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)

Plasmin can degrade fibronectin and laminin, two important components of the extracellular matrix facilitating cell sliding and healing following a wound. In this study we investigated the relationship between the tear fluid level of plasmin and plasminogen activator and the healing of a corneal wound. Anterior keratectomy (AKE) was performed for seven rabbits (11 eyes). Eight eyes were rewounded after re-epithelialization. Tear fluid samples were collected with capillaries before wounding and during wound healing. Plasmin and plasminogen activator (PA) activities were determined using radial caseinolysis procedures. After AKE the plasmin concentrations increased rapidly, from a mean (+/- SEM) of 3.9 +/- 0.9 micrograms/ml to a mean of 37.9 +/- 7.8 micrograms/ml (p less than 0.01), and decreased during wound healing. Rewounding also resulted in an increase in plasmin concentration in the tear fluid (from a mean of 2.9 +/- 0.6 micrograms/ml to a mean of 5.0 +/- 1.1 micrograms/ml; p greater than 0.05). The PA activity showed an inverse trend as it decreased after AKE from a mean of 2.0 +/- 0.6 IU/ml to a mean of 0.3 +/- 0.1 IU/ml (p less than 0.001). During wound healing and re-epithelialization, the PA activity increased again, to 2.1 +/- 0.3 IU/ml (p less than 0.001). Abrasion of the newly grown epithelium in eight eyes caused a second elevation of PA activity which was not significant. This study demonstrates a close association between the healing of corneal wounds and changes in the plasmin and PA activities in tear fluid. Determination of the activity of these enzymes may therefore be useful for monitoring corneal wound healing.
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PMID:Plasmin and plasminogen activator activities in tear fluid during corneal wound healing after anterior keratectomy. 253 68

The sequence of ovarian events during the process of ovulation discussed in this review is schematically represented in Figure 1. It is obvious that LH, perhaps with some contribution from FSH, is the normal physiological trigger for the ovulatory sequence of events and it appears from the available information that LH's effects are mainly mediated via adenylate cyclase and increased cAMP. The cAMP in turn, via cAMP-dependent protein kinase, influences at least three distinct steps in the ovulatory process which seem to be of crucial importance, namely 1) the stimulation of steroidogenesis; 2) the stimulation of cyclooxygenase/lipooxygenase leading to increased prostaglandin/leukotriene synthesis; and 3) the stimulation of plasminogen activator which catalyzes the conversion of plasminogen to plasmin. A fourth crucial step in the ovulatory mechanism is the LH-induced increase in latent collagenase, but it remains to be determined if this step is mediated via cAMP. Concomitant with the increase in latent collagenase, there also appears to be an LH-dependent increase in collagenase inhibitors. The latent collagenase is then activated and it appears that leukotrienes and prostaglandins as well as plasmin may be involved in this process. The active collagenase causes a digestion of the collagen in the follicle wall. Plasmin as well as possibly other proteolytic enzymes such as proteoglycanases (Too et al., 1984) may cause a further dissociation of the follicular wall. These processes of digestion of collagen and dissociation of the collagen fibers result in an opening in the follicular wall with the formation of the stigma and rupture. While the weakening of the follicular wall takes place throughout the entire wall, rupture remains for the most part a localized process at the apex of the follicle. This localization of the rupture may be explained on the basis of mechanical factors operating when the follicle wall thins and weakens (Rodbard, 1984). While it is clear that prostaglandins and leukotrienes can influence smooth muscle by causing contractions and that these compounds can cause vascular changes such as increased permeability, vasodilatation and vasoconstriction, it is not clear what the exact role of these latter processes are in ovulation. It appears that progesterone and not estrogen play an important role in the mechanism of LH induced follicular rupture, but the locus of action of progesterone and its mechanism of action remains to be determined.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanism of mammalian ovulation. 265 83

Plasminogen activation catalysed by tissue-type plasminogen activator (t-PA) has been examined in the course of concomitant fibrin formation and degradation. Plasmin generation has been measured by the spectrophotometric method of Petersen et al. (Biochem. J. 225 (1985) 149-158), modified so as to allow for light scattering caused by polymerized fibrin. Glu1-, Lys77- and Val442-plasminogen are activated in the presence of fibrinogen, des A- and des AB-fibrin and the rate of plasmin formation is found to be greatly enhanced by both des A- and des AB-fibrin polymer. Plasmin formation from Glu1- and Lys77-plasminogen yields a sigmoidal curve, whereas a linear increase is obtained with Val442-plasminogen. The rate of plasmin formation from Glu1- and Lys77-plasminogen declines in parallel with decreasing turbidity of the fibrin polymer effector. In order to study the effect of polymerization, this has been inhibited by the synthetic polymerization site analogue Gly-Pro-Arg-Pro, by fibrinogen fragment D1 or by prior methylene blue-dependent photooxidation of the fibrinogen used. Inhibition of polymerization by Gly-Pro-Arg-Pro reduces plasmin generation to the low rate observed in the presence of fibrinogen. Antipolymerization with fragment D1 or photooxidation has the same effect on Glu1-plasminogen activation, but only partially reduces and delays the stimulatory effect on Lys77- and Val442-plasminogen activation. The results suggest that protofibril formation (and probably also gelation) of fibrin following fibrinopeptide release is essential to its stimulatory effect. The gradual increase and subsequent decline in the rate of plasmin formation from Glu1- or Lys77-plasminogen during fibrinolysis may be explained by sequential exposure, modification and destruction of different t-PA and plasminogen binding sites in fibrin polymer.
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PMID:Fibrin and plasminogen structures essential to stimulation of plasmin formation by tissue-type plasminogen activator. 293 32

