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)

A 33-year-old man presented with a spontaneous progressive cutaneous tumor-like fibrosis involving the right leg and buttock. Histologically the deep dermis was composed of numerous fibroblasts and dense bands of collagen, suggesting that the lesion might be related to an abnormality in collagen metabolism. Fibroblast cultures were established from the affected and normal-appearing skin. The growth rate of the lesional cells was essentially equal to that of control cells. The synthesis of procollagen was approximately 3.5-fold increased in the cells derived from the nodules when compared with control fibroblasts (p less than 0.001). The increase in procollagen synthesis was reflected by an approximate 6-fold increase in both type I and type III procollagen mRNA abundance in the lesional fibroblasts (p less than 0.001), thus suggesting an aberration in the pretranslational level of procollagen gene expression. In contrast, the synthesis of collagenase, the enzyme required for the initiation of collagen degradation, was decreased to approximately 25% of control values (p less than 0.0025), although the enzyme was catalytically normal. The data indicate that these cells are characterized by an increased synthesis of procollagen and decreased synthesis of collagenase, 2 phenotypic characteristics that could account pathophysiologically for the lesions. The unusual reciprocal nature of these biochemical parameters in 2 proteins important in connective tissue homeostasis suggests that this progressive tumor-like condition may have resulted from the expansion of a clonal population of cells.
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PMID:Progressive nodular fibrosis of the skin: altered procollagen and collagenase expression by cultured fibroblasts. 301 1

The role of indomethacin in the regulation of extracellular matrix synthesis was studied in dermal fibroblast cultures. Indomethacin (10 microM) blocked totally the prostaglandin secretion and markedly increased the synthesis of collagen. In parallel, measurement of fibronectin, type I and type III procollagen mRNA levels showed a substantial increase under the action of indomethacin. On the other hand, indomethacin did not modify the mRNA levels of dermatan sulfate proteoglycan core protein. Measurement of collagen production estimated as the amount of collagenase digestible protein and by specific radioimmunoassay indicated a good correlation with the corresponding mRNA levels. These results suggest that indomethacin can regulate the extracellular matrix deposition at a transcriptional level.
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PMID:Gene expression of fibroblast matrix proteins is altered by indomethacin. 336 Jan 17

The N-terminal propeptide of type III procollagen was purified from human ascitic fluid by using (NH4)2SO4 precipitation, DEAE-Sephacel chromatography at pH 8.6, Sephacryl S-300 chromatography and another DEAE-Sephacel chromatography at pH 4.5. The Mr of the human peptide was about 42 000, which corresponds in size to the propeptide released by the specific N-proteinase during the extracellular processing of collagen. Bacterial-collagenase digestion of the human peptide produced three fragments, which could be separated on a Bio-Gel P-10 column. The human propeptide and its collagenase-derived fragments, an N-terminal non-collagenous domain Col 1, a C-terminal non-helical domain Col 2 and a collagenous domain Col 3, resembled those derived from the N-terminal segment of bovine type III procollagen in their amino acid composition. The human peptide was found to contain sulphate, which may explain its extremely low isoelectric point (3.1). Antibodies against the human N-terminal propeptide reacted similarly with both the purified human peptide and a corresponding segment of bovine type III procollagen. The human propeptide could be used in developing radioimmunoassays for monitoring fibrotic processes.
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PMID:Purification and characterization of the N-terminal propeptide of human type III procollagen. 408 23

The effect of 17 beta-estradiol (E2) on the biosynthesis of collagen in cultured bovine aortic smooth muscle cells was explored. Cells treated with various concentrations of the hormone for 14 days following subcultivation were subjected to growth studies. The cultures were also evaluated for [14C]hydroxyproline formation, the presence of collagenase-susceptible protein, prolyl hydroxylase activity, and procollagen types. There were no effect of E2 on the growth of these cells. At 10(-8) M E2, the hydroxylation of proline when compared to control cultures was reduced by 25-30%; however, little difference in extractable prolyl hydroxylase activity or total [14C]proline incorporation into protein was observed. The effect on collagen synthesis appears to be dose dependent over concentrations of E2 ranging from 10(-6) to 10(-12) M when measured by collagenase susceptibility. Procollagen typing on diethylaminoethylcellulose displayed reduced amounts of procollagen type I and type III fractions as well as other collagenous components. More importantly, however, the ratio of these two procollagen types were also altered. Similar results were obtained from the medium or cell layer. It is concluded that aortic smooth muscle cells cultured in the presence of 17 beta-estradiol display a decreased production of collagen in addition to altering the ratio of type I to type III procollagen fractions produced.
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PMID:Effects of 17 beta-estradiol on the biosynthesis of collagen in cultured bovine aortic smooth muscle cells. 626 9

