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 persistency of fibrin deposits in the kidney during renal diseases could reflect either a defective release of plasminogen activators (PA) or a local excess of PAI. In order to investigate this question, we studied human renal biopsies by immunofluorescence technique with specific antibodies for fibrin, tissue-type plasminogen activator (t-PA), urokinase (u-PA), PAI-1 and PAI-2. By this technique t-PA could be detected in the glomerular flocculus and the endothelium of small arteries of the normal control kidneys. We failed to detect significant fluorescence with other antibodies in normal kidneys. Conversely, in cases of vascular nephropathy with thrombosis the positive fluorescence obtained with anti-fibrin antibodies at the site of thrombosis was associated with a positive fluorescence with anti-PAI-1 and to a lesser extent with anti-t-PA antibodies. u-PA and PAI-2 were not detected in these lesions. Similarly in the most severe forms of crescentic glomerulonephritis, extracapillary fibrin deposits were associated with PAI-1. In one case u-PA was also detected. This is in agreement with our previous findings that glomerular epithelial cells release both PAI-1 and the inactive form of u-PA (pro u-PA). Thus, our results support the hypothesis that PAI-1, which is able to inhibit both t-PA and u-PA, may play a major role in the persistency of fibrin deposits in the human kidneys during pathological conditions.
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PMID:Plasminogen activator inhibitor 1 in renal fibrin deposits of human nephropathies. 210 50

The effect of fibrin stimulation on the fibrinolytic potential in cultured human umbilical vein endothelial cells (HUVEC) was investigated in the normal state and aged state. The amount of antigen of the two fibrinolytic factors, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1), was determined using ELISA and the ABC method, respectively. When a fibrin clot was overlayered on the normal HUVEC, the secretion of t-PA or PAI-1 from the HUVEC was greatly changed. That is, PAI antigen was decreased 3-fold and t-PA antigen increased slightly in the conditioned medium. On the other hand, when the aged HUVEC were stimulated by a fibrin clot, PAI antigen was increased 3-fold and t-PA antigen did not change in the conditioned medium. When the level of fibrinolytic activity in the conditioned medium was expressed as the molar ratio of PAI and t-PA (PAI/t-PA), the value in the fibrin-stimulated normal HUVEC was markedly reduced (a 3.5-fold decrease) when compared with that of the non-stimulated normal HUVEC, reflecting a profibrinolytic state. On the other hand, the value in the fibrin-stimulated aged HUVEC was markedly increased (a 5-fold increase) when compared with that of the non-stimulated aged HUVEC, reflecting an antifibrinolytic state. Actinomycin D- or cycloheximide-treated HUVEC showed no response to the fibrin stimulation. We conclude that the level of HUVEC-mediated fibrinolytic activity was regulated mainly by the production and secretion of PAI from the HUVEC to protect against the generation of thrombi. In the aged HUVEC, the regulatory mechanism acts in an opposite manner and a thrombotic process may be induced.
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PMID:Suppression of plasminogen activator inhibitor 1 release by fibrin from human umbilical vein endothelial cells. 210 96

The effects of thrombin, interleukin-1 (IL-1), tumor necrosis factor (TNF) and gamma-interferon (gamma-IFN) on the release of plasminogen activator (PA) and inhibitor (PAI) were studied using cultivated human glomerular epithelial cells (GECs). Species of PAs and PAI secreted from the GECs were urokinase-type PA (u-PA) and tissue-type PA (t-PA), while the major species was a single chain u-PA in the amount of 28.6 +/- 2.34 ng/10(5) cells for 24 hours (N = 4, mean +/- SD), and PAI-1. The addition of increased concentrations of thrombin (0.1 to 31.6 U/ml) into confluent cultures enhanced the GECs to release u-PA, t-PA and PAI-1 in a dose- and time-dependent manner. The incubation of the GECs with 10 U/ml thrombin resulted in about a fourfold increase in the concentration of u-PA, threefold in t-PA and twofold in PAI-1. All thrombin effects, however, were suppressed by the simultaneous addition of cycloheximide, indicating that the enhancing effects of thrombin were due to an increase in the production of PAs and PAI-1, via protein synthesis. These thrombin effects appeared to be dependent upon the enzymatically active site of thrombin because DFP-thrombin had no effect. In the conditioned medium which was under continuous thrombin stimulation for 24 hours, no u-PA activity was detectable, even after the plasmin treatment, because a single chain u-PA was degraded by the thrombin. The stimulation of cultured GECs with thrombin only for the first three hours in 24 hour cultivation showed an apparent increase in the antigenic amount of u-PA. IL-1 enhanced the release of t-PA and PAI-1, and TNF did that of u-PA and t-PA, while gamma-IFN showed no significant effects. These findings indicate that the GECs participate in the regulation of extracapillary fibrinolysis in the glomerular microenvironment, as being modulated by thrombin and two cytokines, IL-1 and TNF.
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PMID:Secretion of plasminogen activator and its inhibitor by glomerular epithelial cells. 211 68

