-
Nature Oct 1958
Topics: Biochemical Phenomena; Cartilage; Chondroitin Sulfates; Fibrinolysin; Humans
PubMed: 13590186
DOI: 10.1038/182948a0 -
The American Journal of Physiology Sep 1960
Topics: Antifibrinolytic Agents; Endopeptidases; Fibrinolysin; Hydrolases; Peptide Hydrolases; Thrombolytic Therapy; alpha-2-Antiplasmin
PubMed: 13682944
DOI: 10.1152/ajplegacy.1960.199.3.491 -
Nouvelle Revue Francaise D'hematologie 1965
Review
Topics: Fibrinogen; Fibrinolysin; Humans; Immunoelectrophoresis
PubMed: 14307707
DOI: No ID Found -
Biology of Reproduction Apr 2012Until recently, the role of the proteolytic system involving serine proteases in follicle rupture during ovulation in mammalian species has been a subject of...
Until recently, the role of the proteolytic system involving serine proteases in follicle rupture during ovulation in mammalian species has been a subject of controversy. We undertook the present study to examine whether proteases play a role in follicle rupture using the teleost medaka (Oryzias latipes) model. Various serine protease inhibitors, including a specific plasmin inhibitor, drastically reduced the rate of ovulation, as assessed by an in vitro ovulation assay, which was established for the fish. Biochemical, molecular biological, and immunological analyses demonstrated that plasminogen/plasmin was present in large follicles destined to ovulate. The active protease, plasmin, was detected in follicles approximately 3-7 h before the expected time of ovulation. Specific antibodies against the medaka plasmin light chain suppressed the ovulation rate of the follicles when antibodies were added to the medium during the period in which active plasmin was generated. This finding was an indication that a plasmin-like protease similar if not identical to plasmin plays a role in follicle rupture during ovulation in the medaka. Our data also indicate that this serine protease participates in the rupture for only a few hours prior to the activation of matrix metalloproteinase (Mmp)-mediated hydrolysis at ovulation. Based on our previous and current data, we propose a follicle rupture model involving two different proteolytic enzyme systems, serine protease and Mmp, in medaka ovulation. The current study is the first to provide evidence of the indispensable role of plasmin or a plasmin-like protease in the ovulation of a nonmammalian vertebrate species.
Topics: Animals; Female; Fibrinolysin; Oryzias; Ovarian Follicle; Ovulation; Plasminogen; Serine Proteinase Inhibitors
PubMed: 22278979
DOI: 10.1095/biolreprod.111.093880 -
Journal of Chemical Information and... Jul 2017Inhibition of plasmin has been found to effectively reduce fibrinolysis and to avoid hemorrhage. This can be achieved by addressing its kringle 1 domain with the known...
Inhibition of plasmin has been found to effectively reduce fibrinolysis and to avoid hemorrhage. This can be achieved by addressing its kringle 1 domain with the known drug and lysine analogue tranexamic acid. Guided by shape similarities toward a previously discovered lead compound, 5-(4-piperidyl)isoxazol-3-ol, a set of 16 structurally similar compounds was assembled and investigated. Successfully, in vitro measurements revealed one compound, 5-(4-piperidyl)isothiazol-3-ol, superior in potency compared to the initial lead. Furthermore, a strikingly high correlation (R = 0.93) between anti-fibrinolytic activity and kringle 1 binding affinity provided strong support for the hypothesized inhibition mechanism, as well as revealing opportunities to fine-tune biological effects through minor structural modifications. Several different ligand-based (Freeform, shape, and electrostatic-based similarities) and structure-based methods (e.g., Posit, MM/GBSA, FEP+) were used to retrospectively predict the binding affinities. A combined method, molecular alignment using Posit and scoring with T, lead to the highest coefficient of determination (R = 0.6).
Topics: Antifibrinolytic Agents; Drug Discovery; Fibrinolysin; Isoxazoles; Molecular Docking Simulation; Piperidines; Protein Domains; Quantitative Structure-Activity Relationship; Thermodynamics
PubMed: 28653850
DOI: 10.1021/acs.jcim.7b00255 -
International Journal of Biological... Apr 2012Mechanisms of homocysteine (Hcy) contribution to thrombosis are complex and only partly recognized. The available data suggest that the prothrombotic activity of...