A 10-yr-old female presented with cerebriform tumors covering the plantar surfaces of both feet. Histologically, the lesions consisted of thick collagen fibers and the content of collagen per surface area of skin was increased about 8-fold. Examination of the collagen by SDS-polyacrylamide gel electrophoresis, after limited pepsin proteolysis, showed that the lesions consisted almost exclusively of type I collagen, the predominant collagen type in human skin. Thus, a diagnosis of connective tissue nevi of the collagen type was made. Fibroblast cultures were established from the affected and normal-appearing areas of the skin, and examined for the rate of collagen synthesis, production of collagenase and growth kinetics of the cells. Cell cultures derived from the lesion and from control skin synthesized procollagen at the same rate and in a normal type I/type III procollagen ratio. However, the production of enzymatically active and immunologically detectable collagenase was reduced by 70-82% in the cultures derived from the lesion as compared to controls (p less than 0.005). Fibroblasts derived from the lesions also displayed a mean population doubling time of 1.17 +/- 0.08 days compared to 1.83 +/- 0.24 and 1.92 +/- 0.09 days for control cell strains and cells derived from normal skin of the patient, respectively (p less than 0.025). These results suggest that the excessive deposition of collagen in this case may have resulted from decreased local degradation of collagen. Enhanced proliferative capacity of the regional fibroblasts may have contributed to the accumulation of collagen in these lesions.
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PMID:Decreased collagenase production by regional fibroblasts cultured from skin of a patient with connective tissue nevi of the collagen type. 627 72

We studied the extracellular localization of factor VIII-related antigen (VIIIR: Ag) in cultures of human endothelial cells. The cells deposited both VIIIR: Ag and fibronectin already during their initial adhesion phase and in immunofluorescence microscopy of spread cells extracellular VIIIR: Ag was localized to fibrils coaligning with pericellular fibronectin. When human fibroblasts, which do not synthesize VIIIR: Ag, were cultured in endothelial cell post-culture medium, a fibrillar matrix localization of VIIIR: Ag was seen, comparable to that of endothelial cell cultures. A fibrillar VIIIR: Ag-specific staining was also seen in cell-free pericellular matrices of endothelial cells, produced by deoxycholate treatment. In immunoelectron microscopy, VIIIR: Ag was seen in fibrillar extracellular material between and underneath the cells and in cell-free matrices of of endothelial cells as well. In immunofluorescence microscopy of cell-free matrices, VIIIR: Ag codistributed with both fibronectin and type III procollagen. Digestion of the matrices with purified bacterial collagenase abolished the type III procollagen-specific fluorescence, whereas the fibrillar VIIIR: Ag-specific staining, codistributing with fibronectin, remained unaffected. In electrophoresis of isolated, metabolically labelled endothelial cell matrices, major polypeptides with Mr 220-240; 180; 160 and 45 kD and some minor polypeptides were resolved. In addition, immunoblotting revealed fibronectin, VIIIR: Ag and type III procollagen as components of cell-free matrices of endothelial cells. Direct overlay of iodinated cellular fibronectin on electrophoretically separated polypeptides of cultured endothelial cells, transferred to nitrocellulose, suggested that fibronectin binds directly to VIIIR: Ag. Our results indicate that VIIIR: Ag produced by human endothelial cells is a component of the pericellular matrix and is not bound to collagen but may directly associate with fibronectin.
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PMID:Factor VIII-related antigen. A pericellular matrix component of cultured human endothelial cells. 631 62

