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 collagen content of the media of infrarenal aorta has been compared in age- and sex-matched normal aorta and dilated and nondilated atherosclerotic aorta. The proportion of collagen was increased in aneurysmal aorta from 62% to 84% and appears to be the result of preferential elastin degradation. The ratio of type I to type III collagen, estimated from sodium dodecyl sulfate-polyacrylamide gel electrophoresis of specific cyanogenbromide peptides, did not vary significantly from 2:1 in any of the three groups of aortas. There was no evidence of increased collagenase activity in unruptured aneurysmal aorta. Collagenase activity was increased in ruptured aneurysmal aorta but could only be satisfactorily measured after resolution from the endogenous tissue inhibitor of metalloproteinases. We suggest that only limited collagen turnover occurs in the media of abdominal aortic aneurysms before rupture. A subgroup of three patients with a significant family history of aneurysm had lower amounts of type III collagen in the aortic media, suggesting that abnormalities in type III collagen may be one of the genetic factors contributing to familial clustering of aneurysms.
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PMID:Collagen in abdominal aortic aneurysm: typing, content, and degradation. 282 27

Thirteen cases of elastofibroma have been studied by conventional light and electron microscopy, as well as by histochemistry and immunohistochemistry. By light microscopy elastinophilic material appeared as huge fibers crossing collagen bundles. Immunohistochemistry demonstrated a strong positivity for elastin in numerous and circumscribed areas of the extracellular matrix. By electron microscopy, collagen consisted of 40-50-nm wide fibrils, and elastin was made of large aggregates of moderately electron-dense material surrounding a very thin, apparently normal, elastin core. At high magnification these aggregates consisted of short tubules, often in regular arrays, surrounded by microfibrils and microfilaments. These data, associated with selective digestions on thin sections with elastase, purified collagenase, hyaluronidase, and chondroitinase ABC, revealed that elastic fibers in elastofibroma seem to be made of true elastin surrounded by an enormous amount of hydrophilic material, in which some elastin, chondroitin sulfates, and collagenase type-VII sensitive material are aggregated forming a rather ordered array of short tubules.
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PMID:Elastofibroma: an in vivo model of abnormal neoelastogenesis. 284 Jul 67

Studies were undertaken to evaluate factors capable of influencing the intensity of contact hypersensitivity (CH) and delayed-type hypersensitivity (DTH) responses in mice. It is well known that the exposure of animals to ultraviolet radiation (UVR) causes a depression of CH and DTH responses whereas the injection of mice with nanogram quantities of pertussis toxin (PT) before sensitization results in greatly augmented CH responses following hapten challenge. Histopathology and biochemical quantitation of myeloperoxidase (MPO) activity in biopsies obtained from the challenged ears from normal, UVR-exposed, or PT-treated animals determined that a direct correlation existed between the intensity of the ear-swelling response and the degree of neutrophil infiltrate into the challenge site. Few neutrophils were observed to infiltrate into the ears of UVR-exposed animals when compared to normal animals, whereas a pronounced neutrophil infiltration was observed in the challenged ears of PT-pretreated animals. These observations led us to question whether tissue-infiltrating neutrophils, or their products, might be involved in controlling the intensity of CH and DTH responses. The direct injection of murine neutrophils, neutrophil homogenates, and a neutrophil granular fraction into the ear pinnae of normal mice resulted in a dosage-dependent ear-swelling reaction after 24 hours that was histologically similar to antigen-induced CH or DTH responses (primarily mononuclear cell infiltrate). Additional studies determined that an injection of elastase, collagenase, or peptides of elastin or collagen generated by elastase or collagenase treatment of insoluble elastin or collagen also caused a pronounced ear-swelling accompanied by a mononuclear cell infiltration. On the basis of these studies, coupled to experiments that demonstrated an inhibitory influence of alpha-1-antitrypsin (alpha 1-AT) on CH and DTH responses, we propose that neutrophil proteases may play an important role in regulating the intensity of CH and DTH responses in mice through their capacity to degrade extracellular matrix proteins whose peptide fragments are chemotactic for mononuclear cells and fibroblasts.
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PMID:The role of neutrophils in tissue localized cell-mediated immunologic responses: I. The intensity of contact-type and delayed-type hypersensitivity responses may be influenced by the extent of extracellular matrix degradation by neutrophil proteases. 285 42

