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

---

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

The basal levels of mRNAs encoding two metalloproteinases, collagenase and stromelysin, were increased as a function of in vitro serial subcultivation (cellular aging) of human fibroblasts. Procollagenase and prostromelysin synthesis and secretion were also greater in the old cultures (late passage). In contrast, the steady-state expression of mRNA for an inhibitor of metalloproteinases, tissue inhibitor of metalloproteinase-1 (TIMP-1), in late-passage cultures was lower than that in young cell cultures (early passage). Each mRNA was analyzed using total RNA preparations isolated from normal fibroblast cultures at different phases of the in vitro life span and from cultures derived from donors with the premature senescence syndromes characterized as Werner syndrome, progeria (Hutchinson-Gilford) syndrome, or Cockayne syndrome. In normal cell cultures expression of metalloproteinase mRNAs was increased after the culture had completed greater than 90% of the in vitro life span, and the reduction in TIMP-1 mRNA expression occurred after the culture had completed greater than 74% of the in vitro lifespan. In Werner syndrome cultures expression of metalloproteinase and TIMP-1 mRNAs was similar to the level of expression observed in late-passage cell cultures. Levels of metalloproteinase and TIMP-1 mRNA expression in progeria and Cockayne syndromes were similar to those of early-passage cell cultures. To determine if young and old cells were each responsive to mediators of metalloproteinase synthesis, cultures were treated with phorbol ester or cytokines. 12-O-tetradecanoylphorbol-13-acetate treatment increased the steady-state levels of all three mRNAs in young, old, and Werner syndrome cultures and increased procollagenase levels in all cultures. Early- and late-passage cell cultures also responded to cytokines. Interleukin-1 alpha treatment increased collagenase and stromelysin mRNA levels while transforming growth factor-beta reduced the steady-state levels of both transcripts. Neither cytokine affected the steady-state level of TIMP-1 mRNA. The results indicate that in vitro cellular aging is associated with changes in expression of mRNAs encoding proteins that mediate inflammatory responses and connective tissue remodeling.
...
PMID:Differential expression of metalloproteinase and tissue inhibitor of metalloproteinase genes in aged human fibroblasts. 132 16

Synovial fluid basic calcium phosphate crystals (BCP) are often found in severely degenerated joints. Crystalline BCP is a growth factor stimulating fibroblast mitogenesis and acting as a competence factor similar to platelet-derived growth factor. In human fibroblasts (HF), the synthesis of collagenase and stromelysin is coordinately induced after stimulation with a variety of cytokines and growth factors. We sought to determine whether BCP, like other growth factors, might induce proteases that would damage articular tissue. Northern blot analysis of mRNA for collagenase and stromelysin in HF stimulated with BCP was performed. Secreted enzymes were analyzed by immunoblot using a monoclonal antibody to collagenase and by immunoprecipitation using a polyclonal antibody to stromelysin. Stromelysin activity was confirmed using casein substrate gels. A significant, dose-dependent accumulation of collagenase and stromelysin message was evident after 4 h and continued for at least 24 h in BCP-stimulated cultures. Forty-nine and 54 kD proteins immunoreacting with collagenase antibody were identified in the conditioned media (CM) from BCP-stimulated cultures while 50 and 55 kD proteins were identified by immunoprecipitation with stromelysin antibody. Collagenase activity was increased significantly in the CM from BCP treated cells; casein substrate gels showed casein degrading bands at molecular weights consistent with stromelysin. BCP stimulates coordinate induction of collagenase and stromelysin which may mediate the joint destruction associated with these crystals.
...
PMID:Basic calcium phosphate crystals cause coordinate induction and secretion of collagenase and stromelysin. 132 76

