Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-1 (IL-1) is the name given to a family of related proteins showing a variety of activities. It was originally shown to be produced by monocytes and macrophages but is now known to be produced by numerous cell types, including synovial cells. From the point of view of arthritis, its most interesting activities are those on connective tissue cells in vitro. These include stimulation of production of prostaglandins, plasminogen activator and metalloproteinases such as collagenase and proteoglycanase. IL-1 is also mitogenic for synoviocytes and bone cells, and can alter rates of production of extracellular matrix constituents. The presence of IL-1 in synovial fluids from rheumatoid and osteoarthritic joints and its actions on connective tissues in vitro suggest that IL-1 may play an important role in the pathogenesis of arthritis. There are several potential cellular sources of IL-1 in the inflamed rheumatoid joint and interactions between these cells, T lymphocytes and plasma cells may continually induce IL-1 so contributing to the chronicity of the disease. The mechanism of action of IL-1 on connective tissue cells is at present uncertain though preliminary studies suggest that IL-1 may induce cellular responses by stimulating phosphoinositide turnover and possibly protein kinase C activity.
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PMID:The effect of interleukin-1 on connective tissue metabolism and its relevance to arthritis. 352 46

Neutrophil elastase digests plasminogen to yield a fragment, mini-plasminogen, which is activatable to a mini-plasmin capable of escaping the action of the primary plasmin inhibitor. Such a molecule may play a role in joint destruction, either directly or by activation of procollagenase to collagenase. Synovial fluid samples from 34 acute joint effusions were examined by lysine-Sepharose chromatography and fibrinolytic assay of the fall-through (non-lysine-binding) fractions in presence of urokinase. Fragments similar to mini-plasminogen were found in 20 of 23 inflammatory effusions (cell count greater than 0.5 X 10(3)/microliter) and in none of 11 non-inflammatory (traumatic and osteoarthritic) effusions (cell count less than 0.5 X 10(3)/microliter) (p less than 0.001). Analysis of four inflammatory fluids by gel filtration on Bio-Gel P 100 and enzyme-linked immunoassay for plasminogen antigen revealed plasminogen fragments with molecular weight similar to mini-plasminogen (34,000 daltons) in three, and larger plasminogen fragments (or complexes of mini-plasminogen with other synovial fluid macromolecules) in all four. Fibrinolytic activity was demonstrable in fractions containing plasminogen fragments after treatment with tissue type plasminogen activator. In contrast with non-inflammatory effusions, inflammatory joint fluids contain plasminogen fragments with the properties of mini-plasminogen, suggesting their possible role in inflammatory joint destruction.
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PMID:Mini-plasminogen-like fragments of plasminogen in synovial fluid in acute inflammatory arthritis. 363 68

Activities of several proteinase-like peptidases have been determined in homogenates of malignant tissue, non-malignant tissue adjacent to the tumour (A-NM) and non-malignant tissue distant to the tumour (D-NM) from 17 patients undergoing surgery for histologically confirmed gastric malignancies. In homogenates of malignant tissues the activities of collagenase, cathepsin B, cathepsin (B+L), cathepsin H and cathepsin D were significantly higher than in D-NM tissues. By contrast, the levels of plasminogen activator were significantly lower in malignant tissues than in the D-NM tissues. Furthermore, the activities of collagenase-like and the cysteine-proteinase-like peptidases in the A-NM tissues were lower than in malignant tissues but higher than in the D-NM tissues. Separation of full-thickness non-malignant tissues into mucosal and seromuscular layers revealed significantly higher activities in the former. The elevated levels of these proteinase-like peptidases in homogenates of gastric cancer tissue suggests an important role for these enzymes in tumour invasion.
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PMID:Proteinase-like peptidase activities in malignant and non-malignant gastric tissue. 388 38

