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

Chicken embryo fibroblasts (CEF) transformed by Rous sarcoma virus (RSV) exhibit increases in both a cell-associated and a secreted form of plasminogen activator (PA). The mechanism whereby the membrane-bound, cell-associated form of PA is processed to an extracellular, soluble form has been examined in cultures of chicken fibroblasts transformed by a temperature-sensitive mutant of RSV. We report that chymostatin, a protease inhibitor of limited specificity, inhibits the release of PA from tsRSVCEF while causing accumulation of cell-associated PA. Chymostatin's effect on PA release is specific, reversible and appears to be due to its anti-proteolytic capacity. Chymostatin does not inhibit cellular protein synthesis or interfere in the assay used to measure PA. A chymostatin-sensitive protease activity has been found in a membrane fraction isolated from tsRSVCEF.
 ...
PMID:Inhibition of plasminogen activator release from transformed chicken fibroblasts by a protease inhibitor. 627 25

Levels of plasminogen activator activity were determined in testes obtained from normal and irradiated rats in various ages. During normal development, plasminogen activator activity per g testis increased rapidly between 40 and 60 days of age, but a comparable rise did not occur in germ-cell depleted testes of irradiated rats. Levels of enzyme in various populations of testicular cells were highest in Sertoli (varying between 1800 and 6300 units/mg protein in cell maintained under different culture conditions), and lowest in peritubular myoid cells (about 1 unit/mg protein), with intermediate levels in germinal cells (ranging between 147 and 560 units/Mg protein in residual bodies, spermatocytes and spermatids). No protease inhibitor could be detected in germ-cell extracts. The addition to the medium in which Sertoli cells were in culture of particles which can be phagocytosed (autoclaved E. coli) resulted in an increased formation of plasminogen activator activity by Sertoli cells. A synergistic enhancement of enzyme production resulted following the addition of submaximal quantities of dibutyryl cyclic AMP and autoclaved bacteria to sertoli cells in culture. On the basis of these data, we suggest that the presence of advanced germinal cells during gonadal development may stimulate the synthesis of plasminogen activator by Sertoli cells, mediated in part by the phagocytosis of residual bodies by sertoli cells which occurs prior to spermiation.
 ...
PMID:Changes in levels of plasminogen activator activity in normal and germ-cell-depleted testes during development. 628 Oct 97

Confluent cultures of bovine aortic endothelial cells (BEC) were found to secrete both tissue type plasminogen activator (t-PA) and urokinase type plasminogen activator (u-PA). Exposure of the cultures to increasing concentrations of dexamethasone resulted in a time and concentration dependent inhibition of cellular and secreted u-PA. Complete inhibition of u-PA production and secretion was found at dexamethasone concentrations of 10(-8) molar or higher. Several distinct PA forms with molecular weights ranging from 10,000-20,000 to greater than 200,000 were found in the conditioned medium of untreated BEC cultures. After addition of dexamethasone (10(-7) molar) to the culture medium the PAs with molecular weights of 117,000, 58,000, 47,000, were absent suggesting that they were u-PAs, whereas the PAs with molecular weights of greater than 200,000 and 75,000 remained unchanged suggesting their t-PA origins. The PAs with lower molecular weights of 35,000, 28,000 and 10,000 to 20,000 were most likely generated from the higher molecular weight forms by limited proteolysis since they were absent when the medium was conditioned in the presence of the protease inhibitor Trasylol. The two PA types may therefore be independently regulated in BEC.
 ...
PMID:Glucocorticoids inhibit plasminogen activator production by endothelial cells. 642 Sep 27

