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

---

Query: EC:3.4.21.7 (plasmin)
9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
...
PMID:Fibrin and plasminogen structures essential to stimulation of plasmin formation by tissue-type plasminogen activator. 293 32

The effect of heating on plasmin activity in various media, including phosphate buffer pH 7.0, skim milk, blood plasma, solutions of casein and solutions of whey proteins were investigated. Plots of log residual activity v. heating time were linear at all temperatures from 63 to 143 degrees C. In buffer solutions the presence of casein led to substantial substrate protection, the Arrhenius plots being linear both in the presence and absence of casein. The activation energy, Ea, for the inactivation reaction, was 62.4 kJ/mol in buffer alone and 58.4 kJ/mol with casein present at 25 mg/ml. In skim milk, despite the presence of casein at a similar concentration, plasmin was no more stable to heat than in buffer alone, and a curved Arrhenius plot was obtained indicating a more complex inactivation mechanism. Heating in the presence of proteins having free -SH groups accelerated the inactivation of plasmin. The role of -SH groups was confirmed by experiments with added alpha-lactalbumin, in which no free -SH groups occur, and reduced carboxymethylated beta-lactoglobulin, both of which were without effect. In blood plasma, plasmin was less stable to heat than in buffer (pH 7.0) or in skim milk. Plasminogen behaved very similarly to plasmin either when activated to plasmin with urokinase before heating or when activated afterwards. A hypothesis is presented to describe the heat inactivation and denaturation of plasmin. Technologically important findings are that in skim milk plasmin was largely unaffected by pasteurization conditions and 30-40% of its activity remained even after ultra high temperature processing conditions.
...
PMID:Heat stability of plasmin (milk proteinase) and plasminogen. 294 65

Fourteen patients with deep venous thrombosis (DVT) and a positive 99mTc-plasmin test were followed up to determine how soon a negative test was obtained. Localization and extension of the thrombi were determined by phlebography. Plasminogen activator activity in vein walls and local fibrinolytic activity after venous occlusion were measured in order to find out what the prerequisites for impaired thrombolysis are. The time required to obtain a negative 99mTc-plasmin test showed considerable variation, ranging from less than 1 week to more than 6 months. The 99mTc-plasmin test had returned to normal in 64% of the patients after 6 months. No relationship was found between vessel wall fibrinolysis and time to normalization. Instead, we found an association between the time to normalization of the 99mTc-plasmin test and the size of the thrombus, according to phlebography, as well as between the time to normalization of the 99mTc-plasmin test and the extension of leg points with a positive 99mTc-plasmin test at admission. The finding of abnormal 99mTc-plasmin test results more than 6 months after acute DVT is of practical importance and warrants caution when evaluating patients with symptoms and signs suggestive of acute recurrent DVT.
...
PMID:Return to normal of 99mTc-plasmin test after deep venous thrombosis and its relationship to vessel wall fibrinolysis. 294 23

The effect of subclinical mastitis on levels of plasminogen and plasmin in milk from cows in a high-yielding herd was investigated. Comparisons were made with levels of milk Na, antitrypsin and N-acetyl-beta-D-glucosaminidase (NAGase). In samples from mastitic quarters plasminogen activity, as measured after activation to plasmin, increased by only 21% and plasmin by 82%, while NAGase increased by 307%. Plasminogen was the only component that was normally distributed, all other components showed more or less skewed distributions. Plasmin and plasminogen were significantly related to the other components. However, plasminogen plateaued when the other components continued to increase. There was thus no further increase in plasminogen with the severity of inflammation as with the other components. Plasmin showed a similar although less pronounced tendency. Results of treatment of mastitic whey samples with acid suggested that the non-linear increase in plasmin activity was due to interaction with acid-labile proteinase inhibitors. Mastitis led to dissociation of plasminogen and plasmin from the casein micelles. The degree of activation of plasminogen was higher with casein-associated than with soluble plasminogen in both healthy and mastitic milks. Plasmin was very closely related to milk Na, which is a sensitive indicator of epithelial integrity. It is suggested that plasmin contributes to Na leakage into milk by degrading membrane proteins of the epithelial lining. Plasminogen and antitrypsin, which are both plasma proteins, were not identically affected by stage of lactation, indicating nonidentical modes of transport from plasma to milk.
...
PMID:Effect of subclinical mastitis on milk plasminogen and plasmin compared with that on sodium, antitrypsin and N-acetyl-beta-D-glucosaminidase. 294 39

Activation of the plasma zymogen plasminogen to the enzyme plasmin by the early bovine embryo was evaluated. Sixteen-cell embryos to early morulae were collected at death from handmated synchronized and superovulated crossbred beef cows. Embryos were cultured in Ham's F-12 medium supplemented with 15 mg/ml bovine serum albumin containing 0, 15, 30, 60 or 120 micrograms/ml plasminogen in a humidified atmosphere of 5% CO2 in air at 37 degrees C. Cultures were observed every day, and stage of development was recorded. Medium was collected at 24-h intervals, starting at initiation and continuing through 288 h of culture. Plasminogen activator and plasmin levels in the culture media were determined, using a caseinolytic assay. The percentages of embryos developing to the initiating hatching blastocyst, hatched blastocyst, attached blastocyst, and attached blastocyst with trophoblastic outgrowth stages were not significantly different between the five levels of plasminogen. Initiation and completion of hatching, however, accelerated as plasminogen concentration increased in the culture media. Plasminogen activator production, expressed as milliunits X ml-1 X h-1 X viable embryo-1, was low for the first 48 h of culture, increased between 48-120 h, and tended to plateau thereafter. Plasminogen activation, measured indirectly as the plasmin concentration in a microdrop of medium and expressed as microgram plasmin X ml-1 X h-1 X viable embryo-1, followed plasminogen activator production, and was consistently low for the first 48-72 h of culture. Embryonic activation of plasminogen increased sharply thereafter, and also plateaued after 120 h.
...
PMID:Activation of plasminogen by the early bovine embryo. 295 97

