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)

Membrane-type matrix metalloproteinase (MT-MMP), which we have identified recently, is unique in its transmembrane (TM) domain at the C terminus and mediates activation of pro-gelatinase A on the cell surface (Sato, H., Takino, T., Okada, Y., Cao, J., Shinagawa, A., Yamamoto, E., and Seiki, M. (1994) Nature 370, 61-65; Takino, T., Sato, H., Yamamoto, E., and Seiki, M. (1995) Gene (Amst.) 115, 293-298). In addition to MT-MMP, a novel MMP-related cDNA of 2.1 kilobases was isolated from a human placenta cDNA library. The cDNA contains an open reading frame for a new MMP. The deduced protein composed of 604 amino acids was closely related to MT-MMP in the amino acid sequence (66% homology at the catalytic domains) and has a potential TM domain at the C terminus. Monoclonal antibodies raised against the synthetic peptide recognized a 64-kDa protein as the major product in the transfected cells. TIMP-1 fused with the potential TM domain was localized on the cell surface while native TIMP-1 is in the culture medium. Thus, we called the second membrane-type MMP, MT-MMP-2 and renamed MT-MMP, MT-MMP-1. MT-MMP-1 and -2 are thought to form a distinct membrane-type subclass in the MMP family since all the others are secreted as soluble forms. Like MT-MMP-1, expression of MT-MMP-2 induced processing of pro-gelatinase A (68-kDa in gelatin zymography) into the activated form of 62-kDa fragments through a 64-kDa intermediate form. Expression of MT-MMP-2 mRNA was at the highest levels in the brain where MT-MMP-1 was at the lowest level compared to other tissues. MT-MMP-1 and -2 are thought to be utilized for extracellular matrix turnover on the surface of cells under different genetic controls.
...
PMID:Identification of the second membrane-type matrix metalloproteinase (MT-MMP-2) gene from a human placenta cDNA library. MT-MMPs form a unique membrane-type subclass in the MMP family. 755 40

Loss of negative growth regulation and high invasive potential are neoplastic traits often associated with abnormal expression of matrix metalloproteinases (MMPs). We previously found MMP-3 (stromelysin/transin) was secreted by quiescent rat Schwann cell cultures and expressed potent antiproliferative activity. In the present study we observed that human Schwann cells and cutaneous neurofibroma Schwann cell cultures secreted abundant MMP-3 and their proliferation was inhibited by autologous and rat Schwann cell conditioned media. Antiproliferative activities were depleted by immunoadsorption with anti-stromelysin antibodies. In contrast, plexiform neurofibroma cultures did not secrete MMP-3 and failed to respond to Schwann cell antiproliferative activities associated with MMP-3. Quiescent Schwann cells constitutively secreted low levels of MMP-2 (gelatinase A) and showed a low invasion potential in filter-based assays of basement membrane invasion. Cyclic AMP elevation, which profoundly influences cell differentiation, increased the invasion potential of rat Schwann cells and caused a corresponding increase in secretion of MMP-2. Schwann cells immortalized by protracted elevation of cAMP, as well as a schwannoma cell line (D6P2T), also rapidly invaded a reconstituted basement membrane and over-expressed MMP-2. Similarly, neurofibroma Schwann cells were highly invasive and secreted up to 10-fold more MMP-2 than normal human Schwann cells. Additionally, only cutaneous neurofibroma Schwann cell cultures secreted MMP-9 (gelatinase B) and MMP-1 (interstitial collagenase) and also invaded native type I collagen barriers. Cultures of normal Schwann cells and plexiform neurofibroma tumor expressed little or no MMP-1 and did not invade type I collagen barriers. These results suggest a role for MMPs in the control of proliferation and invasion by Schwann cells and in the formation of peripheral nerve sheath tumors.
...
PMID:Differences in proliferation and invasion by normal, transformed and NF1 Schwann cell cultures are influenced by matrix metalloproteinase expression. 760 93

