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)

The effects of metabolic and respiratory acidosis and alkalosis on cellular calcium metabolism were studied in rat kidney cells dispersed with collagenase. In both types of acidosis, the intracellular pH, total cell calcium, and the cell relative radioactivity after 60 min of labeling are significantly depressed. Kinetic analysis of 45-ca desaturation curves shows that acidosis decreases all three cellular calcium pools and depresses calcium fluxes between the superficial and cytosolic pools and between the cytosolic and mitochondrial pools. In alkalosis the intracellular pH, the total cell calcium, and the cell relative radioactivity are significantly increased. Kinetic studies show that in alkalosis, only the mitochondrial pool is consistently increased. Calcium exchange between the mitochondrial and cytosolic pool is increased in metabolic alkalosis only. These results suggest that hydrogen ion is an important modulator of calcium metabolism, and that the intracellular pH rather than extracellular pH is the critical factor in determining the calcium status of cells during altered acid-base conditions.
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PMID:Effect of pH on the calcium metabolism of isolated rat kidney cells. 4 33

The paper represents a summary of our studies in which in vitro perfusion of human and animal coronary vessels was carried out. Formation and uptake of lipids in perfused human coronary arteries were studied under a vairety of experimental conditions, including exposure to carbon monoxide. The effect of collagenase on lipid synthesis and transport in carotid arteries of dogs was also studied. Human plasma with hydrogen-3-labeled cholesterol and carbon-14-acetate was used to perfuse human blood vessels. Autologous plasma was employed. Inhibition of cholesterol uptake was accomplished by the addition of 7-ketocholesterol (concentrations of 0.005 to 1 mum/ml) to the perfusate. Both atherosclerotic and normal human coronary arteries incorporated 14C-acetate into lipids but failed to synthesize either cholesterol of cholesterol esters. Similar results were obtained in human saphenous veins perfused at arterial pressure. Cholesterol uptake from the perfusion fluid was demonstrated in atherosclerotic and normal human coronary arteries as well as in human saphenous veins. Carbon monoxide increased permeability of the arterial wall to cholesterol uptake. In dog arteries exposed to collagenase marked increases in cholesterol uptake were found, but total lipid synthesis was reduced; the relative synthesis individual lipids remained unchanged. The addition of 7-ketocholesterol to the perfusate reduced cholesterol uptake by the vessel by 90 percent. Inhibition of cholesterol uptake was present in all species and was not due to oxidation of cholesterol to 7-detocholesterol in the perfusate. The results illustrate that human coronary arteries as well as human saphenous veins synthesize lipids but not cholesterol. Cholesterol flux into the artery is augmented by carbon monoxide and collagenase. The data also show that active inhibition of cholesterol uptake in the arterial wall can be accomplished by competitive inhibition with 7-ketocholesterol.
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PMID:Lipid metabolism in perfused human and dog coronary arteries. 16 13

Solubilization of the normal glomerular basement membrane with various solvents revealed that the material is held together by hydrogen and disulfide linkages as well as ionic salt bridges which ionize at around pH 10.0. Pronase digestion indicated that differences in susceptibility to enzyme digestion exist between normal and nephritic membrane. Titration of a urea-insoluble material indicated that some alteration must have taken place in the association between various components of the nephritic basement membrane. Chemical analysis of alkali-solubilized fractions suggested that greater alkali susceptibility of the nephritic material may be present. A collagen-like material resembling both tendon and dog basement membrane collagen in its amino acid composition was isolated. It contained 10% hexose, but in addition to glucose and galactose, mannose was also detected. A glycopeptide fraction obtained by pronase and collagenase digestion has a carbohydrate composition similar to the collagen-like material above. These substances probably represent incompletely digested fragments of the basement membrane.
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PMID:Studies of normal and nephritic rat glomerular basement membrane. 23 74

Testes of 29-35-day-old rats were separated into seminiferous tubules and interstitial tissue by collagenase treatment and examined by incubation studies with radioactive substrates. The activity of testosterone 5alpha-reductase/g protein in the interstitial tissue was 37 times greater than that in the tubules. The site of formation of 5alpha-reduced C21- and C19-steroids from progesterone was found to be primarily in the interstitial tissue. In the interstitial tissue, testosterone 5alpha-reductase activity, which was stimulated 300-fold by the addition of NADPH, was localized in the microsomal fraction (8,000-105,000 X g precipitate). NADPH was five times as effective a hydrogen donor as NADH when the washed microsomal fraction was the source of the enzyme. The formation of 5alpha-reduced C21- and C19-steroids from pregnenolone and progesterone was demonstrated in the microsomal fraction of interstitial tissue. These results indicate that in 29-35-day-old rat testes, 5alpha-reduction of C19-delta4-3-ketosteroids and the formation of 5alpha-reduced C21- and C19-steroids from pregnenolone take place largely in the microsomes of interstitial tissue.
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PMID:Localization of delta4-5alpha-reductase in immature rat testes. 74

