Reversible and Irreversible Alterations of Human Plasminogen Indicated by Changes in Susceptibility to Plasminogen Activators and in Response to ∈-Aminocaproic Acid

Thorsen, Sixtus; Kok, Preben; Astrup, Tage

doi:10.1055/s-0038-1647702

Cited by 26 publications

(19 citation statements)

References 11 publications

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“…This form is converted by plasmin into a modified form with a NH2-terminal lysine releasing peptides from the NH2-terminal portion (CLAEYS et al, 1973;SUMMARIA et a!., 1975;VIOLAND and CASTELLINO, 1976). The modified form has a stronger affinity for fibrin (THORSEN,1975) and is more easily activated by a plasminogen activator than the native form (CLAEYS and VERMYLEN, 1974;THORSEN et al, 1974). These properties of the modified form support the above hypothesis on fibrin clot dissolution.…”

mentioning

confidence: 59%

Production of the modified form of human plasminogen by .ALPHA.2-macroglobulin-plasmin complexes.

et al. 1985

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It has been speculated that the modified form of plasminogen, a precursor of proteolytic enzyme plasmin in plasma, plays an important role in fibrinolysis in the blood. The present study was undertaken to examine the production by a2-macroglobulin-plasmin complexes. a2-macroglobulin-plasmin complexes were purified from urokinase-activated plasma by affinity chromatography on lysine-Sepharose and gel filtration on Ultrogel AcA 22. The plasmin complex converted native plasminogen into the modified form more easily in the presence of s-aminocaproic acid.The modification of native plasminogen by a2-macroglobulin-bound plasmin was completely inhibited by aprotinin, and partly by soybean trypsin inhibitor. a2-macroglobulin-bound plasmin produced modified plasminogen in human plasma where potent plasmin inhibitors exist, though the degree of production was small. The present results support the speculation of the important role of the modified form in vivo.

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mentioning

confidence: 59%

Production of the modified form of human plasminogen by .ALPHA.2-macroglobulin-plasmin complexes.

et al. 1985

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“…This form is converted into a modified form with NH2-terminal lysine by plasmin with the release of peptides from the NH2-terminal portion (CLAEYS et al, 1973;SUMMARIA et al, 1975;VIOLAND and CASTELLINO, 1976). The modified form has a stronger affinity for fibrin (THORSEN,1975) and is more easily activated by a plasminogen activator than the native form (CLAEYS and VERMYLEN, 1974;THORSEN et al, 1974). These properties of the modified form support the hypothesis.…”

mentioning

confidence: 67%

“…This suggests that the modified plasminogen may be partly produced in the preparation process and WIMAN, 1970WIMAN, , 1972RICKLI and CUENDET, 1971;ROBBINS et al, 1972) is converted into a modified form with NH2-terminal lysine by plasmin (CLAEYS et al, 1973;SUMMARIA et al, 1975;VIOLAND and CASTELLINO, 1976). It has been suggested that the modified form might play an important role in dissolution of fibrin in vivo (CLAEYS and VERMYLEN, 1974;THORSEN et al, 1974;THORSEN, 1975). Nevertheless, conversion of the native form into a modified form has been considered difficult to occur in plasma containing an excess amount of a2-plasmin inhibitor (MOROI and AOKI, 1976;MULLERTZ, 1979).…”

Section: Resultsmentioning

confidence: 99%

Production of the modified form of human plasminogen in the plasma activated by urokinase.

et al. 1983

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“…Structural analysis of murine plasminogen revealed the presence of a functional lysine-binding site in kringles 1-3 (LBSI) and in kringle 4 (LBSII), whereas low-molecular-mass plasminogen (kringle 5 and the proteinase part) did not bind to lysine; these properties are very similar to those of human plasminogen [26]. Addition of the lysine analogue EAhx to total murine plasminogen and to plasminogen I or I1 resulted in a drastically enhanced activation rate by u-PA, probably as a result of a conformational change in the plasminogen molecule yielding a more readily activatable Lys-plasminogen-like structure [27].…”

