13- Hydroxyoctadecadienoic acid

I3-hydroperoxy-9-cis, I I-tmrw-octadecadienoic acid 9-hydroperoxy-I0-tmrw,I2 cis octadecadienoic acid 9-hydroxy-I0-fmn, I2,I3 cw-epoxyoctadecadienoic acid 9,10 -cis-epoxy-ll-trans-13 hydroxyoctadecadienoic acid... 

Fig. 5. Generation of 155-hydroxyeicosatetraenoic acid (HETE) and 13-hydroxyoctadecadienoic acid (HODE) by 15-lipoxyge-nase (LOX)-1 and -2. HPETE, hydroperoxyeicosatetraenoic acid HPODE, hydroperoxyoctadecadienoic acid.

Fig. 1. Oxidative metabolism of linoleic acid by the human epidermis. Abbreviations 13-HPODE, 13-hydroperoxide octadecadienoic acid 13-HODE, 13-hydroxyoctadecadienoic acid.

Fig. 4. A speculative scenario showing how dietary linoleic acid could suppress skin hyperproliferation via cutaneous generation of putative 13S-hydroxyoctadecadienoic acid (13S-HODE)-substituted diacylglycerol (13S-HODE-DAG). Abbreviations PKC- 3, protein kinase C- 3 protein-P, phosphorylated protein PLC, phospholipid C PIP, phosphatidylinositol phosphate ER, endoplasmic reticulum.

Cho, Y, and Ziboh, VA. (1994) Expression of Protein Kinase C Isozymes in Guinea Pig Epidermis Selective Inhibition of PKC-P Activity by 13-Hydroxyoctadecadienoic Acid-Containing Diacylglycerol, J. Upid Res. 55,913-921. 

Cho, Y. and V. A. Ziboh 1994. 13-Hydroxyoctadecadienoic acid reverses epidermal hyperproliferation via selective inhibition of protein kinase C-beta activity. 

Xi, S., H. Pham et al. 2000. Suppression of proto-oncogene (AP-1) in a model of skin epidermal hypeiproliferation is reversed by topical application of 13-hydroxyoctadecadienoic acid and 15-hydroxyeicosatrienoic acid. 

Beckman et al (1994) used normal-phase HPLC of constituent hydroxy fatty acids followed by GC/MS analysis to reveal that the oxidized GPL in the skin of CDi mice, following application of the tumour-promoter phorbol esters, were oxidized derivatives of linoleic acid, including 9- and 13-hydroxyoctadecadienoic acids (9- and 13-HODE). Sodium borohydride reduction increased product yield by approximately 50%, suggesting the additional presence of GPL hydroperoxides in the oxidized lipids. 

Figure C4.2.3 TLC showing separation of triphenylphosphine-reduced hydroperoxides of linoleic acid using 50 50 1 (v/v/v) hexane/diethyl ether/acetic acid. Short-wave UV visualization reveals unreacted triphenylphosphine (top), hydroxyoctadecadienoic acid (HODE) isomers (middle), and triphenylphosphineoxide (bottom). On the left, mainly 13-HODE (E,Z)-diene isomer is present on the right, a mixture of 9- and 13-HODE, mainly (E,Z)-diene isomers, is present.

Abbreviations. AhR, aromatic hydrocarbon receptor TCDD, tetrachlorodibenzodioxin PXR, pregnenolone-16a-nitrile-X-receptor PCN, pregnenolone-16a-nitrile CAR, constitutive androstane receptor MC, methylcholanthrene PPARa, peroxisome proliferated-activated receptor-a FXR, famesoid-X-receptor LXR, liver-X-receptor RXR, retinod-X-receptor 5-HETE, 5-OH-eicosatetraenoic acid LTB4, leukotriene B4 13-HODE, hydroxyoctadecadienoic acid DMXAA, dimethylxan-thenone-4-acetic acid. 

Also extracted from native HZ were polar hydroxylated fatty acids derived presumably from cellular arachidonic and linoleic acids. Native HZ was purified from infected RBCs by a series of centrifugation steps followed by organic extraction of its lipid coat. Analysis of the lipid coat revealed the presence of hydroxylated polyunsaturated fatty acids. These polar lipids were separated using reverse phase-, normal phase-, and chiral phase high performance liquid chromatography and subsequently examined by GC-MS. Native FIZ lipid coat GC-MS analysis revealed the presence of 15-, 12-, 11-, 9-, 8-, and 5-hydroxyeicosatetraenoic acids (HETEs) as well as 13- and 9-hydroxyoctadecadienoic acids (HODEs) (35). 

