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 plasminogen activator exists in the human placenta (PPA) as a reversible complex with its inhibitor (UKI). Plasminogen activating activity appeared resulting from the separation of UKI from PPA-UKI complex through UK-Sepharose or UK-Affi Gel 10 affinity chromatography. This crude PPA was purified through gel filtration on Sephadex G-150 and DEAE-Sephacel column chromatography. The purified PPA was obtained at a rate of 25 micrograms from one placenta, the specific PA activity of which was 21, 071 IU/mg-protein. The molecular weight of PPA was estimated at about 65,000 (unreduced) by SDS-polyacrylamide gel electrophoresis. PPA did not react to the anti-UK serum and UK did not react to the anti-PPA serum. It is revealed that PPA has a smaller influence on fibrinogenolysis than UK does. PPA is a new plasminogen activator in the human placenta, which has different properties from UK biologically and immunologically. It is speculated that in the near future PPA will be one of the tissue activators in thrombolytic therapy for thrombotic diseases including toxemia. We note that the measurement of the plasma PPA level is useful as one of the marker proteins of placental function and malignant tumors.
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PMID:Purification and characterization of placental plasminogen activator (PPA). 392 41

Pure cultures of bovine endothelial cells (EC) produce and secrete large amounts of plasminogen activators (PA). Cocultivation of EC with vascular smooth muscle cells (SMC) resulted in a significant decrease of PA activities secreted by the EC, whereas the cellular PA activities remained unaffected. Secreted PA activities were absent in the growth medium as long as the SMC to EC ratio was 2:1 or higher. The PA inhibitory activity of the SMC was rapid and cell-to-cell contact was not necessary. The PA inhibitory activity was present in homogenates of SMC as well as in the medium conditioned by them but not in the extracellular matrix elaborated by these cells. Serum free medium conditioned by SMC neutralized both tissue type (t-PA) and urokinase like (u-PA) plasminogen activators. Gel electrophoretic analysis of SMC conditioned medium followed by reverse fibrin autography demonstrated PA inhibitory activities in the molecular weight (Mr) range of 50,000 to 52,000 similar to those present in media conditioned by bovine endothelial cells or fibroblasts. Regular fibrin zymography of SMC conditioned medium incubated with u-PA or t-PA revealed the presence of a component with a calculated approximate Mr of 45,000 to 50,000 which formed SDS resistant complexes with both types of PA. These data demonstrate that vascular SMC produce and secrete (a) inhibitor(s) of PAs which may influence the fibrinolytic potential of EC.
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PMID:Vascular smooth muscle cells inhibit the plasminogen activators secreted by endothelial cells. 392 3

Newborn rat cerebellum microexplants cultured in Minimal Essential Medium with glucose and insulin released plasminogen activator (PA), which was detected in living cultures by a substrate overlay assay. Gel electrophoresis of cerebellum-conditioned medium followed by zymography resolved PA activity in two separate bands of 48,000 and 75,000 daltons apparent mol. wt. Using specific antisera, these bands were shown to be respectively urokinase and tissue-type PA. Cerebellum conditioned medium as well as purified human urokinase induced the proliferation and outgrowth of glial fibrillary acid protein-positive cells from newborn cerebellar microexplants. The effect was suppressed by the serine protease inhibitor phenyl methanesulfonylfluoride. Since PAs are most likely of neuronal origin, we suggest that at least one of these proteases acts as a neuronoglial mitogenic signal during development.
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PMID:Plasminogen activator is a mitogen for astrocytes in developing cerebellum. 403 64

