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)

A spontaneous mammary adenocarcinoma (AC) from an inbred female rat was investigated with regard to secretion of neutral proteases. Cultures of neoplastic epithelial cells derived from the tumour secreted an enzyme that fulfilled the criteria for a specific collagenase. In contrast to cultures of non-neoplastic cells, tumour collagenase was present as an active enzyme, since treatment with trypsin or p-aminophenylmercuric acetate (APMA) did not increase activity. The neoplastic cells were also prolific producers of plasminogen activator (PA). Dexamethasone (Dex) (10(-6)M) markedly reduced the levels of both enzymes. Addition of tranexamic acid (TA), an inhibitor of plasmin and of plasminogen activation, did not affect collagenase activity, even at 10(-1)M TA, nor did latent collagenase accumulate. Latent collagenase was secreted in culture by normal fibroblasts from neonatal rat lungs. This latent enzyme was activated by the addition of tumour cell medium plus plasminogen, but this effect was inhibited by the addition of TA. These results demonstrate that the neoplastic cells themselves secrete collagenase as an active enzyme. PA is also secreted, is not involved with tumour collagenase, but is capable, in the presence of plasminogen, of activating latent collagenase produced by the non-neoplastic cells within the tumour or in the surrounding tissue. This tumour possesses potent collagenolytic ability in vitro which may be partly responsible for its rapid invasion in vivo.
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PMID:Rat mammary carcinoma cells secrete active collagenase and activate latent enzyme in the stroma via plasminogen activator. 627 36

We studied the effects of two retinoids, naturally occurring all-trans-retinoic acid (retinoic acid) and the synthetic 4-hydroxyphenylretinamide (4-OH-PRT) on monolayer cultures of rabbit synovial fibroblasts and on explants of rabbit articular cartilage. Treatment of fibroblasts with phorbol myristate acetate (PMA; 10(-8) M) induced the synthesis and secretion of large amounts of collagenase: this was inhibited if the cells were treated with retinoic acid (10(-6) M) or dexamethasone (10(-7 M). Combined treatment with retinoic acid and the steroid prednisolone, at concentrations as low as 19(-10) M, gave an additive inhibition of collagenase production. Both retinoids inhibited collagenase production, but only 4-OH-PRT prevented the increase in prostaglandin E2 (PGE2) induced by PMA. Levels of plasminogen activator were also increased by treatment with PMA, and concomitant addition of either retinoid further enhanced this stimulation. Possible toxicity was assessed by measuring release of glycosaminoglycans (GAG) from explants of articular cartilage. Treatment with retinoic acid induced release of 80% of the total GAG, whereas treatment with 4-OH-PRT resulted in release of 40% of the total, a finding similar to that seen with untreated samples. 4-OH-PRT inhibited production of collagenase and PGE2 by rabbit synovial fibroblasts but was not toxic to articular cartilage.
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PMID:Effects of all-trans-retinoic acid (retinoic acid) and 4-hydroxyphenylretinamide on synovial cells and articular cartilage. 627 10

The proteolytic activity in homogenates and extracts of subcellular fractions prepared from subcutaneous Lewis lung carcinoma was determined using proteins and synthetic peptides as substrates. The presence of cathepsin D, plasminogen activator, cathepsin B-, cathepsin G- and elastase-like enzymes was observed. No difference was revealed between the proteolytic activity in homogenates of Lewis lung carcinoma, at the growth stage examined, and in homogenates of normal lung. High specific activities were found in the lysosomal extract, whereas decreasing activities were found in the nuclear extract, the homogenate and the postlysosomal mitochondrial supernatant; no active or trypsin-activatable collagenase activity was detected. The presence in the tumor tissue of these enzymatic activities is in agreement with their proposed role in the process of metastasis. The lack of differences between homogenates of tumor and normal lung tissue suggests that the use of whole cells is required to selectively study tumor proteinases specifically involved in tumor malignancy.
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PMID:Methodologic problems encountered in the assay of proteinases in Lewis lung carcinoma, a mouse metastasizing tumor. 629 35