The vEts oncoprotein and its progenitor cEts1(p68) belong to a growing family of transcription factors that are related by the conserved ets domain. We show here that the ets domain and adjacent COOH-terminal amino acids are required for DNA binding by cEts1(p68). vEts differs from cEts1(p68) in both the COOH-terminal sequence and an amino acid substitution in the ets domain. The change in the COOH-terminal sequence markedly decreases its affinity for specific DNA, and the ets domain mutation further diminishes binding. vEts does not trans-activate through the ets (PEA3) motif in vivo. Surprisingly, vEts still efficiently trans-activates the promoters of two genes, stromelysin and collagenase, that are found to be overexpressed in transformed cells. The AP1 motifs of both promoters are required for efficient activation. vEts does not bind to the AP1 motif, even in the presence of cJun and cFos. The DNA-binding domain of Ets1 is required for activation through the AP1 element. Activation is inhibited by the expression of the glucocorticoid and retinoic acid receptors, suggesting that activation by Ets does not involve reversal of negative regulators of AP1. We suggest that activation is by an indirect mechanism involving activation of endogenous genes. Our results show that vEts differs from its progenitor cEts1(p68) in its trans-activating properties. The findings suggest that activation of the Jun and Fos oncoprotein pathway is important for transformation by Ets.
...
PMID:Oncogenic conversion alters the transcriptional properties of ets. 132 27

Collagenase production by rodent osteoblasts in response to calciotropic hormones has led to the hypothesis that bone cells play a major role in bone resorption by degrading the surface osteoid layer, thereby exposing the underlying mineralized matrix to osteoclastic action. Many studies suggest, however, that this model might not apply to bone resorption in the human. Human osteoblasts have been shown to produce gelatinase-A (72 kDa) and TIMP-1 (tissue inhibitor of metalloproteinases), but previous investigators have been unable to demonstrate the synthesis of collagenase by human osteoblasts either constitutively or in response to bone resorptive agents. In the present study the ability of human osteoblasts to produce the matrix metalloproteinases (MMPs) collagenase, gelatinase and stromelysin, and their specific inhibitors TIMPs-1 and 2, was examined using highly sensitive and specific antisera and by zymography. Semi-quantitative histomorphometric data showed that cells cultured on either glass or a type I collagen substratum constitutively synthesized gelatinase-A and TIMP-1. On type I collagen, however, a small proportion of unstimulated cells produce both collagenase (7%) and gelatinase-B (95 kDa; 3%). Treatment of cells with either parathyroid hormone (PTH), 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3), or partially purified mononuclear cell conditioned medium (MCM), stimulated the synthesis of collagenase, gelatinase-B and stromelysin; MCM was 2- to 3-fold more potent than either PTH or 1,25(OH)2D3. Zymography using SDS/PAGE on conditioned media from cells cultured on type I collagen films revealed the presence of active gelatinase-A and that MCM stimulated progelatinase-B synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Human osteoblasts in culture synthesize collagenase and other matrix metalloproteinases in response to osteotropic hormones and cytokines. 133 77

This study was performed to characterize the matrix metalloproteinases (MMPs) produced during the degradation of cotton-wrapped cartilage, implanted into the murine air pouch. One, two or three weeks following cartilage implantation, proteins were extracted from the granulation tissue and MMP activities were measured. Although collagenase-, gelatinase- and stromelysin-like activities were detected at each time point, gelatinase activity was by far the most prominent. These enzymes were inhibited by EDTA, but not by NEM or PMSF, indicating that these proteinases were metalloproteinases. Gelatin zymography revealed several lysis zones amongst which a major 92-kDa band shifted to 83- and 68-kDa species during the course of implantation. The emergence of these species coincided with enhanced gelatinolytic activity and collagen loss from the implanted cartilage.
...
PMID:Gelatinase is the main matrix metalloproteinase involved in granuloma-induced cartilage degradation. 133 18

