Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Plasminogen activator inhibitor activity (PAI), PAI-1 and PAI-2 antigen, and other fibrinolytic parameters were evaluated in amniotic fluid during normal pregnancy and compared with that obtained in plasma of pregnant women. The results indicate the presence of both PAI-1 and PAI-2 in amniotic fluid during normal pregnancy. In amniotic fluid, PAI-1 antigen levels increased from 194 +/- 109 ng/ml (first trimester) to 640 +/- 396 ng/ml (third trimester) and PAI-2 antigen levels increased from 72 +/- 57 ng/ml to 173 +/- 97 ng/ml. In contrast, a decrease in tissue-type plasminogen activator (t-PA) antigen level was observed during pregnancy. The PAI-1 levels in amniotic fluid were significantly higher than the PAI-1 levels in plasma of women at a similar gestational age. However, PAI activity, measured using single chain t-PA, was lower in amniotic fluid than in plasma of normal pregnant women. The PAI activity/PAI-1 antigen ratio in amniotic fluid after activation by a denaturing agent increased from 0.003 +/- 0.004 to 0.059 +/- 0.018. These results indicate that high levels of PAI-1 are present in amniotic fluid and suggest that this PAI-1 is present in a latent form that can be reactivated, at least partially, by a denaturing agent.
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PMID:Plasminogen activator inhibitors type 1 and type 2 and plasminogen activators in amniotic fluid during pregnancy. 212 78

Plasminogen activator inhibitor type-1 (PAI-1) can modify fibrinolytic activity in vitro and in vivo. The present study was performed to determine whether pharmacologic concentrations of tissue-type plasminogen activator (t-PA) can initiate negative feedback by stimulating PAI-1 synthesis. In both human hepatoma cells (Hep G2) and human umbilical vein endothelial cells (HUVEC), t-PA increased the total concentrations and appearance of newly synthesized protein in conditioned media of free PAI-1 and PAI-1 complexed with t-PA in a dose and time dependent fashion judging from results after immunoprecipitation of metabolically labeled PAI-1. The t-PA effect was not attributable simply to release of stored or matrix-bound PAI-1. In HUVEC, Northern blot analyses indicated that t-PA increased steady-state levels of PAI-1 mRNA two-fold. In contrast PAI-1 mRNA expression was not increased in Hep G2 cells. Thus, mechanisms of stimulation appeared to differ in the two cell lines. The results obtained are consistent with the hypothesis that increased PAI-1 synthesis and secretion in response to t-PA may limit or attenuate fibrinolysis locally or systemically in vivo.
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PMID:Induction of synthesis of plasminogen activator inhibitor type-1 by tissue-type plasminogen activator in human hepatic and endothelial cells. 212 71

Plasminogen activator (PA) is a key enzyme in control of the cascade of extracellular proteolytic activities, proteases that degrade the extracellular components. Mammalian cells produce two molecular forms of PA, the urokinase type (u-PA) and the tissue type (t-PA); the u-PA type enzyme regulates cell migration/invasion and related tissue plasticity events. Thus, these plasticity properties of cells are defined by their PAs' biochemical profiles. The capacity of the differentiating glial cells of the central nervous system (CNS) to express and regulate the two types of PA activities has been examined as a function of cell age in culture. Results of the study suggest that only the immature astrocyte is endowed with these plasticity properties. Differentiating heterogeneous rat glial cells in culture express PA activity. Astroglia were identified as the primary source for the glial PA activity, as no PA activity was detected in the purified oligodendroglia. Cellular PA activity levels of differentiating rat and mouse astroglia are developmentally regulated. The specific activity of PA reached its highest level in rat astroglia at a cell age corresponding to 20-32 postnatal days (P20-P32) and in mouse astroglia at P8-P14; thereafter, this declined (three- to fourfold decrease) within 2 weeks to a low value. At comparable ages (P0-P35), the magnitudes of the PA specific activities of the differentiating rat astroglia and of the developing cerebrum, the tissue from which these cells were purified, were similar. Differentiating rat astroglia produce u-PA and t-PA, the cellular content of both is developmentally regulated, and the u-PA form is only found in the immature cells. u-PA is the predominant form in the immature astrocyte until age P13. Both forms are found in cells at ages P14-P30, and at later stages u-PA disappears while the t-PA type persists as the sole form. After 3 more weeks neither of the PA types was detected. Astroglia express also PA inhibitory activity; the rat astroglial PA inhibitor (PAI) seemed to be identical to PAI-1, one of the known types of PAIs. Stimulation of astroglial proliferation by their subculturing in contrast to Schwann cells did not lead to an increase; rather, beyond a certain cell age (P13) it resulted in a threefold irreversible decline in the PA specific activity of the daughter cells. It has been established that various biochemical properties of CNS mature glia appear on schedule with cell age in culture, thus defining "mature"glia in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Developmental transition in plasticity properties of differentiating astrocytes: age-related biochemical profile of plasminogen activators in astroglial cultures. 214 27

