UNIPROT:P00750 - FACTA Search

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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 plasmin substrates D-valyl-L-leucyl-lysine-p-nitroanilide (S-2251) and H-D-norleucyl-hexahydrotyrosyl-lysine-p-nitro-anilide (Spectrozyme-PL) on the rate of activation of native human plasminogen in physiological salt solution is studied. Plasminogen activation by two-chain urokinase-type plasminogen activator (urokinase), two-chain tissue-type plasminogen activator (tc-tPA) or trypsin, but not by single chain tPA (sc-tPA) is increased 5- to 10-fold by both substrates, as determined by electrophoretic and spectrophotometric kinetic analysis. The amidolytic activity of sc-tPA, on the other hand, is inhibited by the plasmin substrates in a non-competitive manner (K1 of 6.4 . 10(-4) M for S-2251 and 2.9 . 10(-4) M for Spectrozyme-PL), whereas urokinase and tc-tPA activities are not affected. It is concluded that plasmin substrates containing a lysine residue have a general capacity to enhance plasminogen activation presumably by inducing a conformational change in the native zymogen in a manner similar to 6-aminohexanoate, while the same substrates are inhibitory both on the amidolytic activity of sc-tPA and the activation of native and des1-77-plasminogen by sc-tPA.
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PMID:Dual effect of synthetic plasmin substrates on plasminogen activation. 769 14

In the present study, we have examined the influence of transforming growth factor-alpha (TGF alpha) and FSH in vitro on the granulosa cell plasminogen activator (PA) system accompanying cell proliferation and differentiation during follicular development. Undifferentiated and differentiated rat granulosa cells from diethylstilbestrol (DES)- and eCG-treated immature rats, respectively, were cultured in medium containing FSH (400 ng/ml), TGF alpha (0.5-50 ng/ml), and/or transforming growth factor-beta (TGF beta; 25-100 ng/ml). Net secreted PA (PAs) and cell-associated PA (PAc) activities were higher in differentiated cells and were stimulated by TGF alpha (but not by TGF beta) in a concentration-dependent manner. Basal and FSH-stimulated PAs was higher than PAc and accounted for 70-80% of the total PA activity in both cell preparations. FSH-stimulated PA activities increased in undifferentiated granulosa cells but decreased in differentiated cells with increased duration of culture. A biphasic effect (stimulatory in the first 24 h and inhibitory thereafter) of TGF alpha on FSH-induced PA activities was observed in the cultures of undifferentiated granulosa cells. Whereas both urokinase (uPA) and tissue (tPA) PA appeared to be present in cultures of granulosa cells from DES-treated rats, only tPA could be detected in those from eCG-treated animals. TGF alpha increased basal tPA activity at both stages of follicular development but inhibited activities of uPA in undifferentiated granulosa cells, irrespective of the presence of FSH. This growth factor stimulated basal progesterone (P) and 20 alpha-dihydroprogesterone (20 alpha-OH-P) secretion (an index of granulosa cell differentiation), the effect being more pronounced at the late stage of follicular development.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Follicular stage-dependent regulation of rat granulosa cell plasminogen activator system by transforming growth factor-alpha in vitro. 771 Dec 10