Section: Discussionmentioning

confidence: 99%

Characterization of the murine plasminogen/urokinase‐type plasminogen‐activator system

Lijnen

Hoef

Collen

1996

European Journal of Biochemistry

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The murine plasminogenhrokinase-type plasminogen-activator (u-PA) system was studied using purified proteins, plasina and endothelioma cells. Recombinant murine u-PA was obtained as a single-chain molecule of 45 kDa which was converted to two-chain u-PA with plasmin by cleavage of the Lys159-Ilel60 peptide bond. Murine plasminogen, purified from plasma as a single-chain protein of 95 kDa, was resistant to quantitative activation with murine recombinant two-chain u-PA: only 15 % activation within 1 h at 37°C was obtained in mixtures of 1 pM plasminogen and 5 nM recombinant two-chain u-PA, whereas quantitative activation was observed in the autologous human system. Addition of 6-aminohexanoic acid to native murine plasminogen resulted in quantitative activation within 1 h. In murine plasma in vitro, plasminogen was also resistant to quantitative activation with u-PA (50 % activation within 1 h at 37°C with 50nM recombinant two-chain u-PA, whereas in the human system nearly quantitative activation was obtained). Murine plasma clots submerged in murine plasma were resistant to lysis with u-PA; c 2 % clot lysis in 2 h was obtained with 80 nM recombinant two-chain u-PA in the autologous murine system whereas SO % clot lysis in 2 h required only 15 nM recombinant two-chain u-PA in the autologous human system. Saturable binding of murine recombinant two-chain u-PA was observed to murine endothelioma cells that are genetically deficient in u-PA (u-PA-/+ End cells). Binding was characterized by a K,, of 5.5 nM and 800 000 binding siteskell. However, u-PA-'-End cells did not significantly stimulate the activation rate of murine plasminogen by murine recombinant two-chain u-PA and did not enhance the plasminmediated conversion rate of murine recombinant single-chain u-PA to its two-chain derivative. Murine recombinant two-chain u-PA bound to murine endothelioma cells was quantitatively inhibited by murine plasminogen-activator inhibitor-I (PAI-1). Thus, the interactions between murine plasrninogen, u-PA and PAI-1 are qualitatively similar to those between their human counterparts. However, quantitative differences were observed both in the presence of cells and in plasma which may contribute to a reduced u-PA-mediated fibrinolytic activity in the murine systems.Keywords: urokinase-type plasminogen activator; murine fibrinolysiq; plasminogen ; endothelioma cell.The fibrinolytic system in mammalian blood comprises an inactive proenzyme, plasminogen, that is converted to the active enzyme, plasmin, by two immunologically distinct physiological plasminogen activators : the tissue-type plasminogen activator (t-PA) and the urokinase-type plasminogen activator (u-PA). Inhibition of plasmin occurs mainly by a,-antiplasmin and inhibition of t-PA and u-PA mainly by plasminogen-activator inhibitor-1 (PAI-1). t-PA-mediated plasminogen activation is mainly responsible for the dissolution of fibrin in the circulation [I]. u-PA binds to a specific cellular receptor (u-PAR) and activates cell-bound plasminogen into cell-associated plasmin ...

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Reversible and Irreversible Alterations of Human Plasminogen Indicated by Changes in Susceptibility to Plasminogen Activators and in Response to ∈-Aminocaproic Acid

Cited by 26 publications

References 11 publications

Production of the modified form of human plasminogen by .ALPHA.2-macroglobulin-plasmin complexes.

Production of the modified form of human plasminogen by .ALPHA.2-macroglobulin-plasmin complexes.

Production of the modified form of human plasminogen in the plasma activated by urokinase.

Characterization of the murine plasminogen/urokinase‐type plasminogen‐activator system

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