Separation of lung alveolar basement membranes from interstitial connective tissue protein has proved difficult, and a pure preparation of alveolar wall basement membranes (AWBM) is not available. We have modified a technique employing the detergent Triton X-100 for isolating AWBM from rat lungs by adding a step utilizing human skin collagenase (HSC), a highly purified enzyme obtained from skin fibroblasts that specifically cleaves non-basement membrane collagens. Triton extraction of both lungs yields 15-20 mg of basement membrane-enriched material referred to as crude fraction (CF). Ultrastructural studies show that CF includes both epithelial and endothelial basement membranes that appear similar to their in vivo counterparts and contain heparan sulfate proteoglycans. Extraction of type IV collagen is documented by the appearance of highly glycosylated hydroxylysine. This CF contains minimal amounts of contaminating elastin but significant amounts of interstitial collagens. CF was further purified for biochemical studies by incubation with HSC. HSC solubilized 20% of CF hydroxyproline resulting in a final fraction highly enriched in AWBM. Lung minces incubated in tritiated lysine produced a CF extract rich in newly formed type IV collagen, showing that lung tissue synthesizes AWBM collagen in vitro.
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PMID:Isolation and characterization of a rat lung fraction enriched in alveolar wall basement membranes. 298 61

Studies were performed on 203 pairs of dog carotid arteries subjected to unidirectional radial compression. Treatment with 80 U/ml purified elastase for 90 min decreased radial stress, but treatment with 640 U/ml collagenase for 90 min did not. These data suggest that elastin, but not collagen, contributes to wall resistance to radial compression.
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PMID:Elastase, collagenase and the radial elastic properties of arteries. 299 Sep 92

The constituents of the connective tissues around the capillary of the chick pecten oculi were examined electron microscopically by HCl-collagenase and HCl-elastase methods. The basal lamina like membrane below the endothelial cell of the pecten capillary was digested by collagenases I, II and IV and elastase, and may be a false basal lamina. The basal lamina of cells with pigment granules which surround the capillary was digested by collagenase IV and elastase, and contained type IV collagen. Fibrils between the basal lamina like membrane of the pecten capillary endothelium and the basal lamina of the cells with pigment granules were digested by collagenases I, II and IV, and elastase. Thus, these fibrils are composed of many kinds of collagen. Elastase may be responsible for the breakdown of most collagens as well as elastin.
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PMID:Constituents of connective tissue around the capillary of chick pecten oculi. 299 47

A third metalloendopeptidase activity, gelatinase, has been completely separated from the collagenase and proteoglycanase activities of rabbit bone culture medium. Although the proteinase could not be purified to homogeneity in large amounts, it was possible to obtain accurate molecular weight values and activity after electrophoresis on non-reduced SDS/polyacrylamide gels. The latent form had an Mr of 65 000 which could be activated with 4-aminophenylmercuric acetate, APMA, to a form of Mr 61 000; under reducing conditions the latent and active forms had Mr of 72 000 and 65 000, respectively. Trypsin was a very poor activator of the latent enzyme. Gelatinase degraded gelatins derived from the interstitial collagens and it also had low activity on native types IV and V collagen and on insoluble elastin. Gelatinase acted synergistically with collagenase in degrading insoluble interstitial collagen. The specific mammalian tissue inhibitor of metalloproteinases inhibited gelatinase by forming a stable inactive complex. Comparison of the properties of gelatinase with those of collagenase and proteoglycanase suggest that the three proteinases form a family which together are capable of degrading all the major macromolecules of connective tissue matrices.
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PMID:Purification and characterization of a bone metalloproteinase that degrades gelatin and types IV and V collagen. 299 41