Plasminogen, plasmin, and plasminogen activator (PA) activities and PA and PA inhibitor (PAI) contents were measured in granulosa (GC) and theca interna cell extracts and follicular fluid (FF) obtained from preovulatory follicles of prepubertal gilts treated with eCG and hCG to induce follicular growth and ovulation. Plasmin activity in FF increased just before the time of expected ovulation. This increase was not attributable to changes in plasminogen levels, which remained relatively constant during preovulatory follicular development. The increase in follicular plasmin levels was associated with significant (p less than 0.01) increases in PA activity and content and decreases in PAI content in GC and FF. Western blot analysis suggested that follicular PA activity was represented principally by two forms of tissue type PA (t-PA) each with a pI of 7.8 and with molecular masses of 72,000 and 78,000 daltons, respectively. Two PA-PAI complexes of 126,000 and 130,000 daltons were observed. These complexes were partially dissociated with nucleophilic agents into two t-PA-like forms and a 52,000-dalton PAI protein with a pI of 4.8. Biochemical characteristics of the PAI protein suggest that it belongs to the same class of inhibitors as bovine and human PAI-1. These data indicate that rupture of the porcine ovarian follicle is temporally associated with a net increase in PA activity and an increase in plasmin activity. The increase in PA activity appears to be regulated by changes in PA and PAI content.
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PMID:Changes in and partial identification of the plasminogen activator and plasminogen activator inhibitor systems during ovarian follicular maturation in the pig. 214 59

Components of coagulation and fibrinolysis reactions were identified in situ by immunohistochemical staining in fresh frozen sections of small cell carcinoma of the lung tissue. Tumor cells stained positively for tissue factor, a protein that is capable of activating the extrinsic pathway of coagulation (the components of which have been seen within small cell carcinoma of the lung [SCCL] tissue), and for proteins C and S antigens. Fibrin was seen in a focal distribution at the host-tumor interface, indicating that thrombin had acted upon the fibrinogen found throughout the tumor stroma. Staining with a neoepitope-specific antibody, which does not discriminate between fibrinogen fragment D and fibrin fragment D-dimer, was similar to that of the fibrin antibody. High molecular weight urokinase-type and tissue-type plasminogen activators were seen in vascular endothelium, but neither existed within the tumor. Low molecular weight urokinase was found in rare isolated foci of tumor cells primarily adjacent to areas of necrosis. Plasminogen activator inhibitor-3 occurred in tumor cell cytoplasmic blebs and in necrotic tumor cells, but plasminogen activator inhibitors 1 and 2 were not seen. Our data suggest a mechanism for thrombin generation and fibrin formation within SCCL tissues that could support cell proliferation, stroma formation, and preservation. These features could be conductive to perpetuation of this tumor and conceivably could form the basis of the beneficial effects of antithrombotic therapy seen in SCCL.
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PMID:Abnormal regulation of coagulation/fibrinolysis in small cell carcinoma of the lung. 215 29

The mechanism and incidence of bleeding in patients undergoing fibrinolytic therapy are discussed, the role of laboratory findings in predicting the patient's clinical course is described, and guidelines concerning patient management are presented. Plasminogen activators have more similarities than differences in the mechanisms by which they dissolve thrombi and hemostatic plugs and, therefore, in their potential for vascular reperfusion or bleeding complications. The duration of an active lytic state in the blood varies according to the half-life of the activator; regardless of the agent chosen, however, plasma fibrinogen concentrations do not return to normal levels for one to two days following treatment. If plasminogen activator is still circulating, control of surgical bleeding after plasminogen activator treatment requires correction of the low plasma fibrinogen concentration with cryoprecipitate and administration of antifibrinolytic agents. Tests of coagulation and fibrinolysis can demonstrate a lytic state during therapy, but manipulation of drug therapy based on laboratory results is unlikely to control the patient's clinical course. Safe and effective therapy with plasminogen activators depends more on clinical judgment than on strict interpretation of laboratory test results.
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PMID:Bleeding complications of thrombolytic treatment. 220 51