The interstitial collagenase gene (CLG), one of the main candidates in severe generalized recessive epidermolysis bullosa dystrophica (SGREBD), is closely linked to the stromelysin-1 (STMY1) and stromelysin-2 (STMY2) genes. These three loci map on chromosome 11 (q21-q22.3), where they constitute a cluster of genes coding for metalloproteinases involved in the degradation of the extracellular matrix (ECM). A recessive form of cerebellar ataxia of post-puberal onset (CLA1) has also been assigned to chromosome 11 (q14-q21). Since useful restriction fragment length polymorphisms (RFLPs) for the CLG gene are not available, we have studied the inheritance of the marker TaqI RFLP of the STMY1 gene in a North Italian family with a child affected by SGREBD, and his two sisters showing cerebellar ataxia (CA) of post-puberal onset. We have also studied the MspI RFLP of the fibronectin gene (FN1), which is located on chromosome 2q34-q36, and which codes for non-collagenous matrix proteins. Since we did not observe the segregation of the pathological phenotypes with STMY1 and FN1 RFLPs, we excluded the involvement of these genes in both the SGREBD and CA present in this family. The exclusion of the STMY1 gene indicates that the mutation causing SGREBD cannot be located in the CLG and/or STMY2 genes because of their proximity to the STMY1 locus. These data also indicate that the CA form here reported is not attributable to alterations in regions close to the collagenase cluster on chromosome 11.
...
PMID:Exclusion of stromelysin-1, stromelysin-2, interstitial collagenase and fibronectin genes as the mutant loci in a family with recessive epidermolysis bullosa dystrophica and a form of cerebellar ataxia. 135 52

The c-ets1 proteins are transcriptional activators expressed within endothelial cells during blood vessel development in chick embryos. The authors show by in situ hybridization that c-ets1 is transcribed in the endothelia during angiogenesis in human embryos, in granulation tissue, and especially during tumor vascularization. c-ets1 mRNAs were also detected in the fibrocytes of tumor stroma and in the spindle cells of Kaposi's sarcomas, regarded as cells of endothelial origin. It has been shown that the c-ets proteins activate transcription through a PEA3 motif that plays a role in the stimulation of transcription of urokinase-type plasminogen-activator (u-PA), stromelysin and collagenase genes. The authors demonstrate in vitro that the angiogenic factor TNF alpha increases transiently the amount of both c-ets1 and u-PA mRNA in confluent human umbilical vein endothelial cells. Therefore, the authors suggest that the c-ets1 proteins might regulate the transcription of the genes coding for matrix-degrading proteases, which are necessary for both angiogenesis and tumor invasion.
...
PMID:c-ets1 proto-oncogene is a transcription factor expressed in endothelial cells during tumor vascularization and other forms of angiogenesis in humans. 137 May 94

The effects of the chondroprotective drugs, sodium pentosan polysulphate (SP54) and Arteparon (glycosaminoglycan polysulphate), on the in vitro activities of the purified matrix metalloproteinases interstitial collagenase (matrix metalloproteinase 1, MMP1) and stromelysin (MMP3) were examined. Both drugs produced concentration-dependent enhancement of the degradation of type I collagen fibrils by purified human fibroblast collagenase and rat tumour collagenase. Rat collagenase activity was increased by drug concentrations above 0.5 microgram/mL, whereas human collagenase activity was only increased by higher drug concentrations, above 5 micrograms/mL. The concentration dependence of the increase in rat collagenase activity was similar for both drugs, with a maximal 3-fold increase at 50 micrograms/mL. In contrast, human collagenase activity was increased to a greater extent by SP 54 compared to Arteparon, with maximal increases at 5000 micrograms/mL of 6-fold and 2-4-fold, respectively. Both drugs produced concentration-dependent inhibition of the proteoglycan-degrading activity of both human fibroblast stromelysin and rat tumour stromelysin. Rat and human stromelysin activities were inhibited at drug concentrations above 0.005 microgram/mL, with a similar concentration dependence for both drugs. Fifty percent inhibition of rat stromelysin was produced by concentrations of each drug in the 0.5-5 microgram/mL range. The pattern of inhibition of human stromelysin was similar, except that drug concentrations in the 500-5000 micrograms/mL range produced 50% inhibition. The possible modes of action for these drug effects and their possible pharmacological significance are discussed.
...
PMID:The chondroprotective drugs, Arteparon and sodium pentosan polysulphate, increase collagenase activity and inhibit stromelysin activity in vitro. 138 3

