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:3.4.21.7 (plasmin)
9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monolayer cultures of human epithelial and endothelial cells were used to study the association of latent transforming growth factor-beta 1 (TGF-beta 1) to extracellular matrices and its release and activation during matrix degradation. Human umbilical vein endothelial cells and embryonic lung fibroblasts produced relatively high levels of TGF-beta 1, its propeptide (beta 1-latency-associated protein), and latent TGF-beta-binding protein and incorporated latent TGF-beta 1 into their matrices as shown by immunoblotting. Amnion epithelial cells produced lower levels of these proteins. Confluent cultures of epithelial cells were exposed to matrix-degrading proteases and glycosidases. Mast cell chymase, leukocyte elastase, and plasmin efficiently released matrix-bound latent TGF-beta 1 complexes, while chondroitinase ABC and heparitinases were ineffective. The ability of the proteases to activate recombinant latent TGF-beta 1 was tested using growth inhibition assays and a novel sodium deoxycholate-polyacrylamide gel electrophoresis followed by immunoblotting. Sodium deoxycholate solubilized M(r) 25,000 TGF-beta 1 but did not dissociate high M(r) latent TGF-beta 1 complexes, allowing separation of these forms by polyacrylamide gel electrophoresis. Mast cell chymase and leukocyte elastase did not activate latent TGF-beta 1, suggesting that its release from matrix and activation are controlled by different mechanisms. The release of TGF-beta from the matrix by leukocyte and mast cell enzymes may contribute to the accumulation of connective tissue in inflammation.
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PMID:Human mast cell chymase and leukocyte elastase release latent transforming growth factor-beta 1 from the extracellular matrix of cultured human epithelial and endothelial cells. 787 40

We have previously demonstrated that thrombin possesses an active yet cryptic Arg-Gly-Asp (RGD) site which upon exposure induces endothelial cell (EC) adhesion via alpha nu beta 3 integrin [Bar-Shavit et al. (1991): J Cell Biol 112:335]. This was achieved in the presence of cell surface-associated heparan sulfate proteoglycans (HSPG) and exceedingly low concentrations of plasmin [Bar-Shavit et al. (1993): J Cell Biol 123:1279]. A portion of the cell surface-associated HSPG (glypican) is anchored via a covalently linked glycosyl-phosphatidylinositol (PI) residue, which can be released by treatment with glycosyl-PI-specific phospholipase C (PI-PLC). We report here that exposure of either bovine aortic EC, smooth muscle cells (SMC), or wild-type CHO cells to PI-PLC released HSPG involved in the conversion of thrombin to an adhesive molecule. The adhesion-promoting activity of the released HSPG was abolished following treatment with heparinase but not chondroitinase ABC. Incubation of thrombin with heparan sulfate-deficient CHO cells or cells that were pretreated with PI-PLC failed to induce its conversion to an adhesive molecule, indicating that glypican was playing a major role in this conversion. Moreover, affinity-purified glypican, but not syndecan or fibroglycan, elicited efficient conversion of plasmin-treated thrombin into an adhesive molecule. Antibodies raised against the RGD site in thrombin failed to interact with native thrombin, prothrombin, or the RGD site in other adhesive proteins such as vitronectin, fibrinogen, or fibronectin. Anti-thrombin-RGD antibodies which blocked the adhesion-promoting activity of thrombin were also capable of recognizing thrombin that was first incubated with a suboptimal concentration of plasm in in the presence of PI-PLC-released HSPG. Heparin, heparan sulfate, and PI-PLC-released HSPG had no effect on other cellular properties of thrombin such as receptor binding and growth-promoting activity. Altogether we have demonstrated that the heparin binding domain in thrombin plays a specific role in promoting thrombin adhesive properties and that membrane-associated glypican is likely to be the major physiological inducer of this property.
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PMID:Specific involvement of glypican in thrombin adhesive properties. 917 91

The complex molecular and cellular processes of metastatic invasion as well as the anti-invasion possibilities are summarized. Invasion by neoplastic cells is a major obstacle to successful cancer therapy. Enzymes such as hyaluronidase, sialyltransferase, urokinase-type plasminogen activator, plasmin, matrix metalloproteinases, and others, play central roles in the catabolism of extracellular matrix macromolecules. However, this process can be opposed by inhibitors of these enzymes. Both invasion (promoters) and anti-invasion factors (suppressors) need further investigation, to clarify the role of these factors in the aetiology and possibly in the treatment and prognosis of metastatic cancer.
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PMID:A possible role for enzymes in tumour-cell invasion. 918 34

