytes was noted in the rats given FA, indicating that FA enhanced the proliferation of hepatocytes to counteract the carcinogenic effect of 3'-Me-DAB. An electron microscopic examination indicated that the distribution of subcellular organella was almost normal in the FA-treated hepatocytes.
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PMID:Inhibitory effect of fumaric acid on 3'-methyl-4-(dimethylamino)azobenzene-induced hepatocarcinogenesis in rats. 251 46

Recently, we have demonstrated that carbachol, a cholinergic agonist, stimulates the hydrolysis of phosphoinositides (PI) in the inner medullary (IM) slices from the rabbit kidney. In order to localize the effects of carbachol in the IM, we measured PI hydrolysis in IM collecting duct (CD) cells which form approximately 50% of the IM and play an important role in determining the final composition of the urine. The IMCD cells were prepared from IM slices of the rabbit kidney by treatment with collagenase followed by addition of water to lyse the cells other than IMCD cells. To measure PI hydrolysis, the IMCD cells were incubated with [3H]inositol for its incorporation into PI before measurement of inositol phosphates (IP) released and accumulated in the presence of LiCl which prevents the dephosphorylation of IP. Carbachol (1 mM) produced greater than 16-fold increase in the release of IP (from 1.53 +/- 1.34% in control to 26.26 +/- 4.59% in drug-treated) in the isolated IMCD cells. The effect was concentration-dependent with an EC50 (50% maximum effective concentration) of 4 microM carbachol. Carbachol-stimulated PI hydrolysis was blocked completely by 1 microM atropine, a muscarinic antagonist, and not by 1 microM hexamethonium, a nicotinic antagonist. The nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium iodide (1 mM), had no significant effect on PI hydrolysis in the IMCD cells. We conclude that the stimulation of PI hydrolysis by cholinergic agents in the IMCD cells occurs through their interaction with muscarinic receptors and this process may play a role in the diuretic and natriuretic effects of these agents.
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PMID:Cholinergic stimulation of phosphoinositide hydrolysis in renal medullary collecting duct cells. 253 9

Iotrolan, a nonionic, hexaiodinated dimer, is an extremely hydrophilic compound (P = 0.005). Due to its larger Stokes' radius compared with monomeric compounds such as metrizamide, the diffusion time through membranes is extended. Iotrolan deforms erythrocytes only minimally. There is practically no binding to plasma proteins. The new contrast agent has been shown to exert a very limited effect on the complement system (in vitro); it does not inhibit lysozyme (a standard enzyme) in concentrations less than 100 mg I/ml. To inhibit activity of the enzyme collagenase, much higher concentrations of iotrolan than of metrizamide or iopamidol are needed and this could offer an advantage when used for diskography preceding diskolysis with collagenase. After a single intravenous injection in rats, iotrolan has an LD50 of 28.3 g I/kg - the best general tolerance known for water-soluble contrast media thus far. The superior tolerance of iotrolan compared with iohexol and iopamidol (p less than or equal to 0.05) in rats is statistically significant. On the basis of preclinical experience, iotrolan is a very promising contrast medium for intrathecal and intravascular use.
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PMID:Physicochemical properties and general pharmacology of the nonionic dimer iotrolan. 256 4

To determine and compare the direct effects of prostaglandin F2a (PGF2a) and human chorionic gonadotropin (hCG) on luteal cell progesterone production in vitro, 9 human corpora lutea obtained at tubal ligation were minced and treated with collagenase to disaggregate luteal cells. Dispersed luteal cells (80% viable) were incubated in air at 37 degrees C in a shaking water bath for 3 h and total progesterone in the media and cells was determined by radioimmunoassay. Optimum progesterone production was obtained using 25,000 or more cells per incubate and an incubation time of 2-4 h. hCG-stimulated progesterone production increased significantly with 0.01 IU to as high as 100 IU. In the early luteal phase (days 1-5 post ovulation or days 15-20 of the luteal phase), PGF2a (10-1000 ng) significantly inhibited progesterone production but significantly stimulated progesterone production in the mid-luteal phase (days 21-25). PGF2a had no effect on luteal cell progesterone production in the late luteal phase (days 26-30). This age-dependent direct effect of PGF2a on human luteal cell progesterone production in vitro indicates a role for PGF2a in the total intragonadal regulation of progesterone output, possibly through a paracrine or autocrine manner directed towards synchronizing luteal progesterone secretion and endometrial preparation for nidation.
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PMID:Effect of human chorionic gonadotropin and prostaglandin F2a on progesterone production by human luteal cells. 260 39