The abortifacient and menstrual effects of the potent antiprogestin, RU 486, are associated with both endometrial hemorrhage and extracellular matrix (ECM) degradation. Such processes reflect reduced perivascular decidual cell hemostatic and increased ECM-degrading protease activity. Therefore, we assessed the effects of RU 486 administration on the expression of immunoreactive (ir) endometrial stromal cell urokinase-type (uPA) and tissue-type (tPA) plasminogen activator and their activities as well as levels of ir type 1 plasminogen activator inhibitor (PAI-1) using a well characterized in vitro model of decidualization. Thus, confluent stromal cell cultures were exposed to vehicle control, 10(-8) mol/L estradiol (E2), 10(-7)-10(-8) mol/L medroxyprogesterone acetate (MPA), E2 plus MPA, or 10(-6)-10(-7) mol/L RU 486 alone or in combination with MPA or E2 plus MPA for 3-4 days. Compared to the vehicle control, E2 and RU 486 used alone had no effect on levels of ir PAI-1, uPA, or tPA or on PA activity in the conditioned medium. In contrast, MPA and E2 plus MPA decreased ir uPA and tPA levels and their corresponding activities, whereas MPA increased, and E2 plus MPA further increased ir PAI-1 release. These effects of progestin were blocked by a log higher concentration of RU 486. Similar results were obtained for steady state PAI-1 messenger ribonucleic acid levels. To determine if RU 486 reversed progestin-inhibited stromal cell uPA and tPA release and progestin-enhanced PAI-1 expression, confluent cultures were exposed to 10(-8) mol/L E2 plus 10(-7) mol/L MPA for 10 days, washed, and reexposed to E2 plus MPA, steroid-free medium, or RU 486 for 3-5 or 9-11 days. Compared with cultures maintained in E2 plus MPA for 3-5 days, withdrawal to a steroid-free medium failed to affect stromal cell ir PAI-1, uPA, or tPA levels. In contrast, exposure to RU 486 for 3-5 days increased ir uPA and tPA levels 5- to 8-fold (P < 0.02) while reducing PAI-1 levels by 85% (P < 0.04). By 9-11 days of treatment, steroid withdrawal and RU 486 exerted similar effects on ir PAI-1, tPA, and uPA levels. Comparable results were obtained for PAI-1, uPA, and tPA steady state messenger ribonucleic acid levels. These findings indicate that RU 486 blocks and reverses progestin-inhibited PA expression, suggesting a mechanism for RU 486-induced endometrial hemorrhage and ECM dissolution.
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PMID:Biological mechanisms underlying the clinical effects of RU 486: modulation of cultured endometrial stromal cell plasminogen activator and plasminogen activator inhibitor expression. 771 76

The purpose of this study is to clarify the effect of burn rabbit serum on the function and structure of endothelial cells in vitro. Morphological study (inverted microscopy, scanning electron microscopy), and determinations of LDH, 6-keto-PGF1 alpha and tissue-type plasminogen activator in the culture medium, changes in the ability of anti-adhesion of platelet to endothelial cells and anti-aggregation property of platelet, etc. were performed. The main results and conclusions were as follows: (1) Rabbit serum obtained in the early stage exerted obvious toxic effects on endothelial cells, functional changes appeared earlier than structural, and in the later changes in intercellular junction and cellular surface appeared earlier; (2) Burn rabbit serum significantly reduced the ability of anti-adhesion of platelet to endothelial cell and anti-aggregation property of platelet, and it might be the primary cause of local micro-thrombosis; (3) Because of the destruction of endothelial surface, the ability of fibrinolysis of endothelial cells was reduced. The activity of tPA might be inhibited b PAI-1, although the content of tPA in the culture medium seemed to be increased after endothelial cell injury.
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PMID:[Endothelial cell injury and changes in anti-coagulation properties induced by burn serum in vitro]. 772 5

Fibrinolysis is dependent upon plasminogen activator (tPA) activity while high fibrinogen levels increase the risk of thromboembolic events. From a cross-sectional population sample of 1558 men and women aged 25 to 64 years, plasma fibrinogen, tPA activity and plasminogen activator inhibitor-1 (PAI) activity were determined using specific assays. Associations with body mass index (BMI), waist-hip ratio (WHR), serum lipids and blood pressure were calculated with uni- and multivariate models where age and smoking were also introduced. In men age, truncal obesity, short height and low HDL cholesterol independently predicted fibrinogen (R2 0.20) while in women obesity per se, total cholesterol, systolic blood pressure, smoking and age were predictors (R2 0.29). tPA activity was negatively associated with BMI and serum triglyceride levels and positively with age in both sexes. In men diastolic blood pressure (R2 0.22) and in women WHR further independently predicted low fibrinolytic activity. HDL was associated with greater fibrinolysis in women (R2 0.15). Relationships with PAI-1 activity were essentially the reverse of tPA but stronger. Prospective interventional studies are needed to answer the question of causality.
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PMID:Fibrinogen and fibrinolytic variables in relation to anthropometry, lipids and blood pressure. The Northern Sweden MONICA Study. 773 Aug 77

