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 influence of plasma fibronectin on the cleavage of interstitial collagen types I, II, and III by mammalian collagenase was investigated. To this end, rheumatoid arthritis synovial tissue collagenase was isolated from tissue culture supernatants. A highly active enzyme preparation was obtained. Different dilutions of the collagenase were incubated in tubes coated with [3H]-labeled collagens. Liberation of labeled fragments in the presence (200 micrograms per ml) or absence of fibronectin was measured at different time intervals (1-30 min). A significant inhibition of collagen degradation was observed in case of type I and type III collagens. Analogous experiments were carried out using collagen-coated tubes preincubated with fibronectin at a concentration of 200 micrograms/ml. Here, a strong inhibition (76 percent) of type III collagen digestion by collagenase was observed, while the cleavage of type I or type II collagen was completely unchanged after preincubation with fibronectin. A direct attack of the collagenase preparation on plasma fibronectin could be excluded in control digestion experiments using radioiodinated fibronectin as substrate.
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PMID:Influence of plasma fibronectin on collagen cleavage by collagenase. 630 85

A collagenase previously reported to accumulate in the medium of cultures of BALB/c 3T3 cells on infection with Mycoplasma orale [Kluve, Merrick, Stanbridge & Gershman (1981) Nature (London) 292, 855-857] was partially purified and characterized. With regard to purification properties, activation, sensitivity to inhibitors and relative molecular mass the enzyme was similar to previously reported vertebrate collagenases, but could not be unequivocally distinguished from bacterial collagenases. With regard to substrate-specificity and reaction products, however, the collagenase was typical of vertebrate collagenases and distinct from bacterial collagenases. Specifically, the enzyme displayed a preference for type III collagen and type I collagen, a somewhat decreased ability to degrade type II collagen, and a very limited ability to degrade type IV collagen. The initial products of the action of the collagenase on type I collagen were characterized as fragments one-quarter and three-quarters of the length of the intact collagen molecule. Because the properties of the collagenase produced by cultures of mycoplasma-infected BALB/c 3T3 cells are those of a mammalian-type (vertebrate-type) enzyme, we have concluded that the collagenase is a product of the mouse (BALB/c 3T3) genome, and is not produced by the mycoplasma. Therefore it appears that infection of BALB/c 3T3 mouse fibroblasts with Mycoplasma orale induces the mouse cells to produce and secrete collagenase.
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PMID:Mycoplasma-induced BALB/c 3T3 collagenase is a mammalian enzyme. 630 50

A previous report that the 3 alpha collagen chain of hyaline cartilage was cleaved by human collagenase could not be confirmed when the 1 alpha 2 alpha 3 alpha collagen fraction was freed of all contaminating type II collagen. All three minor collagen chains, 1 alpha, 2 alpha and 3 alpha, were totally resistant to highly purified collagenases from both rheumatoid synovial and gastric mucosal tissues. This finding and CNBr-peptide patterns suggest that, despite the close homology with alpha 1 (II), the 3 alpha chain is a unique collagen component, possibly combined with 1 alpha and 2 alpha in heterotrimeric molecules. In contrast, a 3 alpha-like component from fibrocartilage was cleaved by collagenase and gave a CNBr-peptide pattern more typical of alpha 1 (II) than of the collagenase-resistant 3 alpha of hyaline cartilage.
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PMID:All three chains of 1 alpha 2 alpha 3 alpha collagen from hyaline cartilage resist human collagenase. 632 61

Pig articular cartilage, overlaid with a minced preparation of synovium from the same joint, underwent extensive matrix degradation during a two-week culture period. This degradation was associated with de novo synthesis by the synovium of specific neutral proteoglycan- and collagen-degrading enzymes. Both enzymes exhibited neutral pH optima, and were inhibited by serum and the metal ion chelators EGTA and 1,10-phenanthroline. The neutral proteoglycanase cleaved the core protein of isolated proteoglycan. The effects of some anti-inflammatory drugs on synovial enzyme production and cartilage metabolism were investigated. The steroids, dexamethasone and prednisolone, inhibited production of both enzymes whereas the non-steroidal anti-inflammatory drugs (NSAID's), flurbiprofen and indomethacin, slightly increased medium enzyme levels. Flurbiprofen and indomethacin had no effect on the extent of synovium-mediated cartilage degradation as assessed histologically. Inhibition by the steroids of synovial collagenase production correlated with inhibition of cartilage collagen breakdown, whereas inhibition of synovial proteoglycanase production did not prevent extensive proteoglycan breakdown. Experiments using radiotracer techniques indicated that dexamethasone, whilst partially inhibiting synovium-mediated proteoglycan degradation, severely inhibited cartilage proteoglycan synthesis thus resulting in net proteoglycan loss.
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PMID:Studies on the release of proteolytic enzymes during synovium-induced cartilage breakdown in vitro and the actions of anti-inflammatory drugs. 632 20