1. Canine obstructive lymphoedema was created in one hind leg of 30 dogs by irradiation of the groin and surgical removal of surviving lymph glands and lymphatics. The opposite leg served as a control. Once the oedema had stabilized, groups of 10 dogs were treated orally with 12.5 mg day-1 kg-1 for 8 months with either one of the benzopyrones coumarin (2H-1-benzopyran-2-one) and 7-hydroxycoumarin (7-hydroxy-2H-1-benzopyran-2-one), or placebo. 2. The two benzopyrones significantly (P less than 0.01) but gradually reduced the oedema by 20-30% over 8 months, as judged by circumferential measurements of the oedematous and control limbs. There was no change with the placebo. 3. In the oedematous fluids (lymph and interstitial fluid), benzopyrone treatment reduced the protein content and increased acid and neutral proteinase activity compared with the control limbs, while the levels of the proteinase inhibitor alpha 2-macroglobulin remained unchanged. Furthermore, these active drugs reduced the excess water content, thickness and hydroxyproline content of skin biopsies from oedematous limbs compared with those from control limbs. No changes were observed for the placebo group. 4. These biochemical changes suggest that benzopyrones can reduce the excess proteinaceous fluid in lymphoedema by increasing the levels of proteinase activity relative to the number of proteinase inhibitors. As a secondary event the amount of fibrosis in the skin is also reduced, presumably by an increase in collagenase activity from the mononuclear phagocytes. 5. These results support the hypothesis that benzopyrones activate the production of proteinases by mononuclear phagocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coumarin and 7-hydroxycoumarin treatment of canine obstructive lymphoedema. 266 58

Amiprilose HC1 (SM-1213), a nontoxic modified hexose sugar, was evaluated in in vivo and in vitro models of synovitis. In 8 sequential trials, 90 Louvain (LOU) rats and 91 Sprague-Dawley (SD) rats were immunized with chick type II collagen and given amiprilose HC1 in water (1 mg/ml) or water alone. In the LOU rats, the arthritis incidence was 7/46 (15%) in the amiprilose HC1 group vs 16/44 (36%) in the water group (p less than 0.01). In the SD rats, the incidence was 28/46 (60%) in the experimental vs 33/45 (73%) in the control group (p greater than NS), although the prevalence of arthritis on Days 16 and 21 was significantly (p less than 0.03) lower in the experimental group. Amiprilose HC1 did not affect the antibody titers or delayed-type hypersensitivity to collagen, or T cell subset distribution in the LOU experiments. Two analogues, SM-1211 and SM-1212, did not alter this disease. No toxicity was noted. At a nontoxic concentration of 1 mg/ml, amiprilose HC1 suppressed 3H thymidine incorporation in cultured rabbit synovial fibroblasts by 78% and resulted in the appearance of numerous intracytoplasmic granules/vacuoles. These effects were partially antagonized by indomethacin or dexamethasone at 10(-7) M. SM-1211 was inert in this system. Amiprilose HC1 system also reduced rabbit synoviocyte supernatant prostaglandin E2 levels up to 73% in a dose related fashion, but did not affect collagenase activity. These morphologic changes in synoviocytes, combined with anti-inflammatory and antiproliferative effects, provide evidence that amiprilose HC1 possesses modest and nontoxic antirheumatic properties. A search for analogues of this sugar with more substantial clinical activities is warranted.
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PMID:Evaluation of a modified hexose sugar, amiprilose hydrochloride, in experimental models of synovitis. 278

The process of uptake of endotoxin by cells of the reticuloendothelial system is of current interest. Rabbit peritoneal macrophages have been used to study macrophage-endotoxin interactions and have suggested a receptor-mediated process. It is generally believed that the site of in vivo endotoxin clearance is the liver and that this clearance involves the Kupffer cell population. In the current report, the uptake characteristics of iodine-125-labeled Salmonella minnesota lipopolysaccharide (LPS) were compared in both isolated rat Kupffer cells and elicited rat peritoneal cells. Both types of cells were isolated from male Sprague-Dawley rats fed a semisynthetic AIN-76 5% saturated-fat diet either by peritoneal lavage for peritoneal cells or by collagenase perfusion followed by purification on a 17.5% metrizamide gradient for Kupffer cells. Hot phenol water-extracted S. minnesota LPS was labeled with iodine by the chloramine-T method following a reaction with methyl-p-hydroxybenzimidate. The in vitro uptake of [125I]LPS by Kupffer cells was unsaturable up to concentrations of 33.33 micrograms/ml, while peritoneal cells became saturated at between 16.67 and 25 micrograms of LPS per ml. Uptake by both types of cells could be inhibited by a 10-fold excess of unlabeled LPS. Kinetic experiments demonstrated that Kupffer cells were unsaturable after 60 min of incubation, while peritoneal cells were saturable after 40 min of incubation. Pretreatment with 75 mM colchicine inhibited uptake by peritoneal cells but not Kupffer cells, while pretreatment with 12 mM 2-deoxyglucose inhibited uptake by Kupffer cells but not peritoneal cells. These results are consistent with a process of receptor-mediated endocytosis for peritoneal cells, while Kupffer cells may internalize endotoxins by absorptive pinocytosis. These results suggest that studies of peritoneal cell-endotoxin interactions do not accurately describe the physiologic process within the liver, the major site for the clearance of gut-derived endotoxins.
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PMID:Comparative studies of endotoxin uptake by isolated rat Kupffer and peritoneal cells. 282 79