The purpose of this study was to discover how functional nephrons produce the plasminogen activator as renal function progresses to renal failure. Urine Plasminogen activator (U-PA) activity was measured by the fibrin plate method in 73 patients with various degrees of renal function deterioration from various underlying diseases and in one healthy individual in order to evaluate the plasminogen activator activity of remnant nephrons. The plasminogen activator activity of the 12 consecutive urine samples from the healthy individual showed that is varied according to the time of day, but there was no circadian rhythm. The urine plasminogen activator activity correlated with the osmolality (r = 0.51, P less than 0.001) and creatinine (r = 0.56, P less than 0.001) of the urine, suggesting that it is concentrated at distal nephrons. The fractional sodium excretion rate (FeNa) increased abruptly when GFR decreased below 25 L/day. This pattern was very similar with the relation between total U-PA activity/GFR and GFR. The correlation between total U-PA activity and FeNa was not significant, but there was a significant direct correlation between total U-PA activity/GFR and FeNa (r = 0.775, P less than 0.0001). There was no relationship between the 24-hour urine protein and total U-PA activity or total U-PA activity/GFR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Urinary plasminogen activator activity in progressive renal failure. 227 12

Plasminogen activator activity in normal human tears was found to be 0.03 +/- 0.02 IU/ml with casein plate, and 0.06 +/- 0.04 IU/ml with a spectrophotometric method. Elevated levels of plasminogen activator activity (range 0.11-2.05 IU/ml) were detected in the tear fluid of patients suffering from various corneal and conjunctival diseases including corneal ulcers, superficial keratitis, persistent epithelial defects, recurrent erosions, bullous keratopathy, contact lens associated erosions, alkali burns of the cornea, Mooren's ulcer, conjunctival pemphigoid, acute keratoconus, and corneal melanoma. Plasminogen activator activity, determined in the absence of fibrin in tear samples collected by capillary tubes at low flow rates, is considered to be the result of the presence of urokinase-type plasminogen activator (uPA) deriving from the epithelial cells of the cornea and the conjunctiva. It is suggested that an increase in the level of uPA in tears plays an important role not only in ulceration (the formation and repair of epithelial and stromal defects), but also in the development and healing of a number of other inflammatory processes, infections, immunological processes, chemical burns, contact lens associated lesions; in the invasion of microorganisms and leukocytes, in edema formation, in neovascularization, and in the invasive growth of tumors in the cornea and the conjunctiva.
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PMID:Determination of plasminogen activator activities in normal and pathological human tears. The significance of tear plasminogen activators in the inflammatory and traumatic lesions of the cornea and the conjunctiva. 227 42

Plasminogen activators (PA) and plasminogen activator inhibitors (PAI) have been implicated in the process of extracellular matrix degradation. To study their role in bone matrix turnover, we examined the activity and regulation of PA and PAI in cultures of periosteal osteoblast-like precursor cells and mature osteoblast-like cells from fetal rat calvariae. Both cell populations released PA activity of the tissue type and a 50K PAI species into the culture medium. However, mature osteoblasts had a strikingly lower PA activity and higher PAI activity than periosteal precursor cells, indicating that osteoblast differentiation is associated with a marked decrease in the PA/PAI ratio. PTH and prostaglandin E2 transiently increased PA activity and decreased PAI activity. In contrast, transforming growth factor-beta decreased PA activity and increased PAI activity. Differential effects of these factors on PA and PAI activity may be involved in the regulation of extracellular matrix deposition by osteoblasts.
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PMID:Differential regulation of plasminogen activator and plasminogen activator inhibitor by osteotropic factors in primary cultures of mature osteoblasts and osteoblast precursors. 229 66

Extravascular coagulation and fibrinolysis is an integral part of inflammatory reactions. Disordered expression of procoagulant and profibrinolytic factors by mononuclear phagocytes of the lung (i.e. lung alveolar macrophages (LAM) and interstitial macrophages) may have important bearings on inflammatory lung tissue destruction and repair. Based on this hypothesis we have measured the presence of trigger molecules and activation products of the coagulation and fibrinolytic system in cell-free bronchoalveolar lavage fluid and in bronchoalveolar cells. Patient groups with chronic obstructive disease (COLD) (n = 76), idiopathic pulmonary fibrosis (IPF) (n = 29), sarcoidosis (n = 22), lung cancer (n = 36), pneumonia (n = 39), acquired immunodeficiency syndrome (AIDS) (n = 17) and a control group (n = 60) were studied by bronchoalveolar lavage (BAL). In all patient groups tissue thromboplastin (TPL) and fibrinopeptide A (FPA) were significantly increased compared to controls. Plasminogen activator (PA) activity was significantly lower in patients than in normals, and usually associated with high levels of antifibrinolytic activity. The level of PA inhibitor (PAI-2) was not significantly higher in any patient group compared to controls. The sensitivity of the method for fibrin degradation products (FDP) analysis was not high enough to detect FDP in BAL fluid of control individuals, whereas such products could be demonstrated in 25-53% of patients in various categories. We conclude that disordered expression of procoagulant and plasminogen activator activities in bronchoalveolar lavage fluid may reflect a milieu that favours accumulation of fibrin in inflammatory lung tissue and form the basis for the development of pulmonary fibrosis.
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PMID:Local activation of the coagulation and fibrinolysis systems in lung disease. 238 54


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