Mechanisms of homocysteine (Hcy) contribution to thrombosis are complex and only partly recognized. The available data suggest that the prothrombotic activity of homocysteine may be not only a result of the changes in coagulation process and endothelial dysfunction, but also the dysfunction of fibrinolysis. The aim of the present work was to assess the effects of homocysteine (10-100 μM mM) and its thiolactone (HTL, 0.1-1 μM) on plasminogen and plasmin functions in vitro. The amidolytic activity of generated plasmin in Hcy or HTL-treated plasminogen and plasma samples was measured by the hydrolysis of chromogenic substrate. Effects of Hcy and HTL on proteolytic activity of plasmin were monitored electrophoretically, by using of fibrinogen as a substrate. The exposure of human plasma and purified plasminogen to Hcy or HTL resulted in the decrease of urokinase-induced plasmin activity. In plasminogen samples treated with the highest concentration of homocysteine (100 μM) or thiolactone (1 μM), the activity of plasmin was inhibited by about 50%. In plasma samples, a reduction of amidolytic activity by about 30% (for 100 μM Hcy) and 40% (for 1 μM HTL), was observed. Both Hcy and HTL were also able to diminish the streptokinase-induced proteolytic activity of plasmin. In conclusion, the results obtained in this study demonstrate that Hcy and HTL may affect fibrinolytic properties of plasminogen and plasma, leading to the decrease of plasmin activity.
Topics: Adult; Animals; Fibrinolysin; Homocysteine; Humans; Hydrolysis; Plasminogen; Proteolysis; Streptokinase; Urokinase-Type Plasminogen Activator; Young Adult
PubMed: 22197896
DOI: 10.1016/j.ijbiomac.2011.12.002 -
Thrombosis and Haemostasis Oct 2010We previously demonstrated a significant margin of haemostatic safety for full-length plasmin in comparison with tissue plasminogen activator (t-PA). We now report... (Comparative Study)
Comparative Study
We previously demonstrated a significant margin of haemostatic safety for full-length plasmin in comparison with tissue plasminogen activator (t-PA). We now report studies that compare haemostatic safety of full-length plasmin with a novel recombinant plasmin derivative, (Δ K2-5) plasmin, consisting of kringle 1 linked to the serine protease domain of plasmin. Agent was administered intravenously in a randomised, blinded manner in a rabbit model of fibrinolytic haemorrhage. A dose-related decrease in α2-antiplasmin, factor VIII, and fibrinogen followed administration of 1.8, 2.7, 3.7 and 4.6 mg/kg of (Δ K2-5) plasmin, with nadir fibrinogen concentrations of 65%, 40%, 30%, and 0% of initial levels, respectively. Mean primary bleeding time was undisturbed at 1.8 mg/kg (2.2 ± 0.7 minutes), minimally prolonged at 2.7 or 3.7 mg/kg (5 ± 2.9 and 4.4 ± 2.2 minutes), and prolonged at the purposefully toxic 4.6 mg/kg dose (12.8 ± 18.8 minutes). Equimolar amounts of (Δ K2-5) plasmin and full-length plasmin had equal in vitro clot lysis efficacy, but in the bleeding model, (Δ K2-5) plasmin showed better haemostatic competency than full-length plasmin. This safety advantage may be explained by higher residual amounts of plasma fibrinogen in animals given (Δ K2-5) plasmin rather than full-length plasmin. We demonstrate that a unique recombinant plasmin mutant, (Δ K2-5) plasmin, possesses an advantage in hemostatic safety over an equimolar amount of full-length plasmin.
Topics: Animals; Bleeding Time; Disease Models, Animal; Fibrinolysin; Hemorrhage; Humans; Kringles; Protein Interaction Domains and Motifs; Rabbits; Recombinant Proteins; Sequence Deletion; Thrombolytic Therapy; Thrombosis; Tissue Plasminogen Activator
PubMed: 20806125
DOI: 10.1160/TH09-10-0742 -
Clinical and Applied... Jul 2005Reliable data on plasmin activities in blood of patients during fibrinolytic treatment are lacking. This is due to continuing plasminogen activation by plasminogen...
