Characterization and biological effects of di-hydroxylated compounds deriving from the lipoxygenation of ALA
Characterization and biological effects of di-hydroxylated compounds deriving from the lipoxygenation of ALA
复制标题
ALA 脂氧合衍生的二羟基化合物的表征和生物效应
DOI：
10.1194/jlr.m035139
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发表时间：
2013-08-01
影响因子：
6.5
通讯作者：
Guichardant, Michel
中科院分区：
文献类型：
--
作者：
Liu, Miao;Chen, Ping;Guichardant, Michel
我们最近描述了一种名为保护素DX(PDX)的双羟基化化合物，它是由二十二碳六烯酸(DHA)通过双重脂肪氧合而成的。PDX具有抗聚集性和抗炎性，类似的分子也表现出这些特性，称为POXYTRINS，它具有相同的E，Z，E共轭三烯构型，由其他含有22或20个碳的多不饱和脂肪酸合成。本文报道了大豆15-脂氧合酶(SLOX)处理α-亚麻酸(18：3n-3)产生的二羟基代谢物的新生物活性。结果表明，过氧化氢还原后，18：3N-3被SLOX转化为主要的13(S)-OH-18：3。但令人惊讶的是，与只代谢成一种二羟基化合物的DHA不同，18：3n-3会导致四种二羟基脂肪酸异构体。我们在这里报道了这些化合物的高场核磁共振和GC-MS技术的完整表征，以及它们的一些生物活性。这些化合物是：9(R)，16(S)-dihydroxy-10E，12E，14E-octadecatrienoic酸、9(S)，16(S)-dihydroxy-10E，12E，14E-octadecatrienoic酸、9(S)，16(S)-dihydroxy-10E，12Z，14E-octadecatrienoic酸和9(R)，16(S)-dihydroxy-10E，12Z，14E-octadecatrienoic酸。它们也可以由人重组的15-脂氧合酶(2型)合成。将它们对血小板的抑制作用和抗炎特性与已报道的PDX进行了比较。
We have recently described a di-hydroxylated compound called protectin DX (PDX) which derives from docosahexaenoic acid (DHA) by double lipoxygenation. PDX exhibits anti-aggregatory and anti-inflammatory properties, that are also exhibited by similar molecules, called poxytrins, which possess the same E,Z,E conjugated triene geometry, and are synthesized from other polyunsaturated fatty acids with 22 or 20 carbons. Here we present new biological activities of di-hydroxylated metabolites deriving from α-linolenic acid (18:3n-3) treated by soybean 15-lipoxygenase (sLOX). We show that 18:3n-3 is converted by sLOX into mainly 13(S)-OH-18:3 after reduction of the hydroperoxide product. But surprisingly, and in contrast to DHA which is metabolized into only one di-hydroxylated compound, 18:3n-3 leads to four di-hydroxylated fatty acid isomers. We report here the complete characterization of these compounds using high field NMR and GC-MS techniques, and some of their biological activities. These compounds are: 9(R),16(S)-dihydroxy-10E,12E,14E-octadecatrienoic acid, 9(S),16(S)-dihydroxy-10E,12E,14E-octadecatrienoic acid, 9(S),16(S)-dihydroxy-10E,12Z,14E-octadecatrienoic acid, and 9(R),16(S)-dihydroxy-10E,12Z,14E-octadecatrienoic acid. They can also be synthesized by the human recombinant 15-lipoxygenase (type 2). Their inhibitory effect on blood platelet and anti-inflammatory properties were compared with those already reported for PDX.