Nonenzymatic glucosylation of type I and type II collagens was examined by incubating collagen substrates with D-glucose in vitro. In one set of experiments, unlabeled collagen was incubated with [14C]-glucose and the incorporation of [14C]-radioactivity into protein was determined by TCA precipitation. The incorporation was dependent on the concentration of glucose and the time of incubation. The glucosylated product was also examined by SDS-polyacrylamide slab gel electrophoresis. The results indicated that both alpha 1(I)- and alpha 2(I)-chains of type I collagen were glucosylated and the glucosylation occurred both with native and denatured collagen as substrate. In further studies [3H]-lysine-labeled collagens were glucosylated, the products reduced by NaBH4, and the [3H]-lysine-derived residues were separated by amino acid analyzer. After a 144 h incubation in vitro, 18.9% of [3H]-lysyl residues and 36.5% of [3H]-hydroxylysyl residues in type I collagen were substituted with glucose. In contrast, 47.9% of [3H]-lysyl residues and 68.1% of [3H]-hydroxylysyl residues in type II collagen were glucosylated after 144 h incubation. Based on quantitative amino acid analyses of the substrates, these values represent 27.6 lysine plus hydroxylysine residues substituted per triple-helical type I collagen molecule and 65.3 residues per triple-helical type II collagen molecule. Thus, type I and type II collagens display differential susceptibilities to nonenzymatic glucosylation. Finally, [3H]-proline-labeled type I collagen was glucosylated to varying extents, and the glucosylated products were used as substrates for human polymorphonuclear leukocyte collagenase. No difference in susceptibility to this collagenase was noted, irrespective of the extent of glucosylation.
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PMID:Nonenzymatic glucosylation of lysyl and hydroxylysyl residues in type I and type II collagens. 644 73

Chondrocytes produce large pericellular coats in vitro that can be visualized by the exclusion of particles, e.g., fixed erythrocytes, and that are removed by treatment with Streptomyces hyaluronidase, which is specific for hyaluronate. In this study, we examined the kinetics of formation of these coats and the relationship of hyaluronate and proteoglycan to coat structure. Chondrocytes were isolated from chick tibia cartilage by collagenase-trypsin digestion and were characterized by their morphology and by their synthesis of both type II collagen and high molecular weight proteoglycans. The degree of spreading of the chondrocytes and the size of the coats were quantitated at various times subsequent to seeding by tracing phase-contrast photomicrographs of the cultures. After seeding, the chondrocytes attached themselves to the tissue culture dish and exhibited coats within 4 h. The coats reached a maximum size after 3-4 d and subsequently decreased over the next 2-3 d. Subcultured chondrocytes produced a large coat only if passaged before 4 d. Both primary and first passage cells, with or without coats, produced type II collagen but not type I collagen as determined by enzyme-linked immunosorbent assay. Treatment with Streptomyces hyaluronidase (1.0 mU/ml, 15 min), which completely removed the coat, released 58% of the chondroitin sulfate but only 9% of the proteins associated with the cell surface. The proteins released by hyaluronidase were not digestible by bacterial collagenase. Monensin and cycloheximide (0.01-10 microM, 48 h) caused a dose-dependent decrease in coat size that was linearly correlated to synthesis of cell surface hyaluronate (r = 0.98) but not chondroitin sulfate (r = 0.2). We conclude that the coat surrounding chondrocytes is dependent on hyaluronate for its structure and that hyaluronate retains a large proportion of the proteoglycan in the coat.
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PMID:Pericellular coat of chick embryo chondrocytes: structural role of hyaluronate. 650 14

Certain physical properties of two molecular forms of short-chain (SC) cartilage collagen [Schmid, T. M., & Linsenmayer, T. F. (1983) J. Biol. Chem. 258, 9504-9509] have been determined. The 59K form has both a collagenous and a noncollagenous domain, and the 45K form has only the collagenous one. By circular dichroic spectropolarimetry, both forms show the characteristic spectrum of a collagen triple helix with a maximum ellipticity at 222 nm and a minimum at 197 nm. The denaturation temperature (Tm) of the helical structure of both forms, as monitored at 222 nm, is approximately 47 degrees C. Thus, the presence of the nonhelical domain does not greatly affect this property. After thermal denaturation, however, the renaturation of the 59K form is much more rapid than that of the 45K form, regaining greater than 60% of its helical structure within 40 min. The 45K form regains at most 15%, even after 24 h. Gel filtration on Sephacryl S-500, run under nondenaturation conditions, showed that the molecules renatured from the 59K form had regained a structure indistinguishable from native ones, while the 45K had not. The noncollagenous domain of the 59K form could be obtained by digestion with bacterial collagenase. This domain, as previously reported, contains no disulfide bonds. But, it is very stable, requiring both detergent and heating to separate its component chains. We hypothesize that the chains within this domain are tightly held together by strong, noncovalent forces, such as hydrophobic bonds, which are refractory to thermal denaturation. These maintain the chains in proper registry, thus facilitating rapid renaturation of the helical domain.
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PMID:Denaturation-renaturation properties of two molecular forms of short-chain cartilage collagen. 670 82

