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Increased thromboxane B2 biosynthesis in platelets.

H Kawaguchi, T Ishibashi, Y Imai

    Lipids
    |September 1, 1982
    PubMed
    Summary
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    Platelets from hypercholesterolemic rabbits show increased thromboxane B2 synthesis, linked to decreased glutathione and glutathione peroxidase. These factors likely drive elevated thromboxane B2 production in this condition.

    Area of Science:

    • Biochemistry
    • Cardiovascular Research
    • Platelet Biology

    Background:

    • Hypercholesterolemia elevates thromboxane B2 synthesis in rabbit platelets.
    • The underlying mechanism for this increase requires clarification.

    Purpose of the Study:

    • To elucidate the mechanism behind increased thromboxane B2 synthesis in hypercholesterolemic rabbit platelets.
    • To investigate the role of reactive oxygen species, singlet oxygen, and glutathione metabolism in this process.

    Main Methods:

    • Enzyme assays using partially purified enzymes and platelet microsomes.
    • Investigating the effects of various compounds (superoxide dismutase, deuterium oxide, ADP-Fe3+, glutathione) on prostaglandin H2 and thromboxane B2 biosynthesis.
    • Measuring glutathione concentration and glutathione peroxidase activity in platelets from normal and hypercholesterolemic rabbits.

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    Main Results:

    • Superoxide dismutase and related compounds did not affect prostaglandin H2 and thromboxane B2 biosynthesis, suggesting reactive oxygen species are not involved.
    • Deuterium oxide promoted prostaglandin H2 biosynthesis, reversed by 2,5-diphenylfuran, indicating potential involvement of singlet oxygen.
    • Glutathione and glutathione peroxidase inhibited cyclooxygenase but not thromboxane synthetase. Both were decreased in hypercholesterolemic rabbits.
    • Hydrogen peroxide inactivated cyclooxygenase but did not inhibit thromboxane B2 formation from prostaglandin H2.

    Conclusions:

    • Decreased glutathione levels and glutathione peroxidase activity in hypercholesterolemic rabbit platelets likely contribute to increased thromboxane B2 synthesis.
    • Singlet oxygen may play a role in prostaglandin H2 biosynthesis.
    • While altered glutathione metabolism is a significant factor, other unidentified mechanisms might also contribute to elevated thromboxane B2 synthesis.