Relaxin (Rlx) is shown in vitro to increase the release of plasminogen activator (PA) activity from granulosa cells obtained from 28-day-old rats after priming 48 h before with PMSG. Priming with PMSG was essential for the subsequent marked increase in PA by the addition of Rlx to these cells in vitro. Under the same conditions Rlx also increased the release of both total collagenase and total proteoglycanase activities but not of beta-glucuronidase activity. The total collagenase and proteoglycanase activities of control cells are made up of essentially equal amounts of their respective active and latent enzymes. Rlx stimulation increases the amounts of the respective active enzymes while the latent collagenase and proteoglycanase activities are unchanged or decreased, respectively. The enzyme beta-glucuronidase was not stimulated by Rlx and appears not to be involved in follicular proteoglycan degradation. Granulosa cells harvested from preantral follicles responded most to FSH by PA production whereas cells from antral follicles responded more to LH, reflecting the known changes in concentration of FSH and LH receptors on these cells. The release of PA is maximal by all four hormones studied (FSH, LH, prostaglandin E1, and Rlx) on granulosa cells harvested from rats 48 h after PMSG treatment and this suggests that the follicles at this time are a mixture of both preantral and antral stages. The PA response to FSH is lost by 60 h after PMSG at the same time that the response to prostaglandin E1 is maintained at the same level, whereas that to Rlx and LH, although still significantly higher than controls, were decreased. By 70 h after PMSG, postovulatory, the responses to all hormones studied were lost. Thus, the involvement of PA in ovarian connective tissue alterations appears to be greatest in the period of follicular antrum formation rather than just before ovulation. Rlx is one of a number of hormones involved in the sequence of events culminating in follicle connective tissue remodeling as shown by its action on the release of three intrafollicular enzymes.
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PMID:Relaxin increases the release of plasminogen activator, collagenase, and proteoglycanase from rat granulosa cells in vitro. 608 81

Eighteen clones of a methylcholanthrene-induced murine fibrosarcoma (3AM) which were heterogeneous with respect to metastatic potentials and in vivo growth rates were examined for five different protease activities: acid protease (cathepsin D), BANA hydrolase (cathepsin B), neutral protease, collagenase, and plasminogen activator. Homogenates of the solid tumors produced by the clones were heterogeneous with respect to the activities of the proteases; these activities were in all cases (except plasminogen activator) higher than those obtained for normal muscle tissue. There was, however, no correlation between any of these protease activities and the metastatic potential or in vivo growth rates. The cathepsin B activity has also been evaluated on the cultured cells of the various clones. Results similar to that of the in vivo study were obtained. Analysis of the enzyme activity of the cell culture and of organ culture media, however, revealed no cathepsin B activity. It is concluded that the measurement of any one biochemical parameter such as proteolysis may not be sufficient to establish a correlation with the overall process of metastasis; a more precise dissection of the individual steps culminating in metastasis may provide a more fruitful approach to this problem.
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PMID:Proteolytic and metastatic activities of clones derived from a methylcholanthrene-induced murine fibrosarcoma. 610 Aug 5

Bovine capillary endothelial cells have been found to respond to several stimuli by producing increased amounts of plasminogen activator and latent collagenase. These stimulators include the tumor promoter tetradecanoyl phorbol-13-acetate as well as crude preparations from a human hepatoma, bovine retinae, and mouse adipocytes, all of which are known to contain angiogenic factors. Endothelial cells and skin fibroblasts do not respond to these stimuli in the same way, indicating a specificity of the response. In addition, inhibitors of plasmin and vertebrate collagenase have been isolated from cartilage, a tissue resistant to neovascularization. We have proposed that these specific protease inhibitors confer on cartilage its antiangiogenic properties.
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PMID:The involvement of proteases and protease inhibitors in neovascularization. 617 34

Cultured bovine capillary endothelial (BCE) cells produce low levels of collagenolytic activity and significant amounts of the serine protease plasminogen activator (PA). When grown in the presence of nanomolar quantities of the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA), BCE cells produced 5-15 times more collagenolytic activity and 2-10 times more PA than untreated cells. The enhanced production of these enzymes was dependent on the dose of TPA used, with maximal response at 10(-7) to 10(-8) M. Phorbol didecanoate (PDD), an analog of TPA which is an active tumor promoter, also increased protease production. 4-O-methyl-TPA and 4alpha-PDD, two analogs of TPA which are inactive as tumor promoters, had no effect on protease production. Increased PA and collagenase activities were detected within 7.5 and 19 h, respectively, after the addition of TPA. The TPA-stimulated BCE cells synthesized a urokinase-type PA and a typical vertebrate collagenase. BCE cells were compared with bovine aortic endothelial (BAE) cells and bovine embryonic skin (BES) fibroblasts with respect to their production of protease in response to TPA. Under normal growth conditions, low levels of collagenolyic activity were detected in the culture fluids from BCE, BAE, and BES cells. BCE cells produced 5-13 times the basal levels of collagenolytic activity in response to TPA, whereas BAE cells and BES fibroblasts showed a minimal response to TPA. Both BCE and BAE cells exhibited relatively high basal levels of PA, the production of which was stimulated approximately threefold by the addition of TPA. The observation that BCE cells and not BAE cells produced high levels of both PA and collagenase activities in response to TPA demonstrates a significant difference between these two types of endothelial cells and suggests that the enhanced detectable activities are a property unique to bovine capillary and microvessel and endothelial cells.
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PMID:Plasminogen activator and collagenase production by cultured capillary endothelial cells. 618 6