Addition of human plasminogen to three different pemphigus plasma samples showed a synergistic effect on acantholysis in the skin organ culture model. Human plasmin itself, without addition of pemphigus plasma, induced typical acantholytic changes in the skin explants, causing different types of acantholysis in a dose- and time-dependent manner: in the presence of 3 CU plasmin per ml culture medium, focal suprabasilar acantholysis of pemphigus vulgaris type could be detected after 72 h incubation, whereas 15 CU/ml caused extended acantholysis of pemphigus foliaceus type in the upper epidermal layers after 24 h, and extended acantholysis of benign chronic pemphigus (Hailey-Hailey disease) type comprising all layers of the epidermis after 48 h incubation. Plasminogen activator levels (Mr 55,000 urokinase type) in tissue extracts of skin explants and in culture media were reduced after 24 and 48 h incubation with pemphigus IgG as compared to control experiments with normal human IgG; this probably resulted from urokinase inactivation by reaction with inhibitors. These results lend support to the hypothesis proposed by Hashimoto et al. in 1983 that the plasminogen activator-plasmin system could play an essential role in the protease mechanisms of pemphigus acantholysis.
...
PMID:Plasmin induces acantholysis in skin organ cultures. 295 65

Tissue plasminogen activator (t-PA) and/or pro-urokinase (pro-UK) induced lysis of standard 125I-fibrin clots suspended in plasma was studied. Doses were kept below the concentration at which a nonspecific effect was seen, i.e., where fibrinogenolysis and major plasminogen consumption were observed. Small amounts of t-PA potentiated clot lysis by pro-UK by attenuating the lag phase characteristic of pro-UK, and causing a much earlier transition to the rapid phase of lysis. Similar promotion of the fibrinolytic effect of pro-UK was obtained when clots were pretreated with UK or with a little plasmin (less than 1% clot lysis). Promotion by plasmin was nullified by a subsequent treatment of the clot with carboxypeptidase B, indicating that the plasmin effect was related to the exposure of carboxy terminal lysine residues on fibrin. These lysine termini, absent in undegraded fibrin, are known to be essential for the high affinity binding of plasminogen to fibrin. In contrast, clot lysis by t-PA was unaffected by plasmin pretreatment and little affected by carboxypeptidase B treatment of the fibrin substrate. Therefore, plasminogen bound to lysine termini on fibrin, although found to be essential for pro-UK, did not appear to serve as a substrate for t-PA. Selective activation of fibrin bound plasminogen has been attributed to the conformational change in Glu-plasminogen that occurs as a result of binding. The present findings suggest that this conformational change occurs when plasminogen is bound to a terminal lysine but not to an internal lysine. Plasminogen bound to the latter site on fibrin was activated by t-PA and therefore is involved in the ternary complex. This initiates lysis of the undegraded clot and exposes the plasminogen binding sites required by pro-UK. By their complementary activation of fibrin bound plasminogen, t-PA followed by pro-UK induces efficient and synergistic fibrinolysis, whereas each is relatively inefficient when used alone.
...
PMID:Complementary modes of action of tissue-type plasminogen activator and pro-urokinase by which their synergistic effect on clot lysis may be explained. 296 31

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.
...
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

Marked changes of the plasminogen activator activity, plasmin inhibition, and plasminogen activator inhibition were found in fatty streaks and fibrous plaques compared to the normal intima of the human aorta. Plasminogen activator activity and plasmin inhibition showed the following pattern: fibrous plaques greater than fatty streaks greater than normal intima. Plasminogen activator inhibition showed the opposite pattern: normal intima greater than fatty streaks greater than fibrous plaques. The tissue-type, but not the urokinase-type, plasminogen activator was detected immunologically.
...
PMID:Fatty streaks and fibrous plaques in human aorta show increased plasminogen activator activity. 297 93

Single-chain urokinase-like plasminogen activators have been determined by an indirect method (after activation to urokinase by plasmin and chromogenic assay with S 2444) in the cytosol of a rat tumor model. Variants of the R 3230 AC rat mammary adenocarcinoma were studied, including a subline with increased metastatic potential established by lung colony assay. The cellular content of the UK precursor was found to be significantly higher in the metastatic variant. Plasminogen activator-mediated invasion and collagenolysis of cells with the metastatic phenotype may be regulated by the release of the precursor which lacks reactivity with inhibitors, its transient activation and subsequent inhibition of the urokinase formed.
...
PMID:Single-chain, urokinase-type plasminogen activator in a tumor model linked to metastatic potential. 297 33


<< Previous 1 2 3 4 5 6 7 8 9 10

---