The relationship of a basement membrane collagen degrading enzyme (BM collagenase) and plasminogen activator (PA) was studied in a number of non-malignant and malignant human and murine cell lines. Several non-malignant cell lines secreted significant amounts of PA but not detectable BM collagenase activity whereas the malignant cell lines, with one exception, secreted both enzymes. Therefore, the secretion of BM collagenase appears to be a characteristic of many malignant cells whereas PA is synthesized also by normal cells. The BM collagenase needed proteolytic activation for maximal activity indicating that it is secreted in a latent form. The addition of plasminogen to the culture medium of human fibrosarcoma cells (HT-1080) resulted in maximal activation of the enzyme. Plasmin, but not plasminogen, increased the activity of partially purified enzyme protein. Accordingly, the activation of latent BM collagenase in vivo may be facilitated by PA through the conversion of plasminogen to plasmin. It is suggested that the secretion of BM collagenase concomitantly with PA is a prerequisite for metastasis.
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PMID:Secretion of basement membrane collagen degrading enzyme and plasminogen activator by transformed cells--role in metastasis. 629 70

Independent studies have previously shown that mononuclear cell supernatants stimulate the release of plasminogen activator and latent collagenase from synovial cell monolayer cultures. Simultaneous secretion of these enzymes could be an important pathway for tissue destruction under inflammatory conditions, since plasminogen activator can cause activation of latent collagenase in the presence of plasminogen. We investigated the kinetics of release of the two enzymes from synovial cells in response to the addition of mononuclear cell supernatants and retinoic acid. Synovial cells derived from osteoarthritic and rheumatoid arthritic patients responded similarly. Plasminogen activator is released within a few hours of stimulation, and secretion usually stops when the stimulus is removed. In contrast, significant amounts of collagenase are secreted only after an initial lag period of 1--2 days, and secretion is sustained long after removal of mononuclear cell supernatant. Another difference in regulation of the secretion of these two neutral proteinases is that the addition of all-trans retinoic acid to the same synovial cell culture elevates plasminogen activator secretion while suppressing that of latent collagenase. Differential regulation of these enzymes under conditions of chronic inflammation may allow for continual accumulation of latent enzyme(s) which are activated during short periods of plasminogen activator release.
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PMID:Differential release of plasminogen activator and latent collagenase from mononuclear cell-stimulated synovial cells. 629 7

Dispersed cells from human amnion and chorion were cultured with and without relaxin. The addition of this hormone caused an increased secretion of both collagenase and plasminogen activator into the culture medium over a 32 h period, but had no effect on proteoglycanase or beta-glucuronidase secretion. The increase in plasminogen activator was dose-related to the amount of relaxin added in vitro. The results show that the fetal membranes are a novel target tissue for relaxin in the human, and suggest that relaxin in vivo may cause a similar release of collagenolytic enzymes, leading to the weakening and eventual rupture of the fetal membranes.
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PMID:Relaxin stimulates collagenase and plasminogen activator secretion by dispersed human amnion and chorion cells in vitro. 630 28

Bovine capillary endothelial (BCE) cells produce increased amounts of the proteases plasminogen activator (PA) and latent collagenase when cultured in the presence of the following preparations which are known to contain angiogenic activities: bovine retinal extract, mouse adipocyte conditioned medium, and human hepatoma cell lysate. These preparations stimulated both BCE cell PA and collagenase activities in a dose-dependent manner. Both activities were increased to about the same level by these preparations as by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate. Mitogens that are not angiogenic, such as insulin, epidermal and fibroblast growth factors, and endothelial cell growth supplement, had no effect on BCE cell PA and collagenase activities. Two of the angiogenic preparations (retinal extract and mouse adipocyte-conditioned medium) had no effect on PA activity in endothelial cells derived from bovine aortae (BAE cells). The angiogenic preparations had little (human hepatoma cell lysate, mouse adipocyte-conditioned medium) or no (bovine retinal extract) effect on BAE cell collagenase activities. In the bovine system, the induction of high levels of both PA and collagenase activities by angiogenic preparations is limited to capillary endothelial cells.
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PMID:Increased capillary endothelial cell protease activity in response to angiogenic stimuli in vitro. 630 97

