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Related Experiment Videos

Actin accelerates plasmin generation by tissue plasminogen activator.

S E Lind1, C J Smith

  • 1Hematology Unit, Massachusetts General Hospital, Boston.

The Journal of Biological Chemistry
|September 15, 1991
PubMed
Summary
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Actin enhances plasmin generation from plasminogen by tissue plasminogen activator (t-PA). This interaction, involving lysine residues, suggests a role for actin in blood changes following injury or sepsis.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Hemostasis

Background:

  • Actin is known to bind plasmin's kringle regions, inhibiting its activity.
  • The interaction between actin and the fibrinolytic system, specifically plasminogen activation, requires further investigation.

Purpose of the Study:

  • To investigate the effect of actin on the activation of plasminogen to plasmin by tissue plasminogen activator (t-PA).
  • To elucidate the mechanisms underlying actin's influence on plasmin generation.

Main Methods:

  • Assessed plasmin generation from Glu- and Lys-plasminogen in the presence of actin and t-PA.
  • Investigated the role of lysine residues using epsilon-amino caproic acid and acetic anhydride.
  • Determined the binding affinity of actin to t-PA using surface plasmon resonance.

Related Experiment Videos

  • Examined the effect of aprotinin and plasmin-treated actin on plasmin generation.
  • Evaluated the impact of actin and t-PA on plasma thrombin time.

    • Main Results:

    • Actin significantly stimulated plasmin generation from both Glu- and Lys-plasminogen, reducing the Km for Glu-plasminogen activation.
    • Actin binds to t-PA (Kd = 0.55 microM) via lysine-binding sites, and this interaction is crucial for accelerated plasmin generation.
    • A plasmin-dependent positive feedback mechanism was identified, where plasmin-treated actin enhances plasminogen activation.
    • Actin and t-PA, in combination, prolong thrombin time by generating plasmin and fibrinogen degradation products.

    Conclusions:

    • Actin acts as a potent stimulator of plasminogen activation by t-PA, primarily through interactions involving lysine residues and a positive feedback loop.
    • The findings suggest that actin-mediated plasmin generation may contribute to physiological changes observed in peripheral blood after tissue injury and sepsis.