Reliable data on plasmin activities in blood of patients during fibrinolytic treatment are lacking. This is due to continuing plasminogen activation by plasminogen activators after blood withdrawal. The purpose of this study was to establish a new method for stabilization of blood and to detect plasmin activity in stabilized plasma. For optimization of plasma stabilization by arginine, 50 microL pooled normal citrated plasma was incubated with 50 microL of 0 to 1500 mM arginine, pH 8.7, and 25 microL 100 IU/mL u-PA, 1250 IU/mL t-PA, 10000 U/mL reteplase, 400 U/mL plasminogen-streptokinase-activator complex, 10 microg/mL tenecteplase in 6% BSA-PBS or 25 microL 25 microg/mL plasmin in 20% glycerol. Twenty-five microliters 3 mM HD-Val-Leu-Lys-pNA were added immediately (1 step) or after 90 minutes (room temperature [RT]). The same experiment was performed with pooled normal citrated plasma supplemented with 3.2 mg/mL EDTA, preoxidized with 0 mM or 20 mM chloramine-T for 10 minutes (37 degrees C). For optimization of plasmin activity, the oxidation time of the arginine-stabilized plasma sample containing 0.5 U/mL active plasmin and the chloramine-T amount was varied. Citrated plasma is stabilized against the in vitro action of all six plasminogen activators tested if the final arginine concentration is greater than 500 mM. Neither the addition of EDTA nor the addition of chloramine-T changes this plasma-stabilizing power of arginine. The optimized functional plasmin assay consists of incubation of 10 microL arginine-stabilized plasma with 10 microL 1.5 M arginine, pH 8.7, and 10 microL 100 mM CT in PBS. After 30 minutes (37 degrees C), 75 microL 1.2 M KCl, 1.6 M Arg, 0.75 mM Val-Leu-Lys-pNA (Stop-CS Reagent), and 175 microL 6% BSA-PBS are added and the absorbance increase (DeltaA) at 405 nm is determined. With the present arginine stabilization procedure of plasma and the determination of plasmin activity in arginine-stabilized plasma as described, it is feasible to determine the activity of plasmin in blood of patients receiving fibrinolytic treatment without artefactual in vitro changes in the samples.
Topics: Arginine; Blood Specimen Collection; Edetic Acid; Fibrinolysin; Humans; Kinetics; Oxidation-Reduction
PubMed: 16015416
DOI: 10.1177/107602960501100309 -
Seminars in Thrombosis and Hemostasis Jun 2013
Topics: Fibrinolysin; Fibrinolysis; Humans; Plasminogen
PubMed: 23712353
DOI: 10.1055/s-0033-1343616 -
Microbial Pathogenesis Jul 1988Certain Group A beta-hemolytic streptococci express a receptor that is capable of specifically binding the human plasma protease plasmin. Once bound, plasmin remains...
Certain Group A beta-hemolytic streptococci express a receptor that is capable of specifically binding the human plasma protease plasmin. Once bound, plasmin remains enzymatically active and is unregulated by its naturally occurring inhibitor alpha-2-antiplasmin (Lottenberg, R., C. C. Broder and M. D. P. Boyle, 1987. Infect. Immun. 55: 1914-1918). In this study certain characteristics of the interaction between plasmin and the receptor expressed on a group A beta-hemolytic streptococcus, strain 64/14, were examined. Binding occurred optimally at physiologic pH and ionic strength. The KD was 5 x 10(-11) M and there were approximately 800 receptors per bacterium. Mouse passage of strain 64 had no significant effect on the KD of the receptor. Binding of plasmin to the bacteria was inhibited by lysine and epsilon-aminocaproic acid in a concentration dependent manner. Similarly these amino acids would displace pre-bound plasmin from the bacteria. These findings suggest a role for plasmin's high affinity lysine binding site in the interaction of plasmin with the bacteria.
Topics: Aminocaproic Acid; Arginine; Binding, Competitive; Cations, Divalent; Fibrinolysin; Humans; Hydrogen-Ion Concentration; Kinetics; Lysine; Plasminogen; Streptococcus pyogenes
PubMed: 2977421
DOI: 10.1016/0882-4010(88)90077-0