(±)13-HODE (13-hydroxyoctadecadienoic acid) is a racemic mixture of 13(S)-HODE and 13(R)-HODE, which is formed through the oxidation of linoleic acid by lipoxygenases or cyclooxygenases[1]. (±)13-HODE plays diverse roles in biological systems. In inflammation, (±)13-HODE can modulate the production of pro-and anti-inflammatory cytokines. (±)13-HODE can act on immune cells such as macrophages and lymphocytes, influencing their activation and function[2]. (±)13-HODE can either contribute to or alleviate oxidative damage depending on the cellular context. (±)13-HODE may induce the generation of reactive oxygen species (ROS), (±)13-HODE can upregulate antioxidant defense mechanisms[3]. (±)13-HODE can interact with specific receptors or intracellular signaling pathways. (±)13-HODE may activate protein kinase C (PKC) pathways, affecting cell proliferation, differentiation, and apoptosis[4].
In vitro, treatment of human umbilical vein endothelial cells (HUVEC) with (±)13-HODE (20-50µM) for 24 hours increased the expression of intercellular adhesion molecule-1 (ICAM-1), but had no significant effect on the expression of vascular cell adhesion molecule-1 (VCAM-1) and E-selectin[5]. In vitro, MDA-MB-231 cells were divided into two groups: FABP7-overexpressing cells (231-FABP7) and control cells (231-RFP). Both groups were treated with 12.5mM linoleic acid or vehicle for 72 hours. When 25nM (±)13-HODE was added to the linoleic acid-treated 231-FABP7 cells, the cell death was significantly alleviated[6].
In vivo, (±)13-HODE was administered at a dose of 8mg to low-density lipoprotein receptor knockout (LDL receptor knockout) mice for 13 weeks. (±)13-HODE led to an increase of over 100% in the aortic lesion area of the mice. (±)13-HODE also increased plasma total cholesterol and low-density lipoprotein cholesterol in the mice and enhanced oxidative stress[7].
References:
[1] Brash AR. Lipoxygenases: occurrence, functions, catalysis, and acquisition of substrate. J Biol Chem. 1999 Aug 20;274(34):23679-82.
[2] Serhan CN, Petasis NA. Resolvins and protectins in inflammation resolution. Chem Rev. 2011 Oct 12;111(10):5922-43.
[3] Buchanan MR, Horsewood P, Brister SJ. Regulation of endothelial cell and platelet receptor-ligand binding by the 12- and 15-lipoxygenase monohydroxides, 12-, 15-HETE and 13-HODE. Prostaglandins Leukot Essent Fatty Acids. 1998 May;58(5):339-46.
[4] Nishizuka Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science. 1992 Oct 23;258(5082):607-14.
[5] Friedrichs B, Toborek M, Hennig B, et al. 13-HPODE and 13-HODE modulate cytokine-induced expression of endothelial cell adhesion molecules differently. Biofactors. 1999;9(1):61-72.
[6] Kwong SC, Abd Jamil AH, Rhodes A, et al. Fatty acid binding protein 7 mediates linoleic acid-induced cell death in triple negative breast cancer cells by modulating 13-HODE. Biochimie. 2020 Dec;179:23-31.
[7] Khan-Merchant N, Penumetcha M, Meilhac O, et al. Oxidized fatty acids promote atherosclerosis only in the presence of dietary cholesterol in low-density lipoprotein receptor knockout mice. J Nutr. 2002 Nov;132(11):3256-62.