| Reference | [1]. Wien Klin Wochenschr. 1991;103(14):416-21.<br />
13-Hydroxyoctadecadienoic acid (13-HODE) metabolism and endothelial cell adhesion molecule expression: effect on platelet vessel wall adhesion.<br />
Buchanan MR(1), Bertomeu MC, Brister SJ, Haas TA.<br />
Author information: (1)Department of Pathology, McMaster University, Hamilton, Ontario, Canada.<br />
Endothelial cells synthesize two important fatty acid metabolites, PGI2, which is synthesized from arachidonic acid via the cyclooxygenase pathway, and 13-HODE, which is synthesized from linoleic acid via the lipoxygenase pathway. PGI2 is synthesized following cell activation or injury while 13-HODE is synthesized in the unstimulated cell. While the role of PGI2 in platelet vessel wall interactions has been studied extensively, the role of 13-HODE in platelet vessel wall interactions is just now being understood. The present evidence suggests that 13-HODE is continuously synthesized in "resting" vessel wall cells and is in close juxtaposition with the ubiquous integrin adhesion molecule, the vitronectin receptor. The observation that the endothelial cell is not adhesive when 13-HODE and the vitronectin receptor are in close association and becomes adhesive when these two moieties dissociate and the vitronectin receptor relocates on the surface of the cell, provides further evidence that 13-HODE may induce conformational changes in the vitronectin receptor to reduce its ability to recognize its adhesive ligands. The additional observations that 13-HODE levels in both human and animal vessel walls are inversely related with vessel wall adhesivity, and that this adhesivity can be altered by altering 13-HODE synthesis, provides evidence that 13-HODE down-regulates the thrombogenecity of the injured vessel wall surface.<br />
PMID: 1718092<br />
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[2]. Sci Rep. 2017 Aug 21;7(1):8976. doi: 10.1038/s41598-017-02759-0.<br />
Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice.<br />
Zhang W(1), Zhong W(1), Sun Q(1), Sun X(1), Zhou Z(2)(3).<br />
Author information: (1)Center for Translational Biomedical Research, University of North Carolina Greensboro, North Carolina Research Campus, Kannapolis, NC, 28081, USA. (2)Center for Translational Biomedical Research, University of North Carolina Greensboro, North Carolina Research Campus, Kannapolis, NC, 28081, USA. [email protected]. (3)Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC, 28081, USA. [email protected].<br />
Chronic alcohol feeding causes lipid accumulation and apoptosis in the liver. This study investigated the role of bioactive lipid metabolites in alcohol-induced liver damage and tested the potential of targeting arachidonate 15-lipoxygenase (ALOX15) in treating alcoholic liver disease (ALD). Results showed that chronic alcohol exposure induced hepatocyte apoptosis in association with increased hepatic 13-HODE. Exposure of 13-HODE to Hepa-1c1c7 cells induced oxidative stress, ER stress and apoptosis. 13-HODE also perturbed proteins related to lipid metabolism. HODE-generating ALOX15 was up-regulated by chronic alcohol exposure. Linoleic acid, but not ethanol or acetaldehyde, induced ALOX15 expression in Hepa-1c1c7 cells. ALOX15 knockout prevented alcohol-induced liver damage via attenuation of oxidative stress, ER stress, lipid metabolic disorder, and cell death signaling. ALOX15 inhibitor (PD146176) treatment also significantly alleviated alcohol-induced oxidative stress, lipid accumulation and liver damage. These results demonstrated that activation of ALOX15/13-HODE circuit critically mediates the pathogenesis of ALD. This study suggests that ALOX15 is a potential molecular target for treatment of ALD.<br />
DOI: 10.1038/s41598-017-02759-0 PMCID: PMC5567196 PMID: 28827690<br />
Conflict of interest statement: The authors declare that they have no competing interests.<br />
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[3]. Adv Exp Med Biol. 1997;433:291-4. doi: 10.1007/978-1-4899-1810-9_61.<br />
The importance of linoleic acid metabolites in cancer metastasis and in the synthesis and actions of 13-HODE.<br />
Horrobin DF(1), Ziboh VA.<br />
Author information: (1)Scotia Research Institute, Stirling, Scotland.<br />