The interstitium is the final link in the transportation of nutrients from the bloodstream to the individual cells of an organism. To assess interstitial fluid transport in normal and inflamed tissue, the hydration (H, ml H2O/g dry wt) and hydraulic conductivity (Kp, 10(-8) cm2.s-1.cmH2O-1) of bovine pericardial stroma were determined. The effect of enzymes and neutrophil-derived products of inflammation on the properties of the interstitial model were determined. Samples of the pericardium were exposed separately to trypsin, elastase, hyaluronidase, collagenase, superoxide radicals, and hydrogen peroxide. After exposure, the tissues were washed repeatedly in physiological saline and equilibrated in transport chambers heated to 37 degrees C and pressurized to 50 cmH2O. Fluid flow across the tissues was monitored. A section of tissue was removed and weighed. The tissue section was subsequently dried and reweighed. Tissue thickness, H, and Kp were calculated. H and Kp of the control tissues were 2.82 +/- 0.04 and 1.71 +/- 0.07, respectively. Hydration was significantly increased (22-38%) by exposure to trypsin, elastase, collagenase, and superoxide radicals. Kp increased significantly (30-1055%) in the groups treated with trypsin, hyaluronidase, collagenase, and superoxide radicals. The inflammatory mediators generally increased the hydration and/or the hydraulic conductivity of the model. These results indicate that neutrophil-derived products could be involved in the development of interstitial edema during the inflammatory process.
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PMID:Oxygen radicals, enzymes, and fluid transport through pericardial interstitium. 131 Feb 33

There are two types of collagenases, products of two distinct genes, called MMP-1 (matrix metalloproteinase 1 or "fibroblast-type collagenase") and MMP-8 ("neutrophil collagenase"). In synovial fluid, MMP-8 is stored as latent proenzyme in polymorphonuclear neutrophils. MMP-8 is activated by hypochlorous acid produced by myeloperoxidase from hydrogen peroxide and chloride ion and by the hydroxyl radical produced in Haber Weiss reaction fed by superoxide produced by, eg, NADPH (reduced nicotinamide adenine dinucleotide) oxidase and xanthine oxidase. In addition to activation upon secretion, oxidatively modified MMP-8 is susceptible to a subsequent proteolytic attack and activation by cathepsin G. The authors suggest that activation of neutrophil-derived MMP-8 involves oxidative, nonproteolytic activation upon secretion and a more slowly progressive proteolytic activation by cathepsin G (or chymases and tryptases), and that these oxidative and proteolytic activation mechanisms act in concert. In contrast to MMP-8, MMP-1 is synthesized de novo and secreted immediately after synthesis by fibroblasts, macrophages, and some epithelial cells. Human rheumatoid synovial tissue contains mainly fibroblast-type MMP-1 collagenase as assessed by collagenase extracted from synovial tissue and by MMP-1 and MMP-8 immunostaining. It is suggested that in vivo, MMP-1 in synovitis tissue is activated by a plasminogen activator/plasminogen/prostromelysin (alternatively tryptases)/proMMP-1 cascade. In conclusion, MMP-8 and MMP-1 show type-specific compartmentalization and modes of activation in rheumatoid synovial fluid and tissue.
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PMID:Collagenase in synovitis of rheumatoid arthritis. 141 81

The effects of various reactive oxygen species on latent human neutrophil and fibroblast-type interstitial collagenases were studied. Latent human neutrophil collagenases (proMMP-8) was efficiently activated by hypochlorous acid and hydrogen peroxide and less efficiently by the serine proteinases trypsin and chymotrypsin. Human plasmin and plasma kallikrein did not activate latent human neutrophil collagenase. The activation of latent human neutrophil collagenase by hypochlorous acid and hydrogen peroxide corresponded to the activation obtained with the other known non-proteolytic activators phenylmercuric chloride and gold thioglucose. The activation by hydrogen peroxide was inhibited by mannitol and desferoxamine, suggesting a localized Fenton-type reaction to be responsible for the generation of hydroxyl radical and/or hydroxyl radical-like reactive oxygen pathway of neutrophil procollagenase does not involve plasmin and plasma kallikrein, which are efficient proteolytic activators of latent fibroblast-type procollagenase (proMMP-1). Fibroblast procollagenase was also slightly activated by hypochlorous acid and gold thioglucose. Thus neutrophil procollagenase seems to prefer non-proteolytic means of activation and reactive oxygen species can be regarded as potent activators in vivo. Synovial-fluid neutrophils from rheumatoid arthritis patients were found to release collagenase in 30% active form when compared to same patients' peripheral blood neutrophils, which released collagenase in completely latent form. This may indicate that the triggering of neutrophil at the site of inflammation in vivo involves initial oxidative activation of collagenase upon the degranulation process.
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PMID:Reactive oxygen species as regulators of human neutrophil and fibroblast interstitial collagenases. 144 75

