1. Characterization and biological effects of di-hydroxylated compounds deriving from the lipoxygenation of ALA
- Author
-
Evelyne Véricel, Michel Lagarde, Ping Chen, Michel Guichardant, Moreno Lelli, Laetitia Beguin, and Miao Liu
- Subjects
Blood Platelets ,Stereochemistry ,α-linolenic acid ,QD415-436 ,Conjugated system ,Hydroxylation ,Biochemistry ,law.invention ,octadecatrienoic acid ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,15-lipoxygenase ,law ,Arachidonate 15-Lipoxygenase ,Humans ,Molecule ,Anti-inflammatory activity ,Octadecatrienoic acid ,Platelet aggregation ,Cell Biology ,anti-inflammatory activity ,Inhibitory effect ,Research Articles ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Molecular Structure ,Chemistry ,Anti-Inflammatory Agents, Non-Steroidal ,alpha-Linolenic Acid ,Fatty acid ,Recombinant Proteins ,platelet aggregation ,Docosahexaenoic acid ,030220 oncology & carcinogenesis ,Recombinant DNA ,Polyunsaturated fatty acid - 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.
- Published
- 2013