Matrix metallo-proteinases (MMPs) are a group of enzymes thought to be responsible for both normal connective tissue matrix remodelling and accelerated breakdown associated with tumor development. The distribution of 3 major matrix metallo-proteinases was studied in human mammary pathology: collagenase (MMP1) which degrades fibrillar interstitial collagens, a 72-kDa gelatinase (MMP2) which mainly degrades type IV collagen and denatured collagens, and stromelysin (MMP3) which has a wider range of action, degrading several matrix components including the core proteins of proteoglycans, laminin and non-helical regions of collagens. These MMPs and the MMP tissual inhibitor (TIMP1) were detected by immunohistochemistry in 30 benign and 79 malignant lesions of the breast. MMPs were detected in 1 fibroadenoma (collagenase) and 22 breast carcinomas: collagenase (9 cases), stromelysin (12 cases) and gelatinase (16 cases) with a limited distribution. Tumor cells were preferentially labelled and the localization of gelatinase and stromelysin at the periphery of some non-invasive and well-differentiated clusters supports the role of these enzymes in the breakdown of basement membranes. Only a few stromal cells (fibroblasts) were found to be immunopositive. In contrast, TIMP1 was more frequently detected, and was found in 7 benign lesions and 55 carcinomas out of 79. It was mainly localized at the periphery of the endothelial cells but was occasionally detected in cancer cells and fibroblasts.
...
PMID:Immunolocalization of matrix metallo-proteinases and their tissue inhibitor in human mammary pathology. 139 65

Matrix metalloproteinase 9 (MMP-9) has been purified as an inactive zymogen of M(r) 92,000 (proMMP-9) from the culture medium of HT 1080 human fibrosarcoma cells. The NH2-terminal sequence of proMMP-9 is Ala-Pro-Arg-Gln-Arg-Gln-Ser-Thr-Leu-Val-Leu-Phe-Pro, which is identical to that of the 92-kDa type IV collagenase/gelatinase. The zymogen can be activated by 4-aminophenylmercuric acetate, yielding an intermediate form of M(r) 83,000 and an active species of M(r) 67,000, the second of which has a new NH2 terminus of Met-Arg-Thr-Pro-Arg-(Cys)-Gly-Val-Pro-Asp-Leu-Gly-Arg-Phe-Gln-Thr- Phe-Glu. Immunoblot analyses demonstrate that this activation process is achieved by sequential processing of both NH2- and COOH-terminal peptides. TIMP-1 complexed with proMMP-9 inhibits the conversion of the intermediate form to the active species of M(r) 67,000. The proenzyme is fully activated by cathepsin G, trypsin, alpha-chymotrypsin, and MMP-3 (stromelysin 1) but not by plasmin, leukocyte elastase, plasma kallikrein, thrombin, or MMP-1 (tissue collagenase). During the activation by MMP-3, proMMP-9 is converted to an active species of M(r) 64,000 that lacks both NH2- and COOH-terminal peptides. In addition, HOCl partially activates the zymogen by reacting with an intermediate species of M(r) 83,000. The enzyme degrades type I gelatin rapidly and also cleaves native collagens including alpha 2 chain of type I collagen, collagen types III, IV, and V at undenaturing temperatures. These results indicate that MMP-9 has different activation mechanisms and substrate specificity from those of MMP-2 (72-kDa gelatinase/type IV collagenase).
...
PMID:Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080 human fibrosarcoma cells. Purification and activation of the precursor and enzymic properties. 140 Apr 81


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---