The levels of volatile sulphur compounds (VSC) in periodontal pockets and mouth air have been found to correlate with severity of the disease process. The purpose of this study was to examine the influence of hydrogen sulphide and methyl mercaptan on protein metabolism of human gingival fibroblasts. The incorporation of labelled amino acids into protein was used to evaluate effects on total protein content. Changes in collagenous protein concentration were monitored by release of radioactivity following collagenase digestion as well as direct analysis of hydroxyproline. Both thiols were found to reduce total protein synthesis, with mercaptan exerting a greater adverse effect. In cultures exposed to mercaptan, total protein was reduced by 35%. The changes in total protein were accompanied by a corresponding decrease in collagenase-digestible protein. Hydroxyproline analysis of CH3SH-exposed cultures confirmed the changes associated with collagenous proteins. It indicated that in comparison to the controls the CH3SH-exposed cultures had a 70% reduction in collagen which resulted from a combined effect of suppressed synthesis and increased rate of collagen degradation. The possibility of thiol reaction with collagen was determined using in vitro systems in which type I collagen was reacted with varying concentrations of [35S]-H2S. The carboxymethyl (CM) cellulose assays of resulting reaction mixtures indicate that [35S]-radioactivity was incorporated directly into alpha 1, alpha 2, beta 11, beta 12 peptide chains. Furthermore, upon exposure of collagen to elevated H2S concentrations, the H2S converted some of the acid-soluble collagen to a more soluble product which could be extracted in neutral salt and analyzed by CM-cellulose chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of volatile thiol compounds on protein metabolism by human gingival fibroblasts. 146 May 44

Cationic glucose oxidase, prepared by amidation of its free carboxylic groups, has prolonged retention in tissues, resulting in sustained release of hydrogen peroxide generated during oxidation of endogenous glucose. Increased levels of hydrogen peroxide can inhibit superoxide dismutase activity, thereby promoting reduction of transition metal ions, particularly iron and copper, by superoxide anions. Therefore, hydrogen peroxide can generate highly reactive hydroxyl radicals through a superoxide-driven Fenton reaction. Amidated glucose oxidase injected into rabbit cornea produces corneal opacification within 3-4 days and severe corneal damage by 7 days. Ultrastructural studies revealed typical tissue lesions observed in corneal melting. Heat-inactivated amidated glucose oxidase had no effect during the first 3-4 days. However, a gradual opacification occurred thereafter, resulting in some cases, in a severe opacity by 7 days. These results are consistent with an oxidative attack on corneal glycoconjugates by radicals derived from glucose oxidase-generated hydrogen peroxide during the first 3-4 days. Invading phagocytic cells are responsible for lesions observed with the inactive enzyme and for the progression of the initial lesions caused by the active enzyme. Stimulated phagocytic cells not only produce active oxygen species during the respiratory burst, but also release neutral collagenase and acid lysosomal hydrolases that contribute to and amplify the degradation of the extracellular matrix.
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PMID:Role of active oxygen species in corneal ulceration. Effect of hydrogen peroxide generated in situ. 215 13

Several phosphonamide peptides having the general structure R-PO(OH)-Xaa-Yaa-Zaa were synthesized and tested for inhibition of Clostridium histolyticum collagenase. Inhibition was found to depend on the nature of R, Xaa, Yaa and Zaa such that the maximal affinity (Ki = 5 nM) was observed when R = p-nitrophenylethyl, Xaa = Gly, Yaa = Pro and Zaa = 2-aminohexanoic acid; this represents the tightest binding of inhibitor reported to date for any bacterial collagenase. Substitution of the p-nitrophenylethyl by a methyl group led to a 500-fold decrease of the potency, highlighting the existence of optimal interaction between the nitrophenylethyl side chain and one subsite of the enzyme. Replacement of the NH group in glycine residue (Xaa position) by -O- or -N-CH3 produces significantly less potent inhibitors, presumably due in part to the loss of a hydrogen bond between the inhibitor and collagenase active site. These phosphonamidates are thought to be acting as transition-state analogues of the peptide substrate.
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PMID:Inhibition of Clostridium histolyticum collagenases by phosphonamide peptide inhibitors. 216 50


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