The activity of type I and IV collagenase was measured in thyroid tissue obtained from 6 non-diseased thyroids, 4 patients with Graves' diseases, 5 with follicular adenoma, 6 with papillary carcinoma and 4 with follicular carcinomas. The relationship between these enzyme activities and invasion or metastasis of the original tumors was studied. The activity of type I collagenase in papillary carcinomas and follicular carcinomas was higher than in non-diseased thyroids, Graves' disease and follicular adenoma. Carcinoma tissue with invasion beyond the capsule in particular had higher type I collagenase activity. Type IV collagenase activity in carcinoma with lymph node metastasis was higher than in non-diseased thyroids, Graves' disease and follicular adenoma, and especially higher than carcinoma without lymph node metastasis. These findings suggest that increased type I collagenase activity plays an important role in local invasion in thyroid carcinoma, and that increased type IV collagenase activity plays an important role in lymph node metastasis.
...
PMID:[Study of type I and IV collagenase activity in human thyroid diseases]. 762 46

Antibodies were raised against seven major matrix metalloproteinases: stromelysin-1 (MMP-3), stromelysin-2 (MMP-10), stromelysin-3 (MMP-11), interstitial collagenase (MMP-1), M(r) 72,000 type IV collagenase (72 kDa type IV collagenase, MMP-2), M(r) 92,000 type IV collagenase (92 kDa type IV collagenase, MMP-9) and matrilysin (PUMP, MMP-7) as well as against prolyl 4-hydroxylase, to study the expression of these collagenolytic enzymes in normal liver in relation to the activity of collagen synthesis. Tissue samples of four normal human livers, three hepatocellular carcinomas and one cholangiocellular carcinoma were analysed. In normal liver we found expression of stromelysin-1, stromelysin-3, interstitial collagenase, M(r) 72,000 and M(r) 92,000 type IV collagenases and varying expression of prolyl 4-hydroxylase. Stromelysin-2 was inconsistently detectable; matrilysin was not found. In hepatocellular carcinoma the expression pattern of matrix metalloproteinases showed only minor changes compared with the normal tissue; stronger signals than in normal tissue were seen for stromelysin-1, and stromelysin-2 was also strongly positive. M(r) 72,000 and M(r) 92,000 type IV collagenases and interstitial collagenase were less strongly expressed; stromelysin-3 was unchanged. Expression of prolyl 4-hydroxylase was also increased compared with normal liver. Matrilysin was only seen in cholangiocellular carcinoma, which showed a completely different pattern of matrix metalloproteinase expression. Our results show that metalloproteinases are expressed in human liver with much greater abundance than previously described. Their expression pattern is not changed fundamentally in hepatocellular carcinoma but is completely different from that of other tumour tissues such as cholangiocellular carcinoma.
...
PMID:Expression pattern of matrix metalloproteinases in human liver. 763 22

Pancreatic cancer shows a strong desmoplastic reaction characterized by a remarkable proliferation of interstitial connective tissue (collagens type I and III, fibronectin). In this study we have analyzed the balance of expression of mRNAs encoding extracellular matrix components (collagens I, III and IV, laminin, fibronectin), extracellular matrix-degrading metalloproteinases (MMP-1, -2, -3 and -9) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in pancreatic cancer and control pancreatic tissue by Northern-blot analysis and mRNA in situ hybridization. Transcripts for MMP-1 (interstitial collagenase) and MMP-3 (stromelysin-1) were not detectable in pancreatic cancer and control tissues. Steady-state levels of transcripts encoding extracellular matrix proteins, MMP-2 (72-kDa collagenase IV), MMP-9 (92-kDa collagenase type IV), TIMP-1 and TIMP-2 were elevated in the majority of pancreatic-cancer tissue samples as compared to control pancreatic tissue. A good correlation was seen between overexpression of these MMPs and TIMPs and the steady-state levels of transcripts coding for extracellular matrix proteins, the amount of collagen protein and the severity of the desmoplastic reaction. In situ hybridization studies localized transcripts coding for collagens type I and III to spindle-shaped stromal cells, whereas transcripts for MMP-2, MMP-9, TIMP-1 and TIMP-2 were found in both stromal and tumor cells. However, MMP-2 transcripts appeared to be more abundant in stromal cells, TIMP-1 and TIMP-2 transcripts were evenly distributed over tumor and stromal cells and relatively more MMP-9 transcripts were found in tumor cells. We conclude that, in human pancreatic cancer, MMP-2, MMP-9, TIMP-1 and TIMP-2 may be involved in processes leading to the strong desmoplastic reaction observed in these tumors. Both stromal and tumor cells appear to be the source of MMPs and TIMPs in human pancreatic cancer.
...
PMID:Expression and in-situ localization of genes coding for extracellular matrix proteins and extracellular matrix degrading proteases in pancreatic cancer. 763 66