The absence of fibrinogen and the presence of plasmic fragments X, Y, D, and E were demonstrated in a patient bitten by a western diamondback rattlesnake, Crotalus atrox. The factor VIII level and the platelet count were within normal limits. There were distinct changes of protease inhibitors in the patient's plasma. Alpha-1-protease inhibitor was elevated. Antithrombin-III was only slightly decreased after the envenomation, but alpha 2-antiplasmin and alpha 2-macroglobulin were initially significantly lowered, returning to normal values in 38 and 3 days, respectively. Plasmin-alpha 2-antiplasmin complex was present until day 10 after the envenomation. However, purified plasminogen was not activated in vitro by the venom. Cultured endothelial and smooth muscle cells from human blood vessels released an increased amount of plasminogen activator upon incubation with the venom. The release did not result from cell lysis. Platelets in normal human platelet-rich plasma were aggregated by 10 micrograms/ml of the venom, without serotonin secretion. The aggregation kinetics and serotonin secretion induced by adenosine diphosphate (ADP) or arachidonate were not significantly affected by the venom at 1-10 micrograms/ml. It is concluded that the predominant mechanism of afibrinogenemia in the patient after Crotalus atrox bite resulted from primary fibrinogenolysis and not from a consumptive coagulopathy. The lytic state seemed to be induced through an indirect activation of plasminogen by vascular plasminogen activator, which was probably released from endothelial cells and smooth muscle cells by the snake venom.
 ...
PMID:Fibrinogenolytic afibrinogenemia after envenomation by western diamondback rattlesnake (Crotalus atrox). 653 96

In order to clarify the origin and release mechanism of plasminogen activator in the tracheobronchial secretion of rats, electrophoretic analysis of the secretion and studies on the effects of certain vasoactive drugs on the activator activity in the secretion were carried out. From the results of electrophoretic analysis of the tracheobronchial secretion in non-treated rats, protease inhibitor composed of glycoprotein was not contained in the secretion in contrast to the circulating blood, but a protein of low molecular weight like albumin in the circulating blood was contained in the secretion. Furthermore, after injection of noradrenalin, the blood pressure was temporarily elevated and the fibrinolytic activity of the euglobulin fraction in the circulatory blood was also increased. Subsequent to this elevation of fibrinolytic activity in the circulating blood, the fibrinolytic activity in the tracheobronchial secretion increased. Based on these results, it is suggested that the increase of fibrinolytic activity in the circulating blood was due to increased release of plasminogen activator from the vascular wall, and the increased fibrinolytic activity of the tracheobronchial secretion was caused by a consequent increased transudation of plasminogen activator from the circulating blood into the tracheobronchial lumen.
 ...
PMID:Interaction of fibrinolytic activity between the tracheobronchial secretion and circulating blood of rats. 653 52

Extrinsic (tissue-type) plasminogen activator antigen in human plasma, as measured by a two-site immunoradiometric assay, is composed of a fibrin-adsorbable and a nonadsorbable fraction. Gel filtration on Ultrogel AcA 44 in 1.6M KSCN of the fibrin-adsorbable fraction showed a peak with Mr congruent to 70,000, which contained plasminogen activator activity and was assumed to represent free extrinsic plasminogen activator. The nonadsorbable fraction showed a broad peak with Mr congruent to 140,000 without plasminogen activator activity. Overnight incubation at 37 degrees C of postexercise plasma revealed a shift of the Mr congruent to 70,000 peak to the Mr congruent to 140,000 position, suggesting that the Mr congruent to 140,000 peak consists of extrinsic plasminogen activator-protease inhibitor complex(es). alpha 2-Antiplasmin is the main inhibitor of extrinsic plasminogen activator in plasma 13 and is therefore most probably at least in part responsible for the generation of the Mr congruent to 140,000 component. A possible involvement of other plasma proteinase inhibitors was explored by incubation of 125I-labeled extrinsic plasminogen activator in alpha 2-antiplasmin-depleted plasma. A complex was formed with a t1/2 of about 1 hr, which was identified by immunoprecipitation as extrinsic plasminogen activator-alpha 1-antitrypsin complex. Additional evidence for the presence of extrinsic plasminogen activator complexes with alpha 2-antiplasmin and alpha 1-antitrypsin in plasma was obtained from two-site immunoradiometric assays, in which solid-phase anti-inhibitor antibody bound the corresponding complex, which was then detected with radiolabeled, affinospecific antibody against extrinsic plasminogen activator. It was concluded that plasma contains both free extrinsic plasminogen activator and plasminogen activator complexes with alpha 2-antiplasmin and alpha 2-antitrypsin. These complexes are also present in plasma collected on the active site inhibitor, D-Phe-Pro-Arg-CH 2Cl, at rest and after exercise and are therefore assumed to circulate in vivo.
 ...
PMID:Complexes between tissue-type plasminogen activator and proteinase inhibitors in human plasma, identified with an immunoradiometric assay. 668 24

