A lipid peroxidation product 9-oxononanoic acid induces phospholipase A<sub>2</sub> activity and thromboxane A<sub>2</sub> production in human blood
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- Ren Rendong
- Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University
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- Hashimoto Takashi
- Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University
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- Mizuno Masashi
- Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University
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- Takigawa Hirosato
- Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University
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- Yoshida Masaru
- Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University
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- Azuma Takeshi
- Department of Internal Medicine, Kobe University Graduate School of Medicine
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- Kanazawa Kazuki
- Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University
Bibliographic Information
- Other Title
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- A lipid peroxidation product 9-oxononanoic acid induces phospholipase A2 activity and thromboxane A2 production in human blood
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Abstract
Lipid peroxidation products are known to cause toxicity by reacting with biologically significant proteins, but the inducing role of peroxidation products has been not noted to produce degenerative disease-related eicosanoids. Here, 9-oxononanoic acid (9-ONA), one of the major products of peroxidized fatty acids, was found to stimulate the activity of phospholipase A2 (PLA2), the key enzyme to initiate arachidonate cascade and eicosanoid production. An exposure of fresh human blood to the atmosphere at 37°C accumulated 9-ONA, increasing peroxide value and thiobarbituric acid reactive substances in the blood. The lipid peroxidation was accompanied by significant increases of PLA2 activity and thromboxane B2 (TxB2) production, which is a stable metabolite of thromboxane A2 (TxA2) and a potent agonist of platelet aggregation. These events were abolished by standing the blood under nitrogen. The addition of organically synthesized 9-ONA resumed the activity of PLA2 and the production of TxB2. Also, 9-ONA induced platelet aggregation dose-dependently. These results indicated that 9-ONA is the primary inducer of PLA2 activity and TxA2 production, and is probably followed by the development of diseases such as thrombus formation. This is the first report to find that a lipid peroxidation product, 9-ONA, stimulates the activity of PLA2.
Journal
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- Journal of Clinical Biochemistry and Nutrition
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Journal of Clinical Biochemistry and Nutrition 52 (3), 228-233, 2013
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