The N-terminal extension peptide of type III procollagen, isolated from foetal-calf skin, contains 130 amino acid residues. To determine its amino acid sequence, the peptide was reduced and carboxymethylated or aminoethylated and fragmented with trypsin, Staphylococcus aureus V8 proteinase and bacterial collagenase. Pyroglutamate aminopeptidase was used to deblock the N-terminal collagenase fragment to enable amino acid sequencing. The type III collagen extension peptide is homologous to that of the alpha 1 chain of type I procollagen with respect to a three-domain structure. The N-terminal 79 amino acids, which contain ten of the 12 cysteine residues, form a compact globular domain. The next 39 amino acids are in a collagenase triplet sequence (Gly- Xaa - Yaa )n with a high hydroxyproline content. Finally, another short non-collagenous domain of 12 amino acids ends at the cleavage site for procollagen aminopeptidase, which cleaves a proline-glutamine bond. In contrast with type I procollagen, the type III procollagen extension peptides contain interchain disulphide bridges located at the C-terminus of the triple-helical domain.
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PMID:Complete amino acid sequence of the N-terminal extension of calf skin type III procollagen. 633 92

Pulmonary artery endothelial cells were isolated from bovine fetal blood vessels and used for biosynthetic studies. At confluence, cultures were incubated in minimal essential medium (MEM) without serum containing [U-14C]proline. After 24 hours, medium was removed and labeled proteins were precipitated by the addition of ammonium sulfate and fractionated by diethylaminoethyl (DEAE)-cellulose chromatography. The elution profile showed four major peaks and one minor peak. Fractions within each peak were pooled, subjected to digestion by chymotrypsin and/or collagenase, and analyzed by polyacrylamide gel electrophoresis. Peak l contained a collagen which contained approximately 6% of the 3-hydroxyproline isomer while total hydroxyproline content was approximately 45%. This material was digested by purified bacterial collagenase and had a mobility slightly slower than that of alpha 1(III) which did not change under conditions that reduce disulfide bonds. Upon digestion with chymotrypsin under conditions where native procollagens are converted to alpha-chains, this material was digested. These properties suggest that this material is type VIII or EC (endothelial cell) collagen. Peak 2 contained substantial fibronectin while peak 3 contained primarily type III procollagen. The last major peak contained a mixture of collagenous and noncollagenous material. Upon digestion with chymotrypsin, several peptides were generated which were sensitive to bacterial collagenases. The two major chymotrypsin-resistant components had mobilities slower than that of alpha(III) and were not disulfide-bonded.
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PMID:Collagen synthesis by cloned pulmonary artery endothelial cells. 671 15

The processing of type III and type I procollagen molecules in cultured bovine aortic smooth muscle cells was investigated. The molecular identities of the processing intermediates of type III and type I procollagen were characterized by analysis of the radioactive collagenous components using mammalian collagenase and pepsin digestions and cyanogen bromide peptide mapping. The results indicate that the processed intermediates for procollagen type III and type I are their respective pC components. Although the processing pathways for both collagen types are the same, data from pulse-chase experiments suggest that the rates at which the processing occurs are different. Type I procollagen is processed more rapidly to its intermediate than is type III procollagen. The type I pC intermediate is almost completely processed to alpha-chains and a significant portion of these fully processed molecules remains in a soluble form even after 11 h. In the same time period, the type III pC intermediate is slowly converted to alpha-chains. Since beta-aminopropionitrile was not employed in these studies, significant accumulation of collagen chains into the insoluble extracellular matrix was observed during the chase period.
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PMID:Processing of procollagen types III and I in cultured bovine smooth muscle cells. 674 44

Fibroblasts from normal human subjects and from a patient who had osteogenesis imperfecta were incubated with [3H]mannose, and types I and III procollagens were isolated from the culture medium. The type I procollagen from the patient's fibroblasts contained 2-3 time more [3H]mannose than the type I procollagen from the normal fibroblasts. In contrast, there was no difference in the [3H]mannose content of the type III procollagen simultaneously synthesized and secreted by the same cells. Isolation of a collagenase-resistant peptide fragment from the type I procollagen showed that the excess mannose was located in the COOH-terminal propeptide of the protein. Radioimmunoassays of the medium and the cell layer showed that the type I procollagen synthesized by the patient's fibroblasts was secreted into the medium more slowly than the type I procollagen synthesized by normal fibroblasts. These results appear to provide evidence for an alteration in the structure of procollagen in osteogenesis imperfecta.
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PMID:A defect in the structure of type I procollagen in a patient who had osteogenesis imperfecta: excess mannose in the COOH-terminal propeptide. 693 45


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