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Related Experiment Videos

Prothrombinase acceleration by oxidatively damaged phospholipids.

E A Weinstein1, H Li, J A Lawson

  • 1Department of Pharmacology and Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

The Journal of Biological Chemistry
|May 10, 2000
PubMed
Summary
This summary is machine-generated.

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Oxidative damage to membrane lipids surprisingly enhances prothrombinase activity, increasing thrombin production. Antioxidants like alpha-tocopherol and ascorbate can reverse this effect, suggesting specific oxidation products are responsible.

Area of Science:

  • Biochemistry
  • Membrane Biophysics
  • Hemostasis

Background:

  • Prothrombinase complex activity is crucial for efficient thrombin generation.
  • Phosphatidylserine-rich membranes are essential for optimal prothrombinase complex assembly and function.
  • Oxidative damage to membrane lipids is generally expected to disrupt membrane structure and impair protein function.

Purpose of the Study:

  • To investigate the effect of oxidized phospholipids on prothrombinase complex activity.
  • To determine if oxidative membrane damage inhibits or enhances thrombin production.
  • To identify potential protective agents against observed effects.

Main Methods:

  • Preparation of phosphatidylserine-containing lipid vesicles with oxidized arachidonoyl lipids.

Related Experiment Videos

  • Assay of thrombin production by the prothrombinase complex using these vesicles.
  • Evaluation of the impact of antioxidants (alpha-tocopherol, gamma-tocopherol, ascorbate) on prothrombinase activity.
  • Kinetic analysis of prothrombinase activity over a 300-minute oxidation period.

    • Main Results:

    • Oxidized arachidonoyl lipids dose-dependently increased prothrombinase activity up to 6-fold compared to controls.
    • The enhancing effect of oxidized lipids on prothrombinase activity was fully reversed by alpha-tocopherol, gamma-tocopherol, or ascorbate.
    • Prothrombinase activity enhancement peaked at 60 minutes of oxidation and subsequently declined.

    Conclusions:

    • Contrary to expectations, products of nonenzymatic lipid oxidation enhance, rather than impede, prothrombinase activity.
    • Specific oxidized lipid species appear to modulate the prothrombinase complex, leading to increased thrombin generation.
    • Antioxidants can mitigate the procoagulant effects of oxidized membrane lipids.