Transforming growth factor-beta (TGF-beta) is normally secreted in a latent form, and plasmin-mediated proteolytic cleavage of latency-associated peptide (LAP), a component of latent TGF-beta complex that makes the complex inactive, activates latent TGF-beta. In the present study, we investigated the possible involvement of calpain, one of the cysteine proteases, in the activation of latent TGF-beta. When recombinant latent TGF-beta was incubated with calpain (1-10 u/ml) in a test tube, calpain cleaved LAP and released mature TGF-beta from the latent complex. When calpain was applied to cultured bovine capillary endothelial (BCE) cells, a low concentration of calpain (0.05-0.1 u/ml) inhibited the migration and proliferation of the cells, and these inhibitory effects were abrogated by anti-TGF-beta antibody as well as by calpain inhibitor peptide, but not by alpha2-antiplasmin, a specific inhibitor of plasmin. Active TGF-beta was detected in the conditioned medium of BCE cells collected in the presence of calpain. Chemical cross-linking of (125)I-calpain to BCE cells followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis indicated that calpain bound to the cell surface through chondroitinase ABC-sensitive proteoglycan. In addition, treatment of the BCE cells with chondroitinase ABC abrogated the inhibitory effect of calpain on the migration of these cells. Our data thus suggest that calpain is able to activate latent TGF-beta through a mechanism independent of plasmin. This activation is efficient in the presence of cells, and calpain binds to the cell surface via proteoglycan and activates latent TGF-beta, which is targeted to the same surface.
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PMID:Cell-associated activation of latent transforming growth factor-beta by calpain. 942 5

Mastitis caused by environmental pathogens is a major problem that affects many well-managed dairy herds. Among the environmental pathogens, Streptococcus dysgalactiae is isolated frequently from intramammary infections during lactation and during the nonlactating period. In spite of its high prevalence, little is known about factors that contribute to the virulence of S. dysgalactiae. During the last decade, several cell-associated and extracellular factors of S. dysgalactiae have been identified; yet, the relative importance of these factors in the transmission and pathogenesis of mastitis caused by S. dysgalactiae has not been defined. Streptococcus dysgalactiae can interact with several plasma and extracellular host-derived proteins such as immunoglobulin G, albumin, fibronectin, fibrinogen, collagen, vitronectin, plasminogen, and alpha 2-macroglobulin. These interactions are mediated by bacterial surface proteins. This organism also produces hyaluronidase and fibrinolysin which may be involved in promoting dissemination of the organism into host tissue. Streptococcus dysgalactiae adheres to and is internalized by bovine mammary epithelial cells in vitro. Involvement of host cell kinases, intact microfilaments and de novo eukaryotic protein synthesis are required for internalization of S. dysgalactiae into bovine mammary epithelial cells; a process that appeared to occur by a receptor-mediated endocytosis mechanism. However, de novo bacterial protein synthesis was not required for epithelial cell internalization. Furthermore, S. dysgalactiae survived within mammary epithelial cells for extended periods of time without losing viability or damaging the eukaryotic cell. Further research on characterization of host-pathogen interactions that take place during the early stages of mammary gland infection will enhance our understanding of pathogenesis of intramammary infection which may contribute to development of methods to minimize production losses due to mastitis.
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PMID:Potential virulence factors of Streptococcus dysgalactiae associated with bovine mastitis. 964 69

Pharmacological vitrectomy refers to the use of enzymes in an effort to liquefy vitreous and to weaken the adhesion of vitreous cortex to the internal limiting membrane during or before performing vitreous surgery. It is well known that the vitreoretinal interface plays important roles in developing many blinding diseases. To make the vitreous surgery easier for better outcome or to avoid vitrectomy, plasmin, dispase, and chondroinase have been used to promote the disinsersion of vitreous cortex to the internal limiting membrane, a basement membrane of Muller cells. On the other hand, hyaluronidase has been used clinically to facilitate the clearance of vitreous hemorrhage liquefying vitreous body and developing posterior vitreous detachment. This article reviews enzymes as an intraoperative adjunctive agent in vitrectomy.
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PMID:Pharmacological vitrectomy. 1074 15

The first investigations to treat diseases of the posterior segment enzymatically started 40 years ago. To treat acute subretinal hemorrhage a pneumatic displacement through intravitreally injected gas after enzymatically induced subretinal fibrinolysis (TPA) is recommended. Recent morphometric analysis clearly demonstrated a subretinal fibrinolytic effect after intravitreal injection of TPA. Obviously TPA crosses the retina through microlesions that develop through elevation of the retina during acute bleeding. For the first time pars plana vitrectomy was superseded by a simple and gentle enzymatic therapy combined with pneumatic displacement by intravitreally injected gas. Increasing experience with pars plana vitrectomy demonstrated that a complete removal of the vitreous body has beneficial effects on the course of vasoproliferative vitreoretinal diseases. Therefore enzymes were tested to either liquefy the vitreous body (collagenase or hyaluronidase) or to cleave the posterior vitreous cortex and the retina (dispase, plasmin, tissue plasminogen-activator or chondroitinase). At present only tissue-plasminogen activator (TPA), plasmin and hyaluronidase were used in small clinical studies. Recent developments in the understanding of vasoproliferative vitreoretinal disorders offers new therapeutical approaches like enzymatical destruction of growth factors (VEGF) or extracellular adhesive proteins (fibronectin). From this point of view future therapies may include enzymatic cleaning of the vitreous body to prevent proliferative diabetic vitreoretinopathy.
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PMID:[Using enzymes in the posterior eye segment. Current status and future possibilities]. 1179 1

