阿司匹林可增强人类血小板12-脂氧合酶对内源性调节剂15-羟基二十碳四烯酸（15-HETE）抑制作用的敏感性。

Aspirin enhances the sensitivity of human platelet 12-lipoxygenase to inhibition by 15-HETE, an endogenous regulator.

作者信息

Fletcher-Cieutat M, Vanderhoek J Y, Bryant R W, Bailey J M

出版信息

Prostaglandins Leukot Med. 1985 May;18(2):255-9. doi: 10.1016/0262-1746(85)90025-3.

DOI:10.1016/0262-1746(85)90025-3

Abstract

Human platelets metabolize arachidonic acid via cyclooxygenase (E.C. 1.14.99.1) to thromboxane A2 and the 12-lipoxygenase to 12-hydroxyeicosatetraenoic acid (12-HETE). Aspirin inhibits cyclooxygenase while the neutrophil product 15-Hydroxyeicosatetraenoic acid (15-HETE) is a selective inhibitor of platelet 12-lipoxygenase. The unexpected observation was made that the platelet 12-lipoxygenase of individuals who had ingested aspirin showed up to a twenty-fold increase in sensitivity to inhibition by 15-HETE. This observation was confirmed in platelets treated with aspirin in vitro. Aspirin pretreatment consistently resulted in a decrease in the I50 for 15-HETE from an average of 21.5 microM to only 5.2 +/- 1.5 microM, indicating a probable interaction between the cyclooxygenase and lipoxygenase pathways.

摘要

人类血小板通过环氧合酶（E.C. 1.14.99.1）将花生四烯酸代谢为血栓素A2，并通过12-脂氧合酶将其代谢为12-羟基二十碳四烯酸（12-HETE）。阿司匹林抑制环氧合酶，而中性粒细胞产物15-羟基二十碳四烯酸（15-HETE）是血小板12-脂氧合酶的选择性抑制剂。有一个意外的发现，即摄入阿司匹林的个体的血小板12-脂氧合酶对15-HETE抑制的敏感性提高了多达20倍。这一发现在用阿司匹林体外处理的血小板中得到了证实。阿司匹林预处理始终导致15-HETE的半数抑制浓度（I50）从平均21.5微摩尔降至仅5.2±1.5微摩尔，表明环氧合酶和脂氧合酶途径之间可能存在相互作用。

相似文献

1

Aspirin enhances the sensitivity of human platelet 12-lipoxygenase to inhibition by 15-HETE, an endogenous regulator.阿司匹林可增强人类血小板12-脂氧合酶对内源性调节剂15-羟基二十碳四烯酸（15-HETE）抑制作用的敏感性。

Prostaglandins Leukot Med. 1985 May;18(2):255-9. doi: 10.1016/0262-1746(85)90025-3.

2

Stimulation of 12-HETE production in human platelets by an immunomodulator, LF 1695. Evidence for activation of arachidonate liberation coupled to cyclo-oxygenase inhibition.免疫调节剂LF 1695对人血小板中12-羟基二十碳四烯酸（12-HETE）生成的刺激作用。花生四烯酸释放激活与环氧化酶抑制相关的证据。

Biochem Pharmacol. 1989 Sep 1;38(17):2763-72. doi: 10.1016/0006-2952(89)90429-2.

3

Effect of adenine nucleotides on cyclooxygenase and lipoxygenase enzyme products of arachidonic acid in human platelets.腺嘌呤核苷酸对人血小板中花生四烯酸的环氧化酶和脂氧化酶产物的影响。

Biochem Pharmacol. 1990 Jan 1;39(1):27-32. doi: 10.1016/0006-2952(90)90644-z.

4

Inhibition of human malignant neuroblastoma cell DNA synthesis by lipoxygenase metabolites of arachidonic acid.花生四烯酸的脂氧合酶代谢产物对人恶性神经母细胞瘤细胞DNA合成的抑制作用。

Cancer Res. 1985 Feb;45(2):561-3.

5

Production of arachidonic acid lipoxygenase products during platelet-neutrophil interactions.血小板与中性粒细胞相互作用过程中花生四烯酸脂氧合酶产物的生成。

Clin Physiol Biochem. 1984;2(2-3):78-83.

6

Role of lipoxygenase metabolism in platelet function: effect of aspirin and salicylate.脂氧合酶代谢在血小板功能中的作用：阿司匹林和水杨酸盐的影响。

Prostaglandins Leukot Med. 1986 Feb;21(2):157-68. doi: 10.1016/0262-1746(86)90149-6.

7

Aspirin inhibits platelet 12-hydroxy-eicosatetraenoic acid formation.阿司匹林抑制血小板12-羟基-二十碳四烯酸的形成。

J Lab Clin Med. 1986 Jan;107(1):73-8.

8

Activation of a 15-lipoxygenase/leukotriene pathway in human polymorphonuclear leukocytes by the anti-inflammatory agent ibuprofen.抗炎药布洛芬对人多形核白细胞中15-脂氧合酶/白三烯途径的激活作用。

J Biol Chem. 1984 Jun 10;259(11):6752-6.

9

Stimulation of the 15-lipoxygenase in activated polymorphonuclear neutrophils. Influence of lipoxygenase inhibitors and hydroxyeicosatetraenoic acid derivatives.激活的多形核中性粒细胞中15-脂氧合酶的刺激作用。脂氧合酶抑制剂和羟基二十碳四烯酸衍生物的影响。

Eicosanoids. 1990;3(3):181-5.

10

Endogenous hydroxyeicosatetraenoic acids stimulate the human polymorphonuclear leukocyte 15-lipoxygenase pathway.内源性羟基二十碳四烯酸刺激人类多形核白细胞15-脂氧合酶途径。

J Biol Chem. 1985 Dec 15;260(29):15482-7.

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