RESUMEN
Influence of the end fibrinogen-derived DH, DL and E fragments on fibrinolysis and fibrinogenolysis has been studied. Electrophoresis of the plasmin-digested unstabilized fibrin and fibrinogen showed that fragment E was the only inhibitor of plasmin hydrolysis of fibrinogen, the antifibrinolytic activity of the fragments being increased in a DL < E < DH series. The fragments were revealed by means of elastic light scattering and analytical ultracentrifugation to be arranged in a E > DL > DH series by their ability to form a complex with plasminogen. It was concluded that the complex formation did not greatly contribute to the mechanism of fibrinolysis inhibition. Antifibrinolytic effect of fragment DH is due to its antipolymerization activity. The paper discusses the competitive protein-protein interactions occurring on a polymeric matrix of fibrin.
Asunto(s)
Productos de Degradación de Fibrina-Fibrinógeno/farmacología , Fibrina/metabolismo , Fibrinógeno/metabolismo , Fibrinólisis/efectos de los fármacos , Depresión Química , Fibrinolisina/farmacología , Humanos , Hidrólisis , Plasminógeno/farmacología , Trombina/farmacologíaRESUMEN
The mechanism of effect of plasmin hydrolysis degradation products, fragments DL and DH, on fibrinolysis and fibrinogenolysis processes was investigated on the basis of their various structural and functional characteristics. Using electrophoresis of unreduced samples and degradation products concentrations changing kinetics, DH was shown to be the only fragment which possessed an antifibrinolytic effect. Rauleigh's light scattering analysis indicated the ability of fragments DL and DH to co-form with plasminogen reversible equimolar complexes.
Asunto(s)
Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Fibrina/metabolismo , Fibrinógeno/metabolismo , Fibrinolisina/metabolismo , Electroforesis de las Proteínas Sanguíneas , Electroforesis en Gel de Poliacrilamida , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/aislamiento & purificación , Fibrinólisis , Humanos , Hidrólisis , Técnicas In Vitro , Luz , Peso Molecular , Dispersión de Radiación , Relación Estructura-ActividadAsunto(s)
Productos de Degradación de Fibrina-Fibrinógeno/farmacología , Fibrinolisina/antagonistas & inhibidores , Fenómenos Químicos , Química Física , Cromatografía de Afinidad , Electroforesis en Gel de Poliacrilamida , Productos de Degradación de Fibrina-Fibrinógeno/química , Productos de Degradación de Fibrina-Fibrinógeno/aislamiento & purificación , Fibrinólisis/efectos de los fármacos , Fibrinólisis/fisiología , HumanosRESUMEN
The effect of D-dimer on the process of plasmin hydrolysis of unstabilized and crosslinked fibrin has been studied. Less degraded early, intermediate, and late products of fibrin cleavage have been revealed by electrophoresis of reduced and nonreduced samples. The molecular mechanism of antifibrinolytic effect of the D-dimer is supposed to be determined by shielding of peptide regions of monomer fibrin, localized both in N-terminal area of beta chain and in alpha, beta, and gamma chains between D and E domains. A notion has been proposed of autoinhibition of fibrinolytic reaction as a phenomenon related to the physical-chemical regulation of fibrinogen transformation into fibrin.
Asunto(s)
Antifibrinolíticos/farmacología , Productos de Degradación de Fibrina-Fibrinógeno/farmacología , Antifibrinolíticos/aislamiento & purificación , Electroforesis de las Proteínas Sanguíneas , Fibrina/efectos de los fármacos , Fibrina/metabolismo , Productos de Degradación de Fibrina-Fibrinógeno/aislamiento & purificación , Fibrinógeno/efectos de los fármacos , Fibrinógeno/metabolismo , Fibrinólisis/efectos de los fármacos , Humanos , Relación Estructura-ActividadRESUMEN
The effect of heparin on non-stabilized fibrin hydrolysis by plasmin was investigated. Using analytical centrifugation in the presence of heparin, the existence of a high molecular weight fraction (sedimentation coefficient 17S) was demonstrated. Electrophoretic analysis revealed the presence of less degradable early, intermediate and late fibrin hydrolysis products. It is concluded that the molecular mechanisms of these effects are due to the direct action of heparin on the fibrin-monomer molecule which provides for the inhibition of peptide side chains localized between residues 15 Gly-53 Lys in the NH2-terminal part of the B beta-chain. The universal mechanisms underlying the anti-fibrinolytic activity of high molecular weight inhibitors of fibrin polymerization and aggregation are discussed.