The aim of using enzymes in vitreoretinal surgery is to facility PVD and create pharmacological vitrectomy. It can be achieved by liquefying the gel structure of the vitreous (synchisis) and weakening of adherence of the posterior vitreous cortex to retina (syneresis). The article reviews currently used enzymes in vitreoretinal surgery (plasmin, hyaluronidase, dispase, chondroitinase, collagenase, urokinase, TPA--tissue plasminogen activator) and presents potential profits and side-effects related to their use. Although the day when vitreous surgery is replaced by pharmacological vitreolisis remains still as a future, these enzymes hold great promise. Additionally it has been proved that enzymes can be used successfully as an intraoperative adjuvant in vitrectomy.
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PMID:[Use of enzyme in vitreoretinal surgery]. 1204 13

This assay employs a biotinylated heparan sulfate glycosaminoglycan (HSGAG) substrate that is covalently linked to the surface of 96-well immunoassay plates. The ratio of biotin:HSGAG and the coating concentration of substrate bound to the wells have been optimized and allow removal of biotin HSGAG within 60 min of incubation at 37 degrees C in assay buffer with a standard dilution of bacterial heparitinase or platelet heparanase. Loss of biotin signal from the well surface is detected on incubation with peroxidase-streptavidin followed by color development using 3,3',5,5'-tetramethylbenzidine as the peroxidase substrate. The new assay allows specific detection of heparanase activity in multiple samples in a total time of 3 h including a 1-h substrate digestion step and is a significant improvement with regard to sensitivity, specificity, and ease of handling of multiple samples compared to other described assays. Heparanase specifically degrades the biotinylated HSGAG substrate, when used with an optimized assay buffer. A range of enzymes including collagenase, trypsin, plasmin, pepsin, chondroitinases, hyaluronidase, and neuraminidase show no effect on the substrate under optimized assay conditions. The covalent linkage of the substrate to the well prevents leaching of substrate and allows preparation and long-term storage of substrate-coated plates. The assay can be used to detect heparanase levels in clinical samples and cell culture supernatants and is ideal as a screening method for antagonists of enzyme activity.
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PMID:A multiwell format assay for heparanase. 1292 26

Heterotrophic plate counts (HPCs) are commonly used to assess the general microbiological quality of drinking water. Drinking water quality specifications worldwide recommend HPC limits from 100 to 500 cfu ml(-1). A number of recent studies revealed evidence that these bacteria may not be as harmless as generally accepted. It appears that immuno-compromised individuals are particularly at risk. This would include the very young and very old patients with diseases such as AIDS and patients on therapy for purposes such as organ transplantation and cancer treatment. In this study, 339 bacterial colonies were isolated at random from selected treated and untreated drinking water in South Africa using routine heterotrophic plate count tests. In a first step to screen for potentially pathogenic properties, 188 (55.5%) of the isolates showed alpha- or beta-haemolysis on human- and horse-blood agar media. Subsequent analysis of the haemolytic isolates for enzymatic properties associated with pathogenicity revealed the presence of chondroitinase in 5.3% of the isolates, coagulase in 16.0%, DNase in 60.6%, elastase in 33.0%, fibrinolysin in 53.7%, gelatinase in 62.2%, hyaluronidase in 21.3%, lecithinase in 47.9%, lipase in 54.8% and proteinase in 64.4%. Fluorescein and pyocyanin were not produced by any of the isolates. Among the haemolytic isolates, 77.7% were resistant to oxacillin 1 microg, 59.6% to penicillin G 2 units, 47.3% to penicillin G 10 units, 54.3% to ampicillin 10 microg and 43.1% to ampicillin 25 microg. Cell culture studies revealed that 96% of haemolytic isolates were cytotoxic to HEp-2 cells, and 98.9% of the 181 cytotoxic isolates adhered to HEp-2 or Caco-2 cells. HEp-2 cells were invaded by 43.6%, and Caco-2 cells by 49.7%, of the 181 cytotoxic isolates. The invasion index on HEp-2 cells ranged from 1.9 x 10(-1) to 8.9 x 10(-6), whereas the invasion index on Caco-2 cells varied between 7.7 x 10(-2) and 8.3 x 10(-6). The most commonly isolated genera with these potentially pathogenic features were Aeromonas, Acinetobacter, Aureobacterium, Bacillus, Chryseobacterium, Corynebacterium, Klebsiella, Moraxella, Pseudomonas, Staphylococcus, Tsukamurella and Vibrio. The results obtained in this study support earlier findings on potentially pathogenic features of bacteria detected by routine HPCs on drinking water. These findings are in agreement with some epidemiological studies, which indicated an association between HPCs in drinking water and the incidence of gastroenteritis in consumers. However, the extent of the health risk concerned needs to be defined in more detail for meaningful revision of quality guidelines for HPCs in drinking water.
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PMID:Potentially pathogenic features of heterotrophic plate count bacteria isolated from treated and untreated drinking water. 1514 86


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