Hydrolytic enzymes are major constituents of alveolar macrophages, which in recent years have been shown to be involved in many aspects of the inflammatory response in addition to their better-known role in bactericidal processes. This review summarizes the general properties, physiologic function, cellular physiology, and clinical associations of four important hydrolytic enzymes of alveolar macrophages--lysozyme, elastase, plasminogen activator, and collagenase--with particular attention to the relationship of these enzymes to the pathophysiology of lung disease. The information reviewed shows that much is known about the biochemistry of these enzymes, that each is produced in greater quantity when alveolar macrophages are stimulated, that each has a distinctive physiologic role in the inflammatory process, and that they function as part of the overall pulmonary antibacterial defense system. Studies of the pathophysiologic effects consequent to the elaboration of excess quantities of these enzymes by stimulated macrophages show that some hydrolytic enzymes injure the lung by attacking normal as well as inflammatory tissue sites that are susceptible to degradation. Such damage is normally limited by enzymatic inhibitors, like alpha-antitrypsin, but the inactivating capacity of the inhibitors can be overwhelmed and in these instances excess enzyme contributes to the development of emphysema. This newer understanding of the pathophysiologic role of hydrolytic enzymes may lead to therapeutically beneficial methods for modulating the pulmonary inflammatory response.
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PMID:Hydrolytic enzymes of alveolar macrophages. 631 90

Human synovial fluid often contains small cartilaginous "wear particles." Previous in vitro experiments have indicated the potential involvement of these particles in the pathophysiology of arthritis. To determine whether this potential is realized under the conditions existing within joints, standard suspensions of lapine articular cartilage were injected intraarticularly into the knee joints of rabbits. Thrice-weekly injections of 1 mg allogenic cartilage produced an inflammatory arthritis, accompanied by a marked cellular effusion, in all rabbits within 5 months. The synovium became hyperplastic, discolored, and infiltrated with mononuclear inflammatory cells. Embedded particles of the injected material were seen in histologic preparations of these synovia. Organ cultures of such synovia produced 4 to 5 times more collagenase, plasminogen activator, "Pz-peptidase," neutral and acid azocaseinase, and beta-glucuronidase than did cultures of synovia from control knees injected with saline. Furthermore, the articular cartilage of knees injected with cartilaginous particles showed elevated intrinsic collagenolytic activity. Histologic examination of the articular cartilage revealed an attendant loss of metachromasy, resulting in friability, pitting, and discoloring of the cartilage. Preliminary immunoassays failed to demonstrate a systemic immune response to the injected material.
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PMID:Experimental arthritis induced by intraarticular injection of allogenic cartilaginous particles into rabbit knees. 632 Aug 35

Several angiogenic preparations that have been shown to stimulate plasminogen activator (PA) and collagenase production by cultured bovine capillary endothelial (BCE) cells were tested for their ability to stimulate BCE cell motility in the phagokinetic track assay. Bovine retinal extract, medium conditioned by 3T3-F442A differentiated mouse adipocytes, SK HEP-1 human hepatoma cell lysate, mouse sarcoma 180 cell lysate, and medium conditioned by mouse sarcoma 180 cells stimulated motility 68.7%, 48.5%, 140.9%, 56.5%, and 102.1%, respectively, relative to untreated cells. The motility-stimulating activity of these preparations was dose dependent and linear over the 16-h assay period. Several hormones and growth factors were tested for BCE cell motility-stimulating activity, including insulin, vasopressin, fibroblast growth factor, and a partially purified preparation of sarcoma growth factor, and were found to be ineffective. 12-0-tetradecanoyl-phorbol-acetate (TPA), a potent stimulator of both PA and collagenase activities in BCE cells, also did not stimulate motility, indicating that protease production is not sufficient to stimulate BCE cell motility in this assay. Neither SK HEP-1 hepatoma cell lysate nor TPA was effective in stimulating motility in bovine aortic endothelial (BAE) cells. The inability of SK HEP-1 hepatoma cell lysate to stimulate movement in BAE cells is consistent with the observation that angiogenesis occurs by sprouting of capillaries, not large vessels.
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PMID:Stimulation of motility in cultured bovine capillary endothelial cells by angiogenic preparations. 632 76


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