The actions of human recombinant stromelysins-1 and -2, collagenase, gelatinases A and B and matrilysin on neonatal human proteoglycan aggregates were examined. With the exception of gelatinase B, aggrecan was degraded extensively by most metalloproteinases studied, whereas link protein showed only limited proteolysis. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Cleavage at the former bond generated a link protein component with the same N-terminus as that isolated from newborn human cartilage. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix.
...
PMID:Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. 769 69

We have compared the effects of a general matrix metalloproteinase (MMP) inhibitor (CT435) with those of a concentration-dependent specific gelatinase inhibitor (CT543; Ki < 20 nM) on bone resorption in vitro. The test systems consisted of measuring: (i) the release of 45Ca2+ from prelabelled mouse calvarial explants; (ii) the release of 45Ca2+ from prelabelled osteoid-free calvarial explants co-cultured with purified chicken osteoclasts; and (iii) lacunar resorption by isolated rat osteoclasts cultured on ivory slices. Both CT435 and CT543 dose-dependently inhibited the release of 45Ca2+ from neonatal calvarial bones stimulated by either parathyroid hormone or 1,25-dihydroxyvitamin D3. Moreover, CT543 produced a 40% inhibition at a concentration (10(-8) M) selective for the inhibition of human gelatinases A and B. CT435 (10(-5) M) and CT543 (10(-5) M) partially inhibited the release of 45Ca2+ from osteoid-free calvarial explants by chicken osteoclasts with a maximum of approximately 25% for unstimulated cultures, and approximately 36% for cultures stimulated by interleukin-1 alpha (IL-1 alpha; 10(-10) M). Neither inhibitor prevented lacunar resorption on ivory by unstimulated rat osteoclasts, but the compounds produced a partial reduction in both the number and total surface area of lacunae in IL-1 alpha-stimulated cultures, with maximal action at 10(-5) M. Neither of the inhibitors affected protein or DNA synthesis, nor the IL-1 alpha-stimulated secretion of the lysosomal enzyme beta-glucuronidase. Immunocytochemistry demonstrated that isolated rabbit osteoclasts constitutively expressed gelatinase A and synthesized gelatinase B, collagenase and stromelysin, as well as the tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) following IL-1 alpha stimulation. These experiments have shown that in addition to collagenase, gelatinases A and B are likely to play a significant role in bone resorption. They further suggest that MMPs produced by osteoclasts are released into the sub-osteoclastic resorption zone where they participate in bone collagen degradation.
...
PMID:The effects of selective inhibitors of matrix metalloproteinases (MMPs) on bone resorption and the identification of MMPs and TIMP-1 in isolated osteoclasts. 769 5

The expression of matrix-degrading metalloproteases (MMPs) by human skeletal muscle satellite cells was investigated by zymography of cell culture media and by Northern blot analysis of mRNA prepared from satellite cells. Zymography in gelatin substrate gels revealed that satellite cells constitutively synthesize and secrete 72 kDa gelatinase (MMP-2). In addition, treatment of satellite cell cultures with phorbol ester resulted in an induction of 92 kDa gelatinase (MMP-9) activity. On casein substrate gels, little or no proteolytic activity was detectable in control or phorbol ester treated satellite cell cultures, suggesting that compared to fibroblasts, satellite cells secrete little or no interstitial collagenase (MMP-1) or stromelysin (MMP-3) activity. Northern blotting, however, revealed that there is detectable expression of mRNA transcripts encoding MMP-1 in satellite cell cultures, and that increased accumulation of MMP-1 mRNA transcripts occurs upon treatment of these cells with phorbol ester. In contrast, no constitutive, or induced expression of transcripts encoding MMP-3 was detectable in satellite cells. These findings show that satellite cells can synthesize and secrete selected members of the MMP family and suggest that skeletal muscle cells may participate directly in remodelling of the extracellular matrix during myogenesis and the regeneration of skeletal muscle.
...
PMID:Synthesis and secretion of matrix-degrading metalloproteases by human skeletal muscle satellite cells. 770 24