Liu B, Khan WA, Hannun YA, Timar J, Taylor JD, Lundy S, Butovich I, Honn KV. 12(S)hydroxyeicosatetraenoic acid and 13(S)-hydroxyoctadecadienoic acid regulation of protein kinase C-a in melanoma cells role of receptor-mediated hydrolysis of inositol phospholipids. Proc.Natl.Acad.Sci.U.S.A. 92 (1995) 9323-9327. 

Hydroxyoctadecadienoic acid (HODEs) Lipid peroxidation-related Linoleic GC/MS... 

Fig. 6. Comparative effects of 135-hydroxyoctadecadienoic acid (135-HODE) and 15S-hydroxyeicosatrienoic acid (155-HETrE). Abbreviation DHA, docosahexaenoic acid.

Fig. 8. Suppression of docosahexaenoic acid (DHA)-induced expression of epidermal nuclear mitogen-activated protein kinase (MARK) by 15-hydroxyeicosatrienoic acid (15-HETrE) and 135-hydroxyoctadecadienoic acid (13S-HODE).

Hydroxyoctadecadienoic Acid and 15-Hydroxyeicosa-trienoic Acid, Prostaglandins Leukot. Essent. Fatty Acids 62, 13 19. 

Kaduce, T. L., P. H. Figard et al. 1989. Formation of 9-hydroxyoctadecadienoic acid from linoleic acid in endothelial cells. J Biol Chem 264(12) 6823-6830. 

Shureiqi, L, K. J. Wojno et al. 1999. Decreased 13-S-hydroxyoctadecadienoic acid levels and 15-lipoxygenase-l expression in human colon cancers, 20(10) ... 

Enantiomerically pure (9/ )-HSA can be obtained from Dimorphoteca sinuata L. seed oil, a source of 10( ),12( )-(S)-9-hydroxyoctadecadienoic acid (dimorphecolic acid). [57] After transmethylation of the seed oil, followed by hydrogenation and hydrolysis, (9/ )-HSA can be obtained and the enantiomer with opposite configuration can be synthesized through stereospecific inversion of the chiral center. [55]... 

In addition to 8-DOX products, G. graminis or its cell-free extracts can metabolize a variety of fatty acids into oxylipins. Of those substrates, the most interesting are linoleic and oleic acids, which are common in ascomycetes. Linoleic acid gives rise to 16-hydroxyoctadecadienoic acid and 17-hydroxyoctadecadienoic acid via cyt P-450 activity. 8,16-Dihydroxyoctadecadienoic acid and 8,17-hydroxy-octadecadienoic acid were also produced, apparently by a combination of 8-DOX and cyt P-450 activity [6,16]. 

The hydroperoxidation products of linoleic acid were studied by Wu and coworkers [662]. Ten products (e.g., 13-hydroxy-(9Z-l l )-octadeca-9,l 1-dienoic acid, 9-hydroxy-(10 -12E)-octadeca-10,12-dienoic acid, ketooctadecadienoic acid, hydroxyoctadecadienoic acid) were resolved in <30 min on a silica column (2 =234nm) using a 98/2/0.05 hexane/IPA/acetic acid mobile phase. Peak shapes were excellent and good resolution was obtained. The same conditions were used in semipreparative work. Structures were confirmed by GC/MS. 

Seventeen hydroperoxy polyunsaturated fatty acids (e.g., 5-(5)-hydroperoxyeico-satetraenoic acid, 5-(S)-hydroperoxyeicosatetraenoic acid) were extracted from brain tissue and derivatized with acetic anhydride [1058]. The resulting solution was injected onto a Cjg column X = 235 nm) and eluted with a 15/8/2 acetonitrile/ water (0.1 M ammonium formate)/0.1 M formic acid mobile phase. The internal standard (12-hydroxyoctadecadienoic acid-rfg) was made up at the 600pmol level and stored in a solution containing BHT to prevent its oxidation. Thermospray MS was also used as a detector and was most sensitive when a 15/6/4 acetonitrile/0.1 M acetic acid/O.lM ammonium acetate mobile phase was used. In this example, detection limits of 0.1-0.5 pmol were obtained by single ion monitoring (SIM). 

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