Although ulceration of the corneal stroma after alkali burns is known to be correlated with persistent epithelial defects, the relationship between a defect and the mediators thought to contribute to stromal destruction (plasminogen activator, plasmin, collagenase) has not been understood. This report demonstrates that fibrin and fibronectin appear on the stromal surface after an alkali burn, and that those substratum, matrix components disappear in correlation with the appearance of plasminogen activator on the stromal surface, re-surfacing by the epithelium and a persistent epithelial defect. The facts that epithelium releases plasminogen activator and that plasmin, generated from plasminogen by an activator, can degrade both fibrin and fibronectin, as well as the laminin component of the subepithelial basement membrane, would suggest that the plasminogen activator-plasmin system effect degradation of those macromolecules, thus initiating the events that lead to eventual, frank stromal ulceration. It is hypothesized that stromal ulceration is initiated by the chronic secretion from an epithelium with a persistent defect of a protease (plasminogen activator) involved in wound healing.
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PMID:Ulceration is correlated with degradation of fibrin and fibronectin at the corneal surface. 622 46

Plasminogen is present in the cornea andcan be activated to plasmin by plasminogen activator. Plasmin is able, in turn, to activate latent collagenase. This system could initiate and perpetuate the collagen degradation of corneal ulceration. This report details evidence for such a system in the cornea. Plasmin has been found to activate latent collagenase from organ cultures of ulcerating rabbit corneas and from fibroblast cultures derived from such corneas. As in the case of activation by trypsin, activation by plasmin results in the conversion of the 40,000 MW latent form to an active species of 23,000 MW. Explants of normal or alkali-burned, ulcerating corneas demonstrated plasminogen-dependent lysis of fibrin clots; frozen sections of such corneas demonstrated that lysis begins in the superficial stroma near the periphery of the cornea. Multiply freeze-thawed ulcerating corneas, but not normal corneas, showed initial lysis, not peripherally but at the ulcer region containing polymorphonuclear leukocytes. The fact that the peripheral lytic pattern existed in corneas that were obtained from eyes prefrozen in liquid nitrogen before excision of the corneas would suggest that plasminogen activator is normally contained in cells in vivo and is not made only in response to tissue injury. There was no correlation between the location of blood vessels or the presence of the corneal endothelium and the plasminogen-dependent lysis. Plasminogen activator from the ulcerating cornea and from fibroblasts was characterized by sodium dodecyl sulfate--gel electrophoresis of its cleavage products of plasminogen. The activator cleaves plasminogen into heavy- and light-chain fragments similar to those produced from plasminogen by urokinase. Plasminogen activator activity was quantitated by a new assay that restricts diffusion of the enzyme to one dimension into a narrow bore tube. The addition of plasminogen daily to cultures of ulcerating corneas resulted in earlier rises of plasminogen activator, collagenase, and collagen degradation fragments in the culture media. Although total plasminogen activator levels were not increased by the addition of plasminogen to culture, levels of both collagenase and solubilized collagen were approximately doubled. It is concluded that the plasminogen activator--plasmin system might play an important role in the destruction of stromal matrix in corneal ulceration.
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PMID:Evidence for a role of the plasminogen activator--plasmin system in corneal ulceration. 625 12

Both malignant (adenocarcinomas) and nonmalignant (fibroadenomas and normal tissue) human breast tissues were maintained in organ culture for up to 10 days to study the secretion of lysosomal and neutral proteinases. Little difference was observed between the different tissue groups in the release of the lysosomal proteinase cathepsin D into the culture medium. Similar results were obtained when media were tested for plasminogen activator activity. The secretion of collagenolytic activity was investigated with fibroadenoma and adenocarcinoma explants and found to be very low for both tissue groups. The average accumulation of collagenase activity during a 2-day period was 0.002 units/microgram DNA for adenocarcinomas and 0.008 units/microgram DNA for fibroadenomas. The only proteinase that was secreted in substantially higher amounts from explants of malignant tissue was a cathepsin B-like thiol proteinase. Media from adenocarcinoma explants (n = 38) contained on the average 11 times more activity than did media from fibroadenoma (n = 20) and normal tissue explants (n = 8). Metastases of mammary adenocarcinomas (n = 7) secreted the thiol proteinase at about one third of the rate of primary tumors. The secretion of this enzyme is dependent upon protein synthesis as its release was completely inhibited 24 hr after the addition of cycloheximide. In some cases, it was also observed that the presence of sheep serum in the tissue culture medium reduced the accumulation of activity.
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PMID:Secretion of proteinases from malignant and nonmalignant human breast tissue. 625 82


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