The plasminogen activator (PA)-plasmin system is implicated in the degradation of the extracellular matrix in inflammation through activation of metalloproteases and prekallikrein. We examined the activation of the PA-plasmin system in human gingival fibroblast cells (Gin-1 cells) following treatment with lipopolysaccharide (LPS) from Campylobacter rectus, which is frequently detected at sites of periodontal disease. The C. rectus LPS stimulated the plasmin activity in the conditioned medium of Gin-1 cells in a time- and dose-dependent manner, and C. rectus LPS also stimulated the PA activity in the conditioned medium. The PA produced by Gin-1 cells was determined to be urokinase PA (uPA), as preincubation of Gin-1 conditioned medium with anti-uPA antiserum completely inhibited the PA activity while that with anti-tPA antiserum had no inhibitory effect. The concentration of PA inhibitor-1 (PAI-1) in the conditioned medium was decreased by the addition of C. rectus LPS. Therefore, the enhancement of plasmin activity in the conditioned medium was dependent on increased uPA activity via the decrease of the PAI-1 level of Gin-1 cells treated with C. rectus LPS. Furthermore, the conditioned medium of Gin-1 cells treated with C. rectus LPS showed significantly increased kallikrein activity, indicating the conversion of prekallikrein to kallikrein, which converts kininogen into kinin. These findings suggest that C. rectus LPS is a potent stimulator of inflammation of gingival tissue which acts through stimulation of the PA-plasmin system.
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PMID:Effect of Campylobacter rectus LPS on plasminogen activator-plasmin system in human gingival fibroblast cells. 777 54

The objective of the present in vitro study was to examine the potential modulatory influence of tumor necrosis factor-alpha (TNF alpha) on the granulosa cell plasminogen activator (PA) system during follicular development. Undifferentiated and differentiated rat granulosa cells of preantral follicles and antral follicles, respectively, were cultured in a chemically defined medium with or without TNF alpha and in the absence or presence of FSH (400 ng/ml). TNF alpha (0.5-50 ng/ml) inhibited basal and FSH-induced net PA activities in cultures of granulosa cells from preantral and antral follicles in a concentration- and time-dependent manner. Although PA activities with corresponding molecular masses of 55 kDa and 30 kDa (tissue-[tPA] and urokinase-[uPA] type PA, respectively) were observed in culture of undifferentiated granulosa cells, only tPA was detectable in differentiated cells. Concomitant to the stimulation in PA activities by FSH was a marked increase in progestin secretion and a decrease in DNA synthetic capacity at both stages of follicular development. Independent of the differentiative state of the granulosa cells, TNF alpha suppressed FSH-stimulated tPA activity, but potentiated FSH-induced uPA activity in undifferentiated granulosa cells. The inhibition of the gonadotropin action by TNF alpha was accompanied by an increase in PA inhibitor activity, which was more pronounced in cultures of differentiated granulosa cells. TNF alpha inhibited FSH-induced progestin secretion and reversed the action of the gonadotropin on DNA synthesis irrespective of stage of follicular maturation. These studies demonstrate that TNF alpha modulates gonadotropic action on granulosa cell differentiation (PA and progestin secretion) and proliferation (DNA synthesis) during follicular development.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor necrosis factor alpha inhibits rat granulosa cell plasminogen activator activity in vitro during follicular development. 777 96