Several members of the matrix metalloproteinase family have been reported to cleave aggrecan in the interglobular domain between Asn-341 and Phe-342. An antiserum was prepared against a peptide conjugate corresponding to the C-terminal sequence of the matrix metalloproteinase-generated aggrecan G1 fragment (Phe335-Val-Asp-Ile-Pro-Glu-Asn341). A quantitative radioimmunoassay, with a limit of detection of about 80 pM, was developed using this antiserum. This antiserum requires the free carboxyl group of the C-terminal asparagine for optimal recognition. If the C-terminal asparagine is excised from the sequence, replaced with closely related amino acids, or extended across the matrix metalloproteinase cleavage site, there is a 40-10,000-fold loss in detection. Using peptides cleaved from the N-terminus, it was determined that the antiserum requires the entire Phe-Val-Asp-Ile-Pro-Glu-Asn sequence for optimal recognition. The radioimmunoassay detects matrix metalloproteinase-generated G1 fragments with similar sensitivity to the Phe-Val-Asp-Ile-Pro-Glu-Asn peptide, but it does not recognize intact aggrecan. Immunoreactive aggrecan G1 fragments of molecular mass 50 kDa are generated by the matrix metalloproteinases stromelysin and gelatinase A. In contrast, under identical conditions, the closely related metalloproteinases, gelatinase B and collagenase, as well as cathepsin G, cathepsin B and human leucocyte elastase, did not generate a G1 fragment recognized by the antiserum. The anti-Phe-Val-Asp-Ile-Pro-Glu-Asn serum detects stromelysin-generated aggrecan G1 fragments from mouse, guinea pig, rabbit and human, indicating that the detection is not species-specific. This antiserum and radio-immunoassay should be useful for quantifying and characterizing matrix metalloproteinase-generated aggrecan G1 fragments in articular cartilage and synovial fluids from humans and various animal models of articular-cartilage destruction.
...
PMID:Quantification of a matrix metalloproteinase-generated aggrecan G1 fragment using monospecific anti-peptide serum. 771 83

A leupeptin analogue, pyroglutamyl-Leu-Arg-CHO (Pyr-Leu-Arg-CHO), is an inhibitor of urokinase and plasmin, while leupeptin inhibits only plasmin. Pyr-Leu-Arg-CHO was shown to inhibit in vitro invasion of human fibrosarcoma HT1080 cells reducing cellular collagenase activity. Pyr-Leu-Arg-CHO suppressed the invasion of the cells in a Boyden chamber assay with an IC50 of 12 micrograms/ml. Addition of plasminogen to HT1080 cells increased the type IV collagenase activity, and Pyr-Leu-Arg-CHO inhibited this activation of the collagenase with an IC50 of 3 micrograms/ml. Leupeptin inhibited both the invasion and collagenase activation at higher concentrations than that of Pyr-Leu-Arg-CHO. The gelatin zymography of the conditioned medium revealed that a new gelatinolytic band, possibly an activated form of MMP-2, appeared by the addition of plasminogen. The activation of MMP-2 was also inhibited strongly by Pyr-Leu-Arg-CHO. These results indicate that Pyr-Leu-Arg-CHO suppresses the in vitro invasion by preventing the activation of type IV collagenase through inhibition of the urokinase-plasmin system.
...
PMID:Suppression of in vitro invasion of human fibrosarcoma cells by a leupeptin analogue inhibiting the urokinase-plasmin system. 772 42


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

---