Plasmin is a labile enzyme destroyed by a process termed autodigestion. Studied by a kinetic assay on the substrate Tos-Gly-Pro-Lys-pNA this process is shown to follow a bimolecular mode of reaction, which is retarded by plasmin degradation products. Plasmin is protected by fibrinogen, by epsilon-aminocaproic acid (6-aminohexanoic acid), by increasing ionic strength, and by glycerol. CNBr fragments of fibrinogen did not protect. Lack of substrate protection of plasmin may give rise to errors in a two-stage plasminogen activator assay, while the presence of substrate in a one-stage method prevents degradation of the generated plasmin.
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PMID:The autodigestion of human plasmin follows a bimolecular mode of reaction subject to product inhibition. 293 86

Trinitrobenzyl alkylation of poly(D-lysine) provides a novel powerful stimulator of tissue-type plasminogen activator. Its stimulatory effect on plasminogen activation is far greater than that of the original poly(D-lysine), and even surpasses that of fibrin. Its effect on plasmin-catalysed modification of both tissue-type plasminogen activator (t-PA) and native (Glu-1-) plasminogen are also investigated. Cleavage of one-chain t-PA to its two-chain form is monitored by measuring the increase in amidolytic activity which accompanies this transformation. Presupposing apparent first-order reaction kinetics, a theory is developed by which the rate constant, kcat/Km = 1.0 X 10(6) M-1 X s-1 of plasmin cleavage of one-chain t-PA can be calculated. Plasmin-catalysed transformation of 125I-labelled Glu-1- to Lys-77-plasminogen is quantified following separation by polyacrylamide gel electrophoresis at pH 3.2. A rate constant, kcat/Km = 4.4 X 10(3) M-1 X s-1 is obtained for the reaction between plasmin and Glu-1-plasminogen in the presence of 1 mM trans-4-(aminomethyl)cyclohexane-1-carboxylic acid. Both of the above plasmin-catalysed reactions are strongly enhanced by trinitrobenzoylated poly(D-lysine). The mechanism of action of this stimulator is elucidated by studying its binding to both activator and plasmin(ogen), and by direct comparison of the results with measurements of plasminogen activation kinetics in the presence of the stimulator. Binding studies are performed exploiting the observation that an insoluble yellow complex is formed between plasminogen and modified poly(D-lysine). Protein-polymer interactions are also studied with solubilised components in an aqueous two-phase partition system containing dextran and poly(ethylene glycol). The rate enhancement of plasminogen activation is found to be closely correlated to the association of plasminogen to the stimulator. It is proposed that the stimulator effects of this simple polymer on the enzymatic activities of both plasminogen activator and plasmin are brought about by association of the proteinase and its substrate to a common matrix. Similarities between the action of the artificial and the natural stimulator (fibrin) are stressed. These properties of trinitrobenzoylated poly(D-lysine) makes it useful as a model for the study of the regulatory mechanism of the fibrinolytic process at the molecular level.
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PMID:Trinitrobenzoylated poly(D-lysine) as a stimulator of interactions between plasminogen, plasmin, and tissue-type plasminogen activator. 294 20

Exercise to exhaustion was associated with the appearance in plasma of plasminogen activator (PA) in several mol wt forms, as identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with zymography. A number of active bands, all immunologically identified as tissue-type PA (t-PA), were observed. The major form had an apparent mol wt of approximately 60,000 and is due to free t-PA. The other strong bands had apparent mol wts of approximately 110,000 and 180,000. The 110,000 band, also present in pre-exercise samples, represents t-PA complexed with its major inhibitor (PAI-1), and the 180,000 band is due to t-PA complexed with C1 inhibitor. The released forms of t-PA were cleared rapidly after cessation of exercise at exhaustion. Urokinase-type PA (u-PA) activity was also identified in pre- and postexercise samples at an apparent mol wt of approximately 50,000. This is consistent with its being free u-PA; no complexed forms of u-PA were observed. Qualitatively similar changes in plasma PA were observed after venous occlusion. Small quantities of plasmin were generated after strenuous exercise, as observed by detection of plasmin-alpha 2-antiplasmin complex by two-dimensional immunoelectrophoresis in three of five subjects. This complex was cleared rapidly after cessation of exercise. Plasmin-alpha 2-antiplasmin complex was not detected in any of the subjects after venous occlusion.
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PMID:Plasminogen activator in normal subjects after exercise and venous occlusion: t-PA circulates as complexes with C1-inhibitor and PAI-1. 295 96

