title: Characterization and biological effects of di-hydroxylated compounds deriving from the lipoxygenation of ALA.
abstract: 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.
authors.affiliation: Université de Lyon, UMR 1060 Inserm (CarMeN), IMBL/INSA-Lyon, 69621 Villeurbanne, France.
authors.forename: Miao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Tea Science Department, College of Agriculture and Biotechnology, Zhejiang University, 310029 Hangzhou, China; and.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Université de Lyon, UMR 1060 Inserm (CarMeN), IMBL/INSA-Lyon, 69621 Villeurbanne, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Véricel
authors.affiliation: Centre de RMN à Très Hauts Champs, Université de Lyon (CNRS/ENS Lyon/UCB Lyon 1), 69100 Villeurbanne, France.
authors.forename: Moreno
authors.initials: M
authors.lastname: Lelli
authors.affiliation: Centre de RMN à Très Hauts Champs, Université de Lyon (CNRS/ENS Lyon/UCB Lyon 1), 69100 Villeurbanne, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Béguin
authors.affiliation: Université de Lyon, UMR 1060 Inserm (CarMeN), IMBL/INSA-Lyon, 69621 Villeurbanne, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Lagarde
authors.affiliation: Université de Lyon, UMR 1060 Inserm (CarMeN), IMBL/INSA-Lyon, 69621 Villeurbanne, France. Electronic address: michel.guichardant@insa-lyon.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Guichardant
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects; D006801:Humans; D006900:Hydroxylation; D015394:Molecular Structure; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D017962:alpha-Linolenic Acid / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011994:Recombinant Proteins; D017962:alpha-Linolenic Acid; C458528:ALOX15B protein, human; D001093:Arachidonate 15-Lipoxygenase
keywords: 15-lipoxygenase; anti-inflammatory activity; octadecatrienoic acid; platelet aggregation; α-linolenic acid