The kinetics of inhibition of tissue-type plasminogen activator (t-PA) by the fast-acting plasminogen activator inhibitor-1 (PAI-1) was investigated in homogeneous (plasma) and heterogeneous (solid-phase fibrin) systems by using radioisotopic and spectrophotometric analysis. It is demonstrated that fibrin-bound t-PA is protected from inhibition by PAI-1, whereas t-PA in soluble phase is rapidly inhibited (K1 = 10(7) M-1.s-1) even in the presence of 2 microM-plasminogen. The inhibitor interferes with the binding of t-PA to fibrin in a competitive manner. As a consequence the Kd of t-PA for fibrin (1.2 +/- 0.4 nM) increases and the maximal velocity of plasminogen activation by fibrin-bound t-PA is not modified. From the plot of the apparent Kd versus the concentration of PAI-1 a Ki value of 1.3 +/- 0.3 nM was calculated. The quasi-similar values for the dissociation constants between fibrin and t-PA (Kd) and between PAI-1 and t-PA (Ki), as well as the competitive type of inhibition observed, indicate that the fibrinolytic activity of human plasma may be the result of an equilibrium distribution of t-PA between both the amount of fibrin generated and the concentration of circulating inhibitor.
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Research Article|
November 15 1988
Kinetic analysis of the interaction between plasminogen activator inhibitor-1 and tissue-type plasminogen activator
C Masson;
C Masson
1I.N.S.E.R.M. U. 143, Institut de Pathologie Cellulaire, Hôpital de Bicêtre, 94275 Bicêtre Cedex, France.
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E Angles-Cano
E Angles-Cano
1I.N.S.E.R.M. U. 143, Institut de Pathologie Cellulaire, Hôpital de Bicêtre, 94275 Bicêtre Cedex, France.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1988 London: The Biochemical Society
1988
Biochem J (1988) 256 (1): 237–244.
Citation
C Masson, E Angles-Cano; Kinetic analysis of the interaction between plasminogen activator inhibitor-1 and tissue-type plasminogen activator. Biochem J 15 November 1988; 256 (1): 237–244. doi: https://doi.org/10.1042/bj2560237
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