The fibrinolytic enzyme system of menstrual and peripheral blood was studied in three groups of women: Group 1, 20 subjects (mean age 37.2 years) with normal menstrual loss; Group 2, 20 patients (mean age 39 years) with dysfunctional uterine bleeding studied before treatment, and Group 3, during treatment with a fibrinolytic inhibitor, tranexamic acid (AMCA) (1 g 8-hourly). The fibrinolytic activity (plasminogen activator and plasmin) of menstrual blood was significantly higher than that of peripheral blood in the three groups (p less than 0.001). Both plasminogen activator and plasmin were higher in the menstrual blood of patients with menorrhagia (Group 2) compared with the control subjects (Group 1) (p less than 0.001 and p less than 0.1 respectively). Treatment with AMCA significantly reduced both plasminogen activator (p less than 0.01) and plasmin (p less than 0.05) in the menstrual blood of patients with menorrhagia (Group 3). No significant differences in fibrinolytic activity were found in peripheral blood between Groups 1 and 2; however, both plasminogen activator and plasmin were significantly lower (p less than 0.01) in Group 3 than in Group 2. Plasmin activity was also significantly lower (p less than 0.05) in Group 3 compared to Group 1. These findings confirm the presence of increased fibrinolytic activity in the uterus in excessive (dysfunctional) bleeding.
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PMID:The fibrinolytic enzyme system in normal menstruation and excessive uterine bleeding and the effect of tranexamic acid. 295 34

Tissue-type plasminogen activator (t-PA) is a serine protease with a molecular weight of about 70,000. It activates plasminogen to plasmin by cleavage of the Arg 560-Val 561 peptide bond. Kinetic analysis showed that the activation obeys Michaelis-Menten kinetics and that the presence of fibrin strikingly enhances the activation rate. The directed action of plasmin towards fibrin in vivo can be explained by the low Michaelis constant in the presence of fibrin (0.16 microM) which allows efficient plasminogen activation on a fibrin clot, while its high value in the absence of fibrin (65 microM) prevents efficient activation in plasma. Plasmin formed on the fibrin surface is protected from rapid inactivation by alpha 2-antiplasmin. Studies on the thrombolytic properties of t-PA (purified from melanoma cell cultures or obtained by recombinant DNA technology) in various animal models and in selected patients revealed that t-PA is a specific thrombolytic agent which induces thrombolysis without causing extensive systemic activation of the fibrinolytic system.
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PMID:Tissue-type plasminogen activator. 295 11

Plasminogen activation by tissue-type plasminogen activator (t-PA) is stimulated by fibrin. In a purified system maximal fibrin-enhanced plasmin formation occurs with a delay after an initial phase of slow plasmin formation (lag phase). In the present study purified stimulating CNBr-fragment FCB-2 of fibrinogen was used, and kinetics of plasminogen activation by t-PA were analyzed with respect to the lag phase. At constant FCB-2 concentration the duration of the lag phase decreased with increasing concentrations of t-PA and plasminogen. During this period the rate of plasmin formation/min increased linearly with time with a slope dependent on the initial concentrations of FCB-2, plasminogen, and t-PA. Plasmin pretreatment of FCB-2 resulted in a dose- and time-dependent shortening of the lag phase, and at plasmin concentrations greater than or equal to 1 nM and preincubation times greater than or equal to 3 min maximal plasmin formation occurred without a lag phase. Kinetics during the phase of maximal and constant plasmin formation were not influenced by plasmin pretreatment of FCB-2. We therefore conclude that maximal t-PA-dependent plasmin formation in a system stimulated by purified FCB-2 requires plasmin modification of FCB-2.
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PMID:Plasminogen activation by tissue plasminogen activator in the presence of stimulating CNBr fragment FCB-2 of fibrinogen is a two-phase reaction. Kinetic analysis of the initial phase of slow plasmin formation. 296 2

Platelets were found to provide a surface for activation of plasminogen by the tissue-type plasminogen activator (t-PA) at an optimum concentration and to potentiate the generation of plasmin by the amidolytic method, fibrin lysis time and fibrin plate method. The effect of platelets on amidolytic activity on S-2251 was due to the potentiating effect of plasminogen activation by t-PA, because it was observed only in the presence of both plasminogen and t-PA. Plasmin generation was also evidenced in the SDS-PAGE profile of the supernatant from a mixture containing t-PA and plasminogen with platelets. These findings suggests that the potentiating activity of platelets on plasminogen activation by t-PA in circulation is one of the causes of fibrinogenolysis during fibrinolytic therapy with a high dose of t-PA. Platelets from patients with various diseases showed different potentiating activity on plasminogen activation by t-PA. The assay of this ability of platelets may be a new tool for evaluating their role in the blood fibrinolytic process.
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PMID:Plasminogen activation by tissue plasminogen activator in the presence of platelets. 297 48


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