Regulation of leukocyte and platelet lipoxygenases by hydroxyeicosanoids.
Regulation of leukocyte and platelet lipoxygenases by hydroxyeicosanoids.
复制标题
羟基类二十烷酸对白细胞和血小板脂氧合酶的调节。
DOI：
10.1016/0006-2952(82)90627-x
复制
发表时间：
1982
影响因子：
5.8
通讯作者：
Bailey,JM
中科院分区：
文献类型：
--
作者：
Vanderhoek,JY;Bryant,RW;Bailey,JM
在过敏和炎症反应期间，花生四烯酸被脂氧合酶氧化成各种生物活性产物，包括白三烯。调节不同脂氧合酶活性的机制尚未明确。我们在这里报告，[14 C]花生四烯酸代谢的5-和15-脂氧合酶的活动，在兔白细胞和12-脂氧合酶在兔血小板被抑制各种羟基二十碳四烯酸（HETE）。15-HETE是5-和12-脂氧合酶的最有效的抑制剂，而5-HETE和12-HETE作用于15-脂氧合酶观察到类似的抑制效力。这三种酶途径对自身产物HETE的敏感性均最低。为了确定15-HETE的哪些结构特征对于抑制5-脂氧合酶是必不可少的，制备了各种衍生物并通过高压液相色谱法纯化，并且通过气相色谱-质谱法确认了它们的结构。具有不同不饱和度的15-HETE类似物的抑制效力为三个双键>4>2>0。15-羟基过氧-5，8，11，13-二十碳四烯酸（15-HPETE）的效力是15-HETE的4倍。15-乙酰氧基、15-酮基和甲酯衍生物的活性与15-HETE相当，而15-乙酰氧基甲酯衍生物的效力较低。基于所观察到的抑制模式，我们假设，复杂的相互调节的关系存在于各种脂氧合酶之间，含有这些脂氧合酶的细胞可以通过它们的脂氧合酶代谢产物相互作用。
During allergic and inflammatory reactions, arachidonic acid is oxidised by lipoxygenases to a variety of biologically active products, including leukotrienes. The mechanisms for regulation of the different lipoxygenase activities are not well defined. We report here that [14C]arachidonic acid metabolism by the 5- and 15-lipoxygenase activities in rabbit leukocytes and the 12-lipoxygenase in rabbit platelets is inhibited by various hydroxyeicosatetraenoic acids (HETEs). 15-HETE was the most effective inhibitor of the 5- and 12-lipoxygenases, whereas similar inhibitory potencies were observed for 5-HETE and 12-HETE acting on the 15-lipoxygenase. These three enzyme pathways were all least sensitive to their own product HETEs. To determine which structural characteristics of 15-HETE are essential for inhibition of the 5-lipoxygenase, various derivatives were prepared and purified by high pressure liquid chromatography, and their structures were confirmed by gas chromatography-mass spectrometry. The inhibitory potencies of 15-HETE analogs with different degrees of unsaturation were in the order of three double bonds >4>2>0. 15-Hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE) was four times more potent than 15-HETE. The 15-acetoxy, 15-keto and methyl ester derivatives were of comparable activity to 15-HETE, and the 15-acetoxy methyl ester derivative was less potent. Based upon the observed patterns of inhibition, we postulate that complex interregulatory relationships exist between the various lipoxygenases, and that cells containing these lipoxygenases may interact with each other via their lipoxygenase metabolites.