脂质过氧化产物9-氧代壬酸诱导人血中的磷脂酶A2活性和血栓烷A2产生,Journal of Clinical Biochemistry and Nutrition

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脂质过氧化产物9-氧代壬酸诱导人血中的磷脂酶A2活性和血栓烷A2产生
Journal of Clinical Biochemistry and Nutrition Pub Date : 2013-01-01 , DOI: 10.3164/jcbn.12-110
Rendong Ren , Takashi Hashimoto , Masashi Mizuno , Hirosato Takigawa , Masaru Yoshida , Takeshi Azuma , Kazuki Kanazawa

已知脂质过氧化产物会通过与生物学上重要的蛋白质反应而引起毒性，但尚未发现过氧化产物的诱导作用会产生与疾病有关的变性类花生酸。在这里，发现过氧化脂肪酸的主要产物之一9-氧代壬酸（9-ONA）可以刺激磷脂酶A2（PLA2）的活性，磷脂酶A2是引发花生四烯酸级联和类花生酸生产的关键酶。新鲜人类血液在37°C的大气中累积会累积9-ONA，从而增加血液中的过氧化物值和硫代巴比妥酸反应性物质。脂质过氧化伴随着PLA2活性和血栓烷B2（TxB2）产量的显着增加，血栓烷B2（TxA2）是血栓烷A2（TxA2）的稳定代谢产物，是血小板凝集的有效激动剂。将血液置于氮气下可废除这些事件。有机合成的9-ONA的添加恢复了PLA2的活性和TxB2的产生。同样，9-ONA剂量依赖性地诱导血小板凝集。这些结果表明9-ONA是PLA2活性和TxA2产生的主要诱因，并且可能继之以疾病的发展，例如血栓形成。这是第一个发现脂质过氧化产物9-ONA刺激PLA2活性的报告。并可能随后发展为诸如血栓形成的疾病。这是第一个发现脂质过氧化产物9-ONA刺激PLA2活性的报告。并可能随后发展为诸如血栓形成的疾病。这是第一个发现脂质过氧化产物9-ONA刺激PLA2活性的报告。

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A lipid peroxidation product 9-oxononanoic acid induces phospholipase A2 activity and thromboxane A2 production in human blood

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.

更新日期：2013-01-01

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