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)

The effect of therapeutic and pharmacological concentrations of tiaprofenic acid, a non-steroidal anti-inflammatory drug (NSAID), on the synthesis of the plasminogen activators, urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA), and the plasminogen activator inhibitors 1 and 2 (PAI-1 and PAI-2), by human synovial membranes isolated from osteoarthritis (OA) and rheumatoid arthritis (RA) sufferers was evaluated. Both forms of plasminogen activator (PA) and PA inhibitor (PAI) were synthesized by the arthritic synovium. PAI-1 and PAI-2 were both synthesized in greater amounts than the plasminogen activators. Tiaprofenic acid induced a dose-dependent decrease in uPA synthesis in both OA and RA, particularly in OA synovium, but had no true effect on tPA. Tiaprofenic acid also exerted a suppressive effect on the synthesis of PAI-1 in both OA and RA synovial membranes, and on the release of PAI-2 in RA synovium. The results of this study indicate that a decrease in uPA synthesis may be one of the mechanisms by which tiaprofenic acid could exert its effects on the arthritic process. The suppressive action of tiaprofenic acid on PAI is not likely to have a significant impact on the balance of plasminogen activators and plasminogen activator inhibitors, as plasminogen activator inhibitors are synthesized in greater amounts than plasminogen activators.
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PMID:Effects of tiaprofenic acid on plasminogen activators and inhibitors in human OA and RA synovium. 155 50

Osteoarthritis (OA) is characterized by a progressive erosion of cartilage, which is mediated by the protease degradation of the extracellular matrix components. Plasmin, plasminogen activators (PA) and the inhibitor of plasminogen activator (PAI) are thought to play an important role in the regulation of the OA pathophysiology process. Our study determined the activity of plasmin and PA in OA and normal cartilage. Moreover, the presence and the content of each form of PA, uPA and tPA, as well as the inhibitor PAI-1, were determined using immunohistological techniques and ELISA. Our studies were carried out on fresh cartilage, cultured tissue explants and chondrocytes. OA cartilage demonstrates about 5 times more plasmin activity than the controls (p less than 0.001). Moreover, a statistically significant correlation was found between the plasmin activity and the free collagenolytic form in OA specimens showing severe lesions (r = 0.50; p less than 0.05). Our study revealed that PA content and activity increase in OA cartilage following culture explant experiments. Immunohistochemical studies showed the presence of both uPA and tPA forms in OA cartilage lesions only. Protein determinations revealed uPA as the predominant form. PAI-1 was significantly decreased (p less than 0.04) in OA, and was located mainly extracellularly. Chondrocyte cultures showed the ability to synthesize both forms of PA and PAI-1. Our study demonstrated an increased level of plasmin activity in OA cartilage. This is likely related to increased PA activity, in which the urokinase type appeared to be predominant in OA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasmin, plasminogen activators and inhibitor in human osteoarthritic cartilage. 172 64

The effects of tranexamic acid, an inhibitor of plasminogen activator, were evaluated in a rabbit model of osteoarthritis induced by section of the knee joint anterior cruciate ligament. Prophylactic treatment administered intramuscularly thrice weekly for 12 or 24 weeks significantly reduced cartilage destructive lesions, increased cartilage hypertrophy but did not prevent changes in cartilage water and proteoglycan content. A suppression of synovial membrane stromelysin and collagenase activity was found while phospholipase A2 activity was unaffected.
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PMID:Study of an inhibitor of plasminogen activator (tranexamic acid) in the treatment of experimental osteoarthritis. 185 Dec 28

The fibrinolytic activity (FA) has been studied on the synovial membrane obtained from 16 patients with osteoarthritis (OA), 20 patients with rheumatoid arthritis (RA) and 11 control subjects. Todd's autohistographic method, modified by Lotti, was used to investigate the FA and the monoclonal antibodies against u-PA and t-PA were used to identify the main plasminogen activator. Our results show that the FA is increased in the synovial membrane of patients with OA in comparison with the synovial FA of control subjects. In the synovial membranes from patients with RA, the FA shows different results: in some specimens FA is increased, and in others it is diminished or similar, compared with FA of samples from healthy controls. Thus, our data on synovial FA in OA confirm the previous reports, performed in vitro, on the activation of the plasmin system in this degenerative disease. The activity of the fibrinolytic system seems to participate in the cartilage degeneration and, via the activation of collagenase, to perpetuate the cartilage damage.
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PMID:Fibrinolytic activity in the synovial membrane of osteoarthritis. 211 5

