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Related Experiment Videos

The inhibition of platelet-activating factor-induced platelet activation by oleic acid is associated with a decrease

D Nunez1, J Randon, C Gandhi

  • 1Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760.

The Journal of Biological Chemistry
|October 25, 1990
PubMed
Summary

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Oleic acid, a free fatty acid, inhibits platelet-activating factor (PAF) induced platelet aggregation by decreasing phosphatidylinositol 4,5-bisphosphate (PIP2) levels. This suggests oleic acid interferes with PAF signal transduction pathways.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Platelet-activating factor (PAF) is a potent mediator of platelet aggregation.
  • Unsaturated free fatty acids (FFA), including oleic acid, were identified as inhibitors of PAF.
  • Oleic acid (10-100 microM) inhibits PAF-induced platelet aggregation and serotonin secretion.

Purpose of the Study:

  • To elucidate the molecular mechanism by which oleic acid inhibits PAF-induced platelet aggregation.
  • To investigate the effects of oleic acid on biochemical events in platelets stimulated by PAF.

Main Methods:

  • Platelets were labeled with [32P]phosphate or [3H]inositol.
  • The levels of [32P]phosphatidylinositol 4-phosphate (PIP) and [32P]phosphatidylinositol 4,5-bisphosphate (PIP2) were measured.

Related Experiment Videos

  • The effect of oleic acid and PAF on [3H]inositol phosphate formation was assessed.
  • Binding of [3H]PAF to platelets and PAF-induced protein phosphorylation were examined.

    • Main Results:

    • Oleic acid caused a dose-dependent decrease in [32P]PIP and [32P]PIP2 levels.
    • PAF increased [32P]PIP levels and induced platelet aggregation and secretion.
    • Oleic acid's effect on PIP and PIP2 was partially reversed by excess PAF.
    • Oleic acid inhibited PAF-induced phosphorylation of 20 kDa and 40 kDa platelet proteins.
    • Oleic acid did not inhibit [3H]PAF binding to platelets.

    Conclusions:

    • Oleic acid inhibits PAF-induced platelet aggregation and secretion.
    • The mechanism involves a decrease in PIP and PIP2 levels, suggesting interference with signal transduction.
    • Oleic acid likely acts downstream of PAF binding but upstream of protein phosphorylation.