Human extrinsic plasminogen activator (EPA), highly purified from a melanoma cell culture fluid is inactivated in human plasma with a half-life (t 1/2) of 90-105 min. Gel filtration on Ultrogel AcA 34 of mixtures of 125I-labeled EPA and human plasma, incubated at 37 degrees C, revealed the progressive formation of two radioactive components, one with an apparent Mr of 150,000 and one eluting at the void volume. The component with an Mr of 150,000 was identified as consisting at least in part of EPA-alpha 2-antiplasmin complex since: 1) it reacted with antibodies against alpha 2-antiplasmin, but not with antibodies against the other known plasma protease inhibitors, and 2) formation of this component was strongly reduced in plasma specifically depleted in alpha 2-antiplasmin or when the active site of EPA was blocked. The component eluting at the void volume was identified as consisting at least in part of EPA-alpha 2-macroglobulin complex since: 1) it only reacted with antibodies against these two proteins and 2) was not formed in plasma depleted in alpha 2-macroglobulin or when the active site of EPA was blocked. In purified systems alpha 2-antiplasmin inhibited one-chain EPA with a rate constant of 60 M-1s-1 and two-chain EPA with a rate constant of 130 M-1s-1, which corresponds to a t 1/2 in plasma of 180 min or 90 min, respectively. alpha 2-Macroglobulin inhibited one-chain EPA with a rate constant of 15 M-1s-1 and two-chain EPA with a rate constant of 30 M-1s-1, which corresponds to a t 1/2 in plasma of 4 or 2 hrs. All these findings taken together indicate that EPA is slowly neutralized in human plasma primarily by alpha 2-antiplasmin and to a lesser extent by alpha 2-macroglobulin. There appears to be no specific inhibitor in human plasma, which would inactivate EPA either rapidly or to a significant extent.
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PMID:Neutralization of human extrinsic (tissue-type) plasminogen activator in human plasma: no evidence for a specific inhibitor. 617 7

Incubation of plasminogen-free rat citrated plasma with acetone (23% v/v) yielded enzyme preparations with high levels of plasminogen activator (PGA) and kininogenase (kallikrein), but with a low concentration of high molecular weight kininogen (HMWK) active as cofactor for kaolin-induced activation of factor XII. When benzamidine (4.0 mM) was present during acetone activation, a high yield of functionally active HMWK was obtained. Gel chromatography separated PGA into one high molecular weight fraction (HMW-PGA) without kininogenase and BAEe esterase activity, and one fraction (LMW-PGA) eluting together with plasma kallikrein. Injection of dextran (100 mg/kg intravenously) reduced the amount of LMW-PGA to 40%, without altering the concentration of HMW-PGA, and with only a small reduction of the kininogenase activity.
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PMID:Dextran-induced lowering of plasminogen proactivator and functionally active high molecular weight kininogen in the rat. 618 May 97

Most reports in the literature state that human plasma kallikrein does not destroy the capacity of human high molecular weight kininogen (HMrK) to function as a cofactor in the contact phase activation of factor XII. In the present work preparations of highly purified human plasma kallikrein that showed high plasminogen activator (PGA) activities rapidly reduced the cofactor function of human HMrK. Gel electrophoresis with SDS without reduction showed that all kallikrein preparations tested contained two protein bands, one major band with a Mr of about 83,000, and one weak band with a Mr of 80,000. The main band is probably identical with kallikrein I, which Levison & Tomalin (1982b), using Ac-Pro-Phe-Arg-OMe-HCl as substrate, found to be ten times more active (in terms of kcat/Km) than kallikrein II with Mr 3000 daltons lower. The rate of HMrK destruction in our experiments varied with the kallikrein preparation used, but assays of their hydrolytic activities against benzoyl arginine ethylester (BAEe) or the plasma kallikrein selective tripeptide substrate H-D-Pro-Phe-Arg-pNA (S-2302) did not discriminate between enzyme preparations with different HMrK-destroying capacities. Assay of PGA activities demonstrated a correlation between the level of PGA measured, and the HMrK-destroying capacity.
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PMID:Reduced cofactor function of human high molecular weight kininogen induced by human plasma kallikrein. 643 52