The plasminogen activator secreted by a cultured human melanoma cell line was purified and compared with urokinase and with tissue plasminogen activator from human uterus. The purification procedure consisted of chromatography on zinc chelate-agarose, concanavalin A-agarose, and Sephadex G-150 in the presence of 0.01% (v/v) Tween 80. The purified material was obtained from the culture medium with a yield of 46% and a purification factor of 263. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed one main band with a molecular weight of about 72,000, and in the presence of reducing agents, two bands of 33,000 and 39,000. Addition of the protease inhibitor Aprotinin to the culture media and column buffers yielded a one-chain plasminogen activator with a molecular weight of about 72,000. One molecule of activator reacted with about one molecular of [3H]diisopropylfluorophosphate. The melanoma plasminogen activator and the uterine tissue plasminogen activator appeared to be very similar on dodecyl sulfate-polyacrylamide gel electrophoresis, amino acid analysis, and amidolytic properties. Both activators bound to fibrin clots, while urokinase did not. In immunodiffusion, as well as in quenching experiments of the fibrinolytic activities, the melanoma plasminogen activator appeared to be immunologically identical with the uterine tissue plasminogen activator, but unrelated to urokinase. All these findings indicate that the plasminogen activator secreted by human melanoma cells in culture is very similar to, or identical with, the plasminogen activator found in normal tissue, but different from urokinase.
 ...
PMID:Purification and characterization of the plasminogen activator secreted by human melanoma cells in culture. 678 58

Hepatic artery thrombosis after orthotopic liver transplantation is a serious complication, especially in children. We report our experience with intensive anticoagulant therapy during and after living-related liver transplantation in pediatric recipients. Twenty-four patients between 5 months and 15 years of age were studied. The mean diameter of the anastomosed hepatic arteries was 2.7 mm. The anticoagulant therapy consisted of low-molecular-weight heparin, antithrombin III concentrates, prostaglandin E1, fresh frozen plasma, and a protease inhibitor. The profiles of the coagulation and fibrinolytic systems were monitored by measuring several parameters, including plasma levels of thrombin-antithrombin III complex, antithrombin III, plasmin-alpha 2 plasmin inhibitor complex, fibrin degradation product D-dimer, tissue type-plasminogen activator, and plasminogen activator inhibitor-1. Acceleration of the coagulation system and delayed recovery of the fibrinolytic system were observed during the early postoperative days. The plasma level of antithrombin III activity was maintained within the normal range by the administration of antithrombin III concentrates. None of the recipients developed hepatic artery thrombosis. Children have been reported to be at a greater risk of developing hepatic artery thrombosis than adults due to the small diameters of their hepatic arteries and the postoperative hypercoagulable state. We believe that the intensive anticoagulation therapy described in this study, the main concept of which is the early correction of imbalance between the coagulant and anticoagulant systems, could become a model for the prevention of hepatic artery thrombosis in pediatric liver transplantation patients.
 ...
PMID:Prevention of hepatic artery thrombosis in pediatric liver transplantation. 748 17