The tissue-specific distribution of tissue-type and urokinase-type plasminogen activator (t-PA and u-PA) and their inhibitor type 1 (PAI-1) was analyzed at mRNA level in five major rat organ tissues. t-PA mRNA was detected in lung, kidney, heart, and liver. u-PA mRNA was detected in kidney and lung. Presence of PA mRNA correlated with the detection of PA activity in extracts of these tissues. PAI-1 mRNA was detected predominantly in heart and lung. Although PAI activity could not be measured directly in tissue extracts, the presence of PAI-1 mRNA correlated with the occurrence of PA.PAI complex in fibrin autography of tissue extracts. Endotoxin injection caused a very large increase in plasma PAI activity. This increase correlated with a marked increase in PAI-1 mRNA in nearly all tissues studied. The increase in PAI-1 mRNA is most pronounced in lung and liver. Endotoxin injection also caused an increased level of t-PA mRNA in heart and kidney, and an increased u-PA mRNA level in kidney. mRNA analysis of freshly isolated and separated subfractionated liver cells showed that the marked increase in PAI-1 mRNA in the liver after endotoxin injection may be due mainly to a strong increase of PAI-1 mRNA in the liver endothelial cells.
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PMID:Endotoxin induction of plasminogen activator and plasminogen activator inhibitor type 1 mRNA in rat tissues in vivo. 211 27

Increased plasma levels of plasminogen activator inhibitor-1 (PAI-1) have been shown to exist in 40 to 60% of patients with stable coronary artery disease and have been suggested to be responsible for the development of coronary thrombotic complications. However, it is also discussed whether PAI-1 elevation might mainly be due to variables like increased age or to reactive mechanisms caused e.g. by the chest pain itself. To exclude age dependent or pain related influences, age-matched patients with stable angina pectoris (NHYA II) and angiographically proven coronary artery disease (CAD, n = 16) or without evidence for coronary sclerosis (variant angina, n = 10; angina-like syndrome with normal coronary angiogram, n = 5; non-CAD, n = 15) have been investigated for their plasma PAI-1 activity and t-PA antigen levels. The mean PAI activity in CAD patients (17.5 U/ml) was significantly higher than in non-CAD patients (9.6 U/ml) (p less than 0.0001). In the CAD patients no significant variation in plasma PAI-1 values could be demonstrated when related to the extent of the disease or to a history of previous myocardial infarction. t-PA antigen was also elevated in CAD patients as compared to the non-CAD group (p less than 0.02). The results suggest therefore a strong correlation between coronary artery disease itself and elevated levels of components of the plasma fibrinolytic system.
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PMID:Plasminogen activator inhibitor-1 levels in patients with chronic angina pectoris with or without angiographic evidence of coronary sclerosis. 211 22

The venous occlusion test was applied to 17 patients with inflammatory bowel disease (IBD; 7 cases of Crohn's disease, 10 cases of ulcerative colitis). Results were compared to those obtained in 20 healthy matched control subjects. Patients with IBD had significantly decreased t-PA Ag release (p less than 0.001) and had no significant vWF Ag release. Residual PAI activity was evidenced after venous stasis in the IBD group but not in the control group. Hypofibrinolysis was more important in patients with an evolutive IBD than in patients with IBD in remission. Impaired systemic fibrinolytic capacity might contribute to an increased risk for thromboembolic complications and to the pathogenesis of inflammatory bowel disease.
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PMID:Impaired fibrinolytic capacity in patients with inflammatory bowel disease. 211 29