Forty-nine bacterial strains representing five species known to interact with human plasminogen were tested for the ability to bind the two major human plasminogen activators, t-PA and urokinase. The bacterial species tested included Haemophilus influenzae, Neisseria meningitidis, Streptococcus pyogenes, Streptococcus equisimilis and human group G streptococci. All N. meningitidis and 11 of 14 H. influenzae strains displayed substantial binding of t-PA with values in the range of 20-46%. On the contrary, none of the streptococcal strains bound significant amounts of tPA. With urokinase no binding could be found for any of the bacterial species tested. Scatchard analysis with a selected H. influenzae strain (HI23354) demonstrated 10,000 receptors per bacterium for t-PA with a Kd value of about 20 nmol l-1. The corresponding values with a selected N. meningitidis strain (Mo 52) was 8500 receptors per bacterium and 70 nmol l-1. t-PA binding could be reduced about 40% by the addition of 10 mmol l-1 of the lysine analogue epsilon-aminocaproic acd (EACA) whereas no inhibitory effect could be demonstrated with arginine. Addition of 2 mumol l-1 of plasminogen which is enough to occupy all bacterial sites for plasminogen did not interfere with the t-PA binding, suggesting that the receptors for t-PA and plasminogen are distinct. Using very high plasminogen concentrations however, t-PA binding could be reduced by about 50% possibly due to an interaction between t-PA and plasminogen in the fluid phase. Our results demonstrate the occurrence of a previously unknown type of bacterial receptor that is capable of specifically binding t-PA.
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PMID:Binding of tissue-type plasminogen activator (t-PA) to Neisseria meningitidis and Haemophilus influenzae. 780 68

A mutant recombinant plasminogen activator inhibitor 1 (PAI-1) was created (Ser-338-->Cys) in which cysteine was placed at the P9 position of the reactive center loop. Labeling this mutant with N,N'-dimethyl-N-(acetyl)-N'-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) ethylene diamine (NBD) provided a molecule with a fluorescent probe at that position. The NBD-labeled mutant was almost as reactive as wild type but was considerably more stable. Complex formation with tissue or urokinase type plasminogen activator (tPA or uPA), and cleavage between P3 and P4 with a catalytic concentration of elastase, all resulted in identical 13-nm blue shifts of the peak fluorescence emission wavelength and 6.2-fold fluorescence enhancements. Formation of latent PAI showed the same 13-nm spectral shift with a 6.7-fold fluorescence emission increase, indicating that the NBD probe is in a slightly more hydrophobic milieu. These changes can be attributed to insertion of the reactive center loop into the beta sheet A of the inhibitor in a manner that exposes the NBD probe to a more hydrophobic milieu. The rate of loop insertion due to tPA complexation was followed using stopped flow fluorimetry. This rate showed a hyperbolic dependence on tPA concentration, with a half-saturation concentration of 0.96 microM and a maximum rate constant of 3.4 s-1. These results demonstrate experimentally that complexation with proteases is presumably associated with loop insertion. The identical fluorescence changes obtained with tPa.PAI-1 and uPA.PAI-1 complexes and elastase-cleaved PAI-1 strongly suggest that in the stable protease-PAI-1 complex the reactive center loop is cleaved and inserted into beta sheet A and that this process is central to the inhibition mechanism.
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PMID:A fluorescent probe study of plasminogen activator inhibitor-1. Evidence for reactive center loop insertion and its role in the inhibitory mechanism. 789 Jun 53

Keratinocytes propagated in low calcium (30 microM CaCl2) serum-free media grow in a monolayer and exhibit morphologic and biosynthetic phenotypes most similar to those of keratinocytes in the basal layer of the normal epidermis. When the calcium in the media is elevated to 1 mM, the cells stratify and differentiate. The effects of calcium on human foreskin keratinocyte expression of urokinase type (uPA) and tissue type (tPA) plasminogen activator enzymes and plasminogen activator inhibitor 1 and 2 (PAI-1, PAI-2) were assessed by Northern analyses. Our data show that keratinocytes, cultured in the presence of low and high CaCl2 concentrations, express transcripts for uPA and PAI-2. Message levels for uPA were dramatically reduced in cultures stimulated with calcium, whereas those for PAI-2 were only slightly decreased. Little PAI-1 mRNA and no tPA mRNA were detected, independent of calcium levels. Actin mRNA levels were not modulated consequent to calcium stimulation. Hybridizations to 28S ribosomal RNA confirmed that equal amounts of RNA were analyzed from cells grown under low and high calcium conditions. These data demonstrate that keratinocytes, propagated in serum-free media under low and high calcium conditions, are similar to normal human epidermis with respect to their expression of regulators of plasminogen activation. Additionally, they suggest that the ratio of PAI-2 to uPA increases with keratinocyte differentiation.
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PMID:Calcium modulates the expression of urokinase plasminogen activator and plasminogen activator inhibitor 2 by human keratinocytes. 792 56

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