Large scale human epidemiological studies indicate that high intakes of linoleic acid protect against the development of cancer. One mechanism may be the generation of 13-HODE from linoleic acid. 13-HODE prevents cell adhesion to endothelial cells and can inhibit cancer metastasis. 13-HODE synthesis is enhanced by cyclic AMP. Gamma-linolenic acid, a desaturated metabolite of linoleic acid, causes substantial stimulation of 13-HODE synthesis. A fall in gamma-linolenic acid synthesis with age may be related to the age-related fall in 13-HODE formation.<br />
DOI: 10.1007/978-1-4899-1810-9_61 PMID: 9561154<br />
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[4]. Prostaglandins Leukot Essent Fatty Acids. 1990 Feb;39(2):125-9. doi: 10.1016/0952-3278(90)90021-c.<br />
Quantitation of 13-hydroxyoctadecadienoic acid (13-HODE) by radioimmunoassay.<br />
Tonogai Y(1), Tai HH.<br />
Author information: (1)Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Kentucky, Lexington 40536-0082.<br />
Antibodies against 13-hydroxyoctadecadienoic acid (13-HODE) were produced in rabbits by immunizing the animal with 13-HODE-thyroglobulin conjugate. The antibodies appeared to be rather specific for 13-HODE since other hydroxy fatty acids showed minimal crossreaction. The radioimmunoassay was capable of detecting 50 pg per assay tube and was applied to the study of the biosynthesis of 13-HODE in platelets and leukocytes. In contrast to reported findings from endothelial cells, A-23187, thrombin and collagen stimulated synthesis and release of 13-HODE from platelets. However, insignificant synthesis of 13-HODE was found in leukocytes following A-23187 stimulation. Exogenous addition of linoleic acid stimulated the synthesis of 13-HODE from both platelets and leukocytes. The majority of 13-HODE synthesized was found in the medium. These studies suggest that both types of blood cells possess active (omega-6) lipoxygenase. Platelets may use endogenously released linoleic acid to synthesize 13-HODE, whereas leukocytes may utilize linoleic acid released from other cell types for 13-HODE synthesis.<br />
DOI: 10.1016/0952-3278(90)90021-c PMID: 2111553<br />
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[5]. J Lipid Res. 1999 Apr;40(4):699-707.<br />
13-(S)-hydroxyoctadecadienoic acid (13-HODE) incorporation and conversion to novel products by endothelial cells.<br />
Fang X(1), Kaduce TL, Spector AA.<br />
Author information: (1)Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA.<br />
13(S)-Hydroxy-[12,13-3H]octadecadienoic acid (13-HODE), a linoleic acid oxidation product that has vasoactive properties, was rapidly taken up by bovine aortic endothelial cells. Most of the 13-HODE was incorporated into phosphatidylcholine, and 80% was present in the sn -2 position. The amount of 13-HODE retained in the cells gradually decreased, and radiolabeled metabolites with shorter reverse-phase high-performance liquid chromatography retention times (RT) than 13-HODE accumulated in the extracellular fluid. The three major metabolites were identified by gas chromatography combined with mass spectrometry as 11-hydroxyhexadecadienoic acid (11-OH-16:2), 9-hydroxytetradecadienoic acid (9-OH-14:2), and 7-hydroxydodecadienoic acid (7-OH-12:2). Most of the radioactivity contained in the cell lipids remained as 13-HODE. However, some 11-OH-16:2 and several unidentified products with longer RT than 13-HODE were detected in the cell lipids. Normal human skin fibroblasts also converted 13-HODE to the three major chain-shortened metabolites, but Zellweger syndrome fibroblasts produced only a very small amount of 11-OH-16:2. Therefore, the chain-shortened products probably are formed primarily by peroxisomal beta-oxidation. These findings suggest that peroxisomal beta-oxidation may constitute a mechanism for the inactivation and removal of 13-HODE from the vascular wall. Because this is a gradual process, some 13-HODE that is initially incorporated remains in endothelial phospholipids, especially phosphatidylcholine. This may be the cause of some of the functional perturbations produced by 13-HODE in the vascular wall.<br />
PMID: 10191294
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