Rabbit synovial fibroblasts induced to undergo a specific switch in gene expression by agents that alter cell morphology secreted the neutral proteinase precursor procollagenase (apparent Mr of 53,000 and 57,000). A major Mr = 51,000 polypeptide that was always induced coordinately with procollagenase has now been identified as the proenzyme form of a metal-dependent proteinase active at neutral pH. We have named this proteinase stromelysin. Prostromelysin and procollagenase were the most prominent [35S]methionine-labeled secreted proteins of the induced fibroblasts. By the use of casein degradation as an assay for enzyme activity, stromelysin was isolated with high yield from the conditioned culture medium of 12-O-tetradecanoylphorbol 13-acetate-treated fibroblasts and migrated as an active form of Mr = 21,000 that was immunologically identical to the proteoglycan-degrading proteinase purified from rabbit bone. Immunoglobulin G from antiserum raised to purified rabbit bone proteoglycanase immunoprecipitated the Mr = 51,000 proenzyme form from conditioned medium of induced rabbit cells and also immunoprecipitated an Mr = 55,000 polypeptide from induced human fibroblasts. When rabbit prostromelysin was activated by trypsin or 4-aminophenylmercuric acetate, the proenzyme was converted to an active form of Mr = 41,000. During the course of the purification, prostromelysin was converted to an additional activatable form of Mr = 35,000 and additional active forms of Mr = 21,000-25,000, which had related peptide maps distinct from collagenase. All of these forms were immunologically cross-reactive. Purified stromelysin degraded casein, cartilage proteoglycans, fibronectin, alpha 1-proteinase inhibitor, and immunoglobulin G2a and had limited activity on laminin, elastin, type IV collagen, and gelatin, but did not degrade type I collagen. Stromelysin was inhibited by EDTA, 1,10-phenanthroline, and the specific glycoprotein tissue inhibitor of metalloproteinases isolated from human amniotic fluid and was therefore classified as a metalloproteinase.
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PMID:Stromelysin, a connective tissue-degrading metalloendopeptidase secreted by stimulated rabbit synovial fibroblasts in parallel with collagenase. Biosynthesis, isolation, characterization, and substrates. 299 74

The intense stromal response to some human tumors is termed the desmoplastic reaction. It is found with most human breast carcinomas. Dissolution of this response, containing predominantly fibrous proteins such as collagen and elastin, can occur with treatment. We have undertaken a study of the collagenases of the breast tumor desmoplastic reaction using a tissue culture model composed of human breast tumor cell lines and various human fibroblasts. The breast tumor cells had the higher collagenase activity, particularly the ZR75-31A cell line. Activity was 10-fold higher than that of the stromal cells. The enzyme was secreted into the media and required trypsin pretreatment for activity to be manifest. Partial purification was achieved of the major collagenase species. The protein was a metalloprotease and, like other mammalian collagenases, had a relative molecular weight of 60,000. Classical 3/4 and 1/4 cleavage products of the triple helical collagen substrate were demonstrated, typical of most mammalian collagenases. Only types I and III collagens were suitable substrates for this enzyme, with no apparent preference between the two. The breast tumor collagenases were not responsive to hormones; however, stimulation of activity was apparent in the absence of proteolytic pretreatment. This may represent conversion of the procollagenases of the breast tumor cells to the active form by an estrogen-sensitive plasminogen activator secreted by the same tumor cells.
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PMID:Collagenases in human breast carcinoma cell lines. 300 15

In an attempt to clarify the roles of proteases in the developmental mechanisms of hypertensive vascular lesions, changes in activities of aortic elastase, collagenase, and cathepsin D in spontaneously hypertensive rats (SHR) and renal hypertensive rats were biochemically investigated. In SHR, elastase activity initially showed a significant increase, once two-fold higher than that in the control; but the activity tended to decrease earlier than that in the control. In both SHR and normotensive control rats collagenase activities tended to increase with advancing age. The activity in SHR was two-fold higher than that in the control at all ages examined. In both younger SHR and normotensive rats cathepsin D activities proved to be increased with advancing age, while in old rats the activities tended to decrease. The activity in SHR was three- to fivefold higher than that in the control at all ages examined. In renal hypertensive rats, the activities of elastase, collagenase, and cathepsin D increased gradually with increasing blood pressure, at levels significantly higher than those in the control. These findings suggest that the metabolisms of proteins such as elastin and collagen, expressed by these enzyme activities, are accelerated under hypertensive conditions.
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PMID:Elastase, collagenase, and cathepsin D activities in the aortas of spontaneously hypertensive and renal hypertensive rats. 300 14


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