Collagenase activity was considered to play an important role in the process of ulcer formation, as one of the aggressive factors. We measured the collagen metabolism using the restraint and water immersion stress ulcer model with time and studied the effects of cimetidine and misoprostol (PGE1 derivative) on the collagen metabolism. The active forms and total collagenases in the gastric mucosal connective tissues were elevated as early as at two hours after loading by restraint and water immersion stress, and a decrease in the amount of collagen (as hydroxyproline) was observed. Increase in the collagenase activity was inhibited in groups to which cimetidine or misoprostol was given before restraint and water immersion. From these results it is believed that an elevation of collagenase activity related directly to tissue destruction might be involved, as well as a decrease in the gastric mucosal blood flow, in the etiology of ulcers due to restraint and water immersion stress.
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PMID:Collagen and collagenase in ulcer tissue--2. Restraint and water immersion induced gastric lesions and effects of cimetidine and misoprostol. 284 Jul 58

Many of the common substrate digestion assays have the disadvantage of being tedious and expensive, thus aggravating serial determinations of collagenase activity. In the assay presented here, the proteolytic reaction proceeds on a sheet of chromatographic paper bearing spots of dried gelatin or collagen solutions. After application of the enzyme sample, the sheets are incubated in a water-saturated atmosphere for 45 min and the reaction products are visualized by spraying with chromatographic, ninhydrin-containing peptide reagents. By its specific yellow staining, the activity of bacterial collagenase can be discriminated from the gray, brown, red, or violet spots which are produced by eight tested noncollagenolytic proteases. The detection limit for collagenase activity reaches down to 0.002 U in a sample volume of 1-2 microliters dropped onto a spot of 25 microliters gelatin solution (3%), thus corresponding with the sensitivity of a conventional radioassay. The sensitivity for noncollagenolytic proteases is better than 2 ng per sample, herewith exceeding a common casein-agar diffusion test. The method is also evaluated for native collagen. Within 1.5 h, 100 samples can be assayed. An example for the application in a collagenase purification step (ion exchange chromatography) is also presented.
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PMID:A rapid and sensitive microassay for bacterial collagenase and other proteolytic activities on collagenous substrates. 284 9

Human skin collagenase activity was examined against type III collagens, in both soluble and fibrillar form, from different animal species. In either form, human, dog, and cat type III were degraded 10- to 30-fold faster than was that from guinea pig and nearly 100-fold more readily than chick type III. These differences in susceptibility were mirrored by essentially identical differences in the rate of trypsin cleavage of the same substrates. Human, dog, and cat type III were cleaved most rapidly by trypsin, guinea pig III more slowly, and chick III was completely resistant to the serine protease. Arrhenius plots, relating enzyme activity to temperature, revealed differences in the various type III substrates consistent with their collagenase and trypsin susceptibilities. Human, dog, and cat type III collagens yielded nonlinear plots, with accompanying activation energies which decreased at temperatures above 26 degrees C; guinea pig type III displayed a plot which deviated only slightly from linearity while the plot for chick type III was completely linear. These data strongly suggest that type III collagens display substantial variability in the stability of the helix at or near the collagenase cleavage site. The susceptibility of these type III substrates as reconstituted fibrils was also examined. The relative rates of degradation of these substrates by collagenase, and by trypsin, were the same as those observed in solution. The absolute rates of degradation of collagen in fibrillar form, however, were massively lower than predicted by extrapolation from solution values. This reduction in rate is even greater for type III than for type I collagens. Thus, whereas in solution type III substrates are cleaved much faster than type I collagens, in fibrillar form these differences are less than 2-fold. These data, together with values for activation energies and deuterium isotope effects on type III fibrillar substrates, reinforce the concept that helical integrity near the collagenase cleavage site is a major specifier of the rate of collagenase activity. Furthermore, the data suggest that the exclusion of water accompanying the tight packing of monomers into fibrils presents a major energy barrier to collagenase activity, which is particularly large for type III collagen.
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PMID:Degradation of monomeric and fibrillar type III collagens by human skin collagenase. Kinetic constants using different animal substrates. 298 30


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