1. The effects of saponin from Ginseng Radix rubra on angiogenesis (tube formation) and its key steps (protease secretion, proliferation and migration) in human umbilical vein endothelial cells (HUVEC) were examined to elucidate the mechanism of the tissue repairing effects of Ginseng Radix rubra. The effect on a wound healing model was also studied. 2. Tube formation was measured by an in vitro system. The activity and immunoreactivity of tissue-type plasminogen activator (tPA) as a protease for angiogenesis and the immunoreactivity of its inhibitor, plasminogen activator inhibitor-1 (PAI-1), were measured in conditioned medium of HUVEC stimulated for 24 h with saponin. Cell proliferation was measured by counting the cell numbers at 2-7 days after seeding. Migration was measured by Boyden's chamber method. The effect on wound healing was studied in the skin of diabetic rats. 3. Saponin at 10-100 micrograms ml-1 significantly stimulated tube formation by HUVEC in a dose-dependent manner. Saponin in a similar concentration-range increased the secretion of tPA from HUVEC as estimated by immunoreactivity and enzyme activity. On the other hand, PAI-1 immunoreactivity was slightly increased at 10 micrograms ml-1 of saponin, but then was significantly decreased at 50 and 100 micrograms ml-1. Cell proliferation was only slightly enhanced by 1-100 micrograms ml-1 of saponin, but migration was significantly enhanced by 10-100 micrograms ml-1 in a dose-dependent manner. Moreover, saponin stimulated wound healing with enhanced angiogenesis in vivo. 4. These results indicate that saponin stimulates tube formation mainly by modifying the balance of protease/protease inhibitor secretion from HUVEC and enhancing the migration of HUVEC, and that it is effective in vivo.
 ...
PMID:Mechanism of angiogenic effects of saponin from ginseng Radix rubra in human umbilical vein endothelial cells. 758 43

The bone resorbing agent, prostaglandin E2 (PGE2), was found to alter several components of the plasminogen activator (PA)/plasmin pathway in primary cultures of rat neonatal osteoblast-like cells. The mRNA and activities of both urokinase-type PA (uPA) and tissue-type PA (tPA) were enhanced by PGE2 treatment. The presence of mRNA for the uPA receptor (uPAR) has been demonstrated in these cells and steady-state levels shown to be greatly enhanced, the response being rapid and sustained for at least 24 hours. mRNA for plasminogen activator inhibitor 1 (PAI-1) was modulated in a biphasic manner, with inhibition of the constitutive level apparent at 4 hours of treatment and stimulation apparent at 12 hours and longer, while PAI-1 protein, measured by an ELISA assay for rat PAI-1, was diminished over this period. Neither PAI-2 mRNA nor mRNA for the broad spectrum protease inhibitor, protease nexin-1 (PN-1), was found to be modulated by PGE2. Therefore, PGE2 is likely to stimulate cell surface proteolytic activity, since uPA mRNA and cell-associated activity were elevated, as was mRNA for the cellular receptor for uPA. Although it was not possible to measure uPAR number and affinity it seems likely that elevated uPAR mRNA would translate into increased uPARs which would localize the increased uPA activity to the pericellular region. tPA mRNA and activity were also increased transiently with the activity inhibited with prolonged incubations, apparently by PAI-1. Elevation of tPA mRNA and activity may result in elevated activity within the extracellular matrix as tPA has been reported to associate with several matrix proteins. Thus the early effect of PGE2 would be to promote proteolysis, both pericellularly and in the extracellular matrix. The inhibition of PAI-1 mRNA and protein, which would contribute to the elevation of activity, is due to PGE2, but the later stimulatory effect on PAI-1 mRNA may be due to feedback regulation by transforming growth factor beta (TGF beta), secreted by osteoblasts and activated by elevated levels of PA.
 ...
PMID:Prostaglandin E2 regulates production of plasminogen activator isoenzymes, urokinase receptor, and plasminogen activator inhibitor-1 in primary cultures of rat calvarial osteoblasts. 759 31


<< Previous 1 2 3 4 5 6 Next >>