(±)13-HODE

(±)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.

(±)13-HODE (13-hydroxyoctadecadienoic acid)是13(S)-HODE和13(R)-HODE的外消旋混合物，由亚油酸通过脂氧合酶或环氧化酶氧化生成^[1]。(±)13-HODE在生物系统中发挥着多种作用。(±)13-HODE可以调节促炎和抗炎细胞因子的产生，作用于巨噬细胞和淋巴细胞等免疫细胞并影响细胞的激活和功能^[2]。(±)13-HODE可诱导活性氧（ROS）的产生，还可以上调抗氧化防御机制^[3]。(±)13-HODE可以与特定受体或细胞内信号通路相互作用，(±)13-HODE可激活蛋白激酶C（PKC）通路，影响细胞增殖、分化和凋亡^[4]。

在体外，(±)13-HODE（20-50µM）处理人脐静脉内皮细胞（HUVEC）24小时，(±)13-HODE增加了细胞间黏附分子-1（ICAM-1）的表达，但对血管细胞黏附分子-1（VCAM-1）和E-选择素的表达无显著影响^[5]。在体外，MDA-MB-231细胞被处理为FABP7过表达（231-FABP7）和对照（231-RFP）两组，分别用12.5mM亚油酸（linoleic acid）或载体（vehicle）处理72小时，当向亚油酸处理的231-FABP7细胞中添加25nM (±)13-HODE时，细胞死亡现象得到显著缓解^[6]。

在体内实验中，以8mg的(±)13-HODE喂养低密度脂蛋白受体敲除（LDL receptor knockout）小鼠13周，(±)13-HODE导致小鼠主动脉病变面积增加了超过100%。(±)13-HODE了小鼠增加血浆总胆固醇和低密度脂蛋白胆固醇，并增加氧化应激^[7]。