The generation of D-dimer was studied in the course of local thrombolytic therapy of peripheral arterial occlusions with low doses of recombinant human tissue-type plasminogen activator (rt-PA) in 7 patients. Intermittent local application of rt-PA resulted in a marked increase in D-dimer exceeding values usually seen after intravenous application of manifold higher doses used in myocardial infarction. The increase in D-dimer was related to the estimated thrombus size (length of the occlusion) and the total dose of rt-PA applied. During local rt-PA infusion of 6 of 7 patients maintained plasminogen activator inhibitor capacity (PAI-cap) between 34% and 79% of their corresponding pre-treatment levels; detectable levels of PAI-cap in circulating blood during the procedure did not interfere with the success of therapy.
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PMID:D-dimer in local thrombolytic therapy with low doses of recombinant human tissue-type plasminogen activator (rt-PA) in patients with peripheral arterial occlusive disease. 212 70

Plasma tissue-type plasminogen activator and plasminogen activator inhibitor were determined during the acute, recovery and sequelae stages of patients with ischemic stroke by chromophoric substrate assay. The result showed that t-PA activity was elevated during the acute phase, remained elevated during the recovery stage and declined during the sequelae stage. Lowering of PAI activity was found during acute phase, which reversed during recovery phase and remained significantly elevated during sequelae stage. As a result, the ratio of PAI/t-PA fluctuated during different stages of the disease. Significant elevation of PAI and PAI/t-PA ratio during sequelae stage may be one of the risk factors of further thrombosis and contribute partly to the high relapsing rate of the disease. In addition, a positive correlation was found between PAI and serum cholesterol content.
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PMID:[Determination of plasma tissue type plasminogen activator and plasminogen activator inhibitor activity in patients with ischemic stroke]. 212 60

Tissue-type plasminogen activator (PA) activity and antigen was measured in nine different tissues from healthy rats (brain, lung, heart, liver, spleen, kidney, adrenal, aorta and skeletal muscle). After extraction in a KSCN buffer (for kidney) or in an acid acetate buffer (for all other tissues), total PA activity was determined by an improved spectrophotometric procedure, and tissue-type PA (tPA) activity was determined by quenching with anti-rat tPA Ig; tPA antigen was determined by an ELISA procedure. tPA was the major PA (greater than 90%) in all tissues, except kidney and liver (65%) and spleen (40%). Lung yielded the highest tPA activity (1400 U/g), followed by kidney, brain, heart and adrenal (150-300 U/g), and then by liver, aorta, spleen and muscle (15-30 U/g). In agreement with fibrin autographic studies, which demonstrated the presence of tPA-PAI complexes in the tissue extracts, the tPA antigen/activity ratio was generally greater than one. Free PA inhibitor activity could not be demonstrated in any tissue.
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PMID:Distribution of tissue-type plasminogen activator (activity and antigen) in rat tissues. 213 39

Endothelial cells play an important role in the regulation of fibrinolysis by the production of several key regulatory proteins. The cytokines tumor necrosis factor (TNF), lymphotoxin, and interleukin-1 (IL-1), but not interleukin-6, increase the production of plasminogen activator inhibitor-1 (PAI-1) by endothelial cells, whereas they have no stimulatory effect on the production of tissue-type plasminogen activator (t-PA). Primary cultures of human endothelial cells release very little urokinase-type plasminogen activator (u-PA). We report here that TNF and lymphotoxin induce, in a concentration-dependent way, the production of both cellular and secreted u-PA antigen in primary and subcultured human endothelial cells. The TNF-induced increase was accompanied by a more than 10-fold increase in u-PA mRNA. Upon stimulation of early passage umbilical vein endothelial cells by TNF, u-PA was predominantly secreted at the basolateral side, whereas PAI activity and t-PA were found in more equal amounts at the apical and basolateral sides of the cell monolayers. TNF-stimulated u-PA secretion by subcultured human aorta endothelial cells showed only a marginal polarity. The u-PA antigen was present in a plasmin-activatable form (single chain u-PA) and in a nonactivatable form (probably u-PA: PAI-1 complex). During the induction of u-PA by TNF, the ratio between plasmin-activatable u-PA and total u-PA decreased markedly. This may indicate that TNF also increases the degree of u-PA activation. The parallel induction of the synthesis and secretion of both u-PA and PAI-1 by endothelial cells adds a new aspect to the alterations of the fibrinolytic system caused by inflammatory mediators. This aspect may be significant for the regulation of cell-associated and interstitial plasminogen activator activity.
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PMID:Tumor necrosis factor induces the production of urokinase-type plasminogen activator by human endothelial cells. 214 60


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