Recent reports on the Pond-Nuki model of osteoarthritis in the dog have provided evidence for partial disruption of the collagen network. The possibility of collagenase involvement in these localized changes was studied. Animals were killed 2, 4, 8, and 12 weeks after surgery. The left knee served as a sham-operated control. Cartilages from femoral condyles were processed for light and electron microscopy and assayed for collagenolytic activity by a direct tissue assay, based on the measurement of digestion of endogenous cartilage collagen. Animals killed at 2 and 4 weeks showed fibrillation and mild erosion of femoral condyles, which usually progressed to ulceration by 8 and 12 weeks. Electron microscopy demonstrated fiber disruption of the mid-zone perilacunar collagen as early as 2 weeks after the operation. Total collagenolytic activity, measured after activation by aminophenylmercuric acetate, was significantly higher in decreased cartilage than in controls of 2, 4, and 8 weeks; the peak value was at 4 weeks. Collagenase was shown, by its specific action on type I collagen, to be present at 2 and 4 weeks; however, other metalloproteases may also contribute to the digestion. The correlation between increased collagenolytic activity and the early osteoarthritic changes in cartilage suggests a role of this enzyme activity in the disease process.
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PMID:Collagenolytic activity and collagen matrix breakdown of the articular cartilage in the Pond-Nuki dog model of osteoarthritis. 687 Sep 69

Traumatised normal pig synovium has been cultured with normal pig articular cartilage for 14 days. The breakdown of cartilage collagen and proteoglycan during culture was accompanied by the appearance in the culture medium of collagenase and proteoglycanase respectively which appeared to be derived from the synovium. There was good correlation between culture medium levels of collagenase and cartilage collagen breakdown, but the relationship between synovial proteoglycanase and cartilage proteoglycan breakdown was not so clear-cut. Corticosteroids consistently inhibited breakdown of cartilage collagen but not proteoglycan, and inhibited the production of the proteolytic enzymes. High concentrations of aurothiomalate (10(-3)M) inhibited collagen breakdown and partially reduced culture medium enzyme levels. Non-steroidal antiinflammatory agents such as flurbiprofen and indomethacin had no effect on the breakdown of collagen or proteoglycan and tended to increase culture medium enzyme levels. This culture system may be used to provide further information concerning the action of antirheumatic drugs.
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PMID:Biochemical and pharmacological studies on synovium-cartilage interactions in organ culture. 704 93

We evaluated the effect of administering orally two synthetic analogues of retinoic acid, 13-cis-retinoic acid and all-trans-N-(4-hydroxyphenyl)-retinamide to age-matched female Sprague-Dawley rats immunized with native chick type II collagen in incomplete Freund's adjuvant. Ingestion of a diet containing 13-cis-retinoic acid was associated with a significant increase in the severity of collagen arthritis, but there was no effect on weight gain or hemagglutinating antibody titers and delayed-type hypersensitivity to type II collagen. In two separate trials, ingestion of 4-hydroxyphenyl retinamide also significantly enhanced the severity of arthritis. Monolayer cultures of dissociated synovial cells taken from arthritic rats, but not nonarthritic rats, released prostaglandin E2 (PGE2) and collagenase into the medium. The level of PGE2 production was significantly decreased by in vivo or in vitro exposure to 4-hydroxyphenyl retinamide, whereas the addition of 13-cis-retinoic acid to the cultures had no effect on PGE2 release by the arthritic synovial cells. Five rats fed the 13-cis-retinoic acid-containing diet for 5 mo did not develop clinical or histologic evidence of arthritis. These data demonstrate that both retinoids possess potent enhancing properties for an experimentally inducible autoimmune arthritis, that synovial cells produce PGE2 and collagenase in this model, and that production of PGE2 can be suppressed by 4-hydroxyphenyl retinamide.
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PMID:Augmentation of collagen arthritis by synthetic analogues of retinoic acid. 714 2


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