Plasminogen activator was measured in the ventral prostates of non-castrated, castrated, and androgen-treated rats to determine whether changes in this activity correlated with the process of glandular involution. While the activity was very low in cytosolic extracts from the prostates of non-castrated rats, 2 days following castration the plasminogen activator activity increased in a near-linear fashion such that by day 7 it was 10-fold higher in terms of specific activity (per mg of protein) and cellular concentration (per mg of DNA). During this interval there was a rapid decrease in the cell population of the prostates. Treatment of the 7-day castrated rats with the potent androgen, dihydrotestosterone, both reduced the plasminogen activator activity and restored the cell number in a dose-related manner. Gel electrophoretic analysis revealed two major bands of plasminogen activator activity in the cytosolic extracts from 4- and 7-day castrated rats, plus additional minor bands in samples from 10- and 14-day castrated rats. Approx. 10% of the cellular concentration of plasminogen activator activity was recovered in association with an 18000g pellet fraction from the prostates; this fraction showed less heterogeneity of the plasminogen activator forms as observed by gel electrophoresis. Inhibitor studies indicated that the 18000g pellet fraction from the prostates of non-castrated rats possessed some plasminogen activator inhibitor activity, but the relative concentration of the inhibitor activity was small. We conclude that the involution of the prostate is probably associated with increased synthesis of plasminogen activators through a de-repression process which may involve loss of androgen receptors.
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PMID:Increased activity of plasminogen activators during involution of the rat ventral prostate. 643 69

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.
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PMID:Complexes between tissue-type plasminogen activator and proteinase inhibitors in human plasma, identified with an immunoradiometric assay. 668 24

The plasminogen activator liberated by cells of human neuroblastoma strain SK-N-SH was purified up to 400-fold, with a 40% recovery of activity, by a relatively simple procedure. This involved (NH4)2SO4 precipitation, followed by chromatography on both Affi-Gel Blue and p-aminobenzaminidine-Sepharose. The SK-N-SH activator was shown to differ from human urokinase with respect to immunological specificity, the molecular weights and isoelectric points of their enzymatically active species, the ability to be activated by fibrin and their relative sensitivities to inactivation by diisopropyl fluorophosphate. The average molecular weights of the enzymatically active species derived from strain SK-N-SH were shown to be 66,500, 64,500, 60,500 and 37,500. In the presence of fibrin, the SK-N-SH plasminogen activator appeared to be stimulated approximately 16-fold, with no apparent stimulation of urokinase activity. Urokinase is inactivated by diisopropyl fluorophosphate at a rate 6.4-fold faster than that of the SK-N-SH activator.
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PMID:Characterization and partial purification of the plasminogen activator from human neuroblastoma cell line, SK-N-SH. A comparison with human urokinase. 705 33

The turnover of highly purified human extrinsic plasminogen activator (EPA) (one- and two-chain form) was studied in rabbits. Following intravenous injection, EPA-activity declined rapidly. The disappearance rate of EPA from the plasma could adequately be described by a single exponential term with a t 1/2 of approximately 2 min for both the one-chain and two-chain forms of EPA. The clearance and organ distribution of EPA was studied by using 125I-labeled preparations. Following intravenous injection of 125I-labeled EPA the radioactivity disappeared rapidly from the plasma also with a t 1/2 of approximately 2 min down to a level of 15 to 20 percent, followed by a small rise of blood radioactivity. Gel filtration of serial samples revealed that the secondary increase of the radioactivity was due to reappearance of radioactive breakdown products in the blood. Measurement of the organ distribution of 125I at different time intervals revealed that EPA was rapidly accumulated in the liver, followed by a release of degradation products in the blood. Experimental hepatectomy markedly prolonged the half-life of EPA in the blood. Blocking the active site histidine of EPA had no effect on the half-life of EPA in blood nor on the gel filtration patterns of 125I in serial plasma samples. It is concluded that human EPA is rapidly removed from the blood of rabbits by clearance and degradation in the liver. Recognition by the liver does not require a functional active site in the enzyme. Neutralization in plasma by protease inhibitors does not represent a significant pathway of EPA inactivation in vivo.
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PMID:Turnover of human extrinsic (tissue-type) plasminogen activator in rabbits. 719 2


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