On the basis of both 125I-labelled urokinase-like plasminogen activator binding analysis and transmission electron microscopy of an urokinase-gold complex, we have shown the presence of specific receptors for human urokinase on the cell membrane of human synovial cells. By radio-ligand binding experiments we have shown the existence of similar receptors on the surface of human chondrocytes. In both cases the specific binding is attributable to interaction between the receptor and the A chain of the ligand, as previously shown in other cell model systems. Treatment of synoviocytes with 1,8-diacetoxy-anthraquinone-3-carboxylic acid (diacetylrhein) is able to reduce the number of surface urokinase receptors. At the same time the drug can reduce the fibrinolytic activity released into the culture medium of human synovial cells. Preliminary data indicate that chondrocytes from osteoarthritic patients have a larger number of urokinase receptors than chondrocytes of normal patients. Diacetylrhein can restore the receptor number to normal levels; the amount of urokinase in the synovial fluid of ostroarthritic patients is also reduced. We conclude that the use of this drug has the chance to significantly modify the natural history of osteoarthritis.
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PMID:Modulation of urokinase receptors on human synovial cells and osteoarthritic chondrocytes by diacetylrhein. 217 Feb 88

Activity of plasminogen activator in synovial fluids of patients with osteoarthritis was determined by a radial diffusion assay. Synovial fluid from human knee joints was obtained by joint lavage with 35 ml physiological saline containing 0.5% hydroxyethyl starch. Synovial fluids from contralateral, healthy knee joints served as controls. The activity of plasminogen activator in synovial fluid from activated (painful) osteoarthritis is significantly higher than in cases of latent osteoarthritis, whereas the activity of controls is significantly lower as in latent osteoarthritis. The findings are helpful for the discovery of patients with enhanced plasminogen activator levels in synovia which should be treated therapeutically.
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PMID:[Plasminogen activator activity of the synovial fluid as an indicator of activation phenomena in degenerative joint diseases]. 260 96

The plasminogen activator (PA) and plasminogen activator inhibitor (PAI) in synovial fluid (SF) of osteoarthritis (OA) were examined to clarify their pathophysiological roles in this disease. Three PAs with molecular weights of 90K, 55K, and 33K were found in the SF, but the 55K PA was dominant. Immunologically, both the 55K and 33K PA were u-PA, while the 90K PA was t-PA. The PAI reacted against both u-PA and t-PA, but the PAI activity against u-PA was much stronger. Urinary trypsin inhibitor (UTI) made a complex with the 55K PA and suppressed the PA activity. A clinical study in which UTI was injected into the joint space of OA (18 joints in 15 patients) revealed excellent (39%), good (16%), and fair (44%) results based on assessment of the pain, range of motion, ballottement and activity of daily living.
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PMID:Effect of urinary trypsin inhibitor on osteoarthritis. 314 65

Interleukin-1 (IL-1) treatment of synovial cells from rheumatoid arthritis and osteoarthritis patients resulted in a dose-dependent secretion of phospholipase A2 (PLA2). IL-1 also stimulated prostaglandin E2 and plasminogen activator synthesis, in parallel with PLA2 activation; all 3 were detectable within 6 hours of IL-1 treatment and peaked by 24 hours. Synovial cell PLA2 required calcium (5 mM) and a neutral pH (7.5) for maximal activity and appears similar to the PLA2 in synovial fluid, which has been described previously. We conclude that PLA2 can be induced by IL-1, and its secretion may contribute significantly to the inflammatory actions of IL-1.
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PMID:Interleukin-1 activates phospholipase A2 in human synovial cells. 325 70

The plasminogen activator in synovial fluid from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) was analyzed on a molecular basis. The level of plasminogen activator in RA was found to be higher than in OA. The plaminogen activators of both RA and OA revealed 3 different molecular weights: 90,000, 55,000 and 33,000. RA demonstrated the 3 plasminogen activators in broadly comparable ratios, but OA had the 55,000 form dominantly. The 90,000 plasminogen activator was a tissue-type plasminogen activator, while the 55,000 and 33,000 plasminogen activators were of the urokinase-type. beta-Methasone suppressed the tissue-type plasminogen activator, and urinary trypsin inhibitor suppressed the urokinase-type plasminogen activators. When urinary trypsin inhibitor was injected clinically into the joint space of a patient with RA, the urokinase-type plasminogen inhibitor was suppressed as in the in vitro study, and the clinical signs and symptoms were markedly improved. Open trials of intraarticular injections of urinary trypsin inhibitor demonstrated improvement of the clinical signs and symptoms.
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PMID:Plasminogen activator in synovial fluid from patients with rheumatoid arthritis. 362 26

The enzyme inhibitors alpha 2 macroglobulin (alpha 2M) and alpha antitrypsin (alpha 1AT) have been demonstrated previously in the pannus-cartilage junction area in 12 patients with rheumatoid arthritis (RA). These deposits were present in both inflammatory cells and in the cartilage matrix. As the tissue studied came from far advanced disease removed at the time of joint replacements, the initial phase of cartilage destruction was studied in a carrageenin-induced arthritis in rabbits. Sequential studies indicated that loss of proteoglycan from cartilage was necessary before alpha 2M penetrated the matrix. Explant cultures of synovial tissue from RA and osteoarthritis (OA) joints released an inhibitor of neutrophil elastase and plasminogen activator which was neither alpha 2M nor alpha 1AT. Synovial tissue (and cartilage) enzyme inhibitors may have important implications in relation to protective mechanisms within the joint in RA and OA over and above the effect of plasma inhibitors.
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PMID:The distribution of enzyme inhibitors in the joint in rheumatoid and experimental arthritis. 608 87


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