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Related Experiment Video

Updated: Dec 29, 2025

A Liposome Membrane Permeability Assay for Investigating the Effects of Phosphatidylinositol Phosphate Groups on Membranotropic Action of Venom PLA2

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uPA-mediated plasminogen activation is enhanced by polyphosphate.

Claire S Whyte¹, Nicola J Mutch¹

¹University of Aberdeen.

|February 8, 2020

Summary

Polyphosphate (polyP) differentially affects fibrinolysis. While polyP inhibits tissue plasminogen activator (tPA)-mediated clot breakdown, it significantly enhances urokinase (uPA)-mediated fibrinolysis by promoting plasmin generation.

Area of Science:

Biochemistry
Hematology
Molecular Biology

Background:

Tissue plasminogen activator (tPA) and urokinase (uPA) are serine proteases that activate plasminogen to plasmin, initiating fibrinolysis.
tPA activity is fibrin-dependent, requiring binding to fibrin for efficient plasminogen activation.
uPA is fibrin-independent, activating plasminogen in solution or via its receptor, uPAR.
Polyphosphate (polyP) has been shown to alter fibrin structure and inhibit tPA-mediated fibrinolysis.

Purpose of the Study:

To investigate the impact of polyphosphate (polyP) on urokinase (uPA)-mediated fibrinolysis.
To compare the effects of polyP on tPA- and uPA-mediated plasminogen activation and fibrinolysis.

Main Methods:

Assessed fibrinolysis rates in polyP-containing clots using tPA and uPA.

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Measured plasmin generation rates in real-time using confocal microscopy.

Investigated the influence of varying plasminogen concentrations on tPA- and uPA-mediated fibrinolysis.

Main Results:

Polyphosphate (polyP65) significantly delayed and reduced tPA-mediated plasmin generation and fibrinolysis.
In contrast, polyP65 markedly augmented uPA-mediated plasmin generation (4.7-fold) and accelerated fibrinolysis.
The accelerating effect of polyP65 on uPA activity was dose-dependent on plasminogen concentration and could be overcome by excess plasminogen.

Conclusions:

Polyphosphate exerts opposing effects on tPA- and uPA-mediated fibrinolysis.
PolyP attenuates the fibrin cofactor function essential for tPA activity.
PolyP may facilitate fibrin-independent interactions between uPA and plasminogen, thereby enhancing fibrinolysis.