Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 26-32, 35390 Giessen, Germany.
Lipids Health Dis. 2011 Nov 30;10:222. doi: 10.1186/1476-511X-10-222.
Synthetic activators of peroxisome proliferator-activated receptors (PPARs) stimulate cholesterol removal from macrophages through PPAR-dependent up-regulation of liver × receptor α (LXRα) and subsequent induction of cholesterol exporters such as ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type 1 (SR-BI). The present study aimed to test the hypothesis that the hydroxylated derivative of linoleic acid (LA), 13-HODE, which is a natural PPAR agonist, has similar effects in RAW264.7 macrophages.
RAW264.7 macrophages were treated without (control) or with LA or 13-HODE in the presence and absence of PPARα or PPARγ antagonists and determined protein levels of LXRα, ABCA1, ABCG1, SR-BI, PPARα and PPARγ and apolipoprotein A-I mediated lipid efflux.
Treatment of RAW264.7 cells with 13-HODE increased PPAR-transactivation activity and protein concentrations of LXRα, ABCA1, ABCG1 and SR-BI when compared to control treatment (P < 0.05). In addition, 13-HODE enhanced cholesterol concentration in the medium but decreased cellular cholesterol concentration during incubation of cells with the extracellular lipid acceptor apolipoprotein A-I (P < 0.05). Pre-treatment of cells with a selective PPARα or PPARγ antagonist completely abolished the effects of 13-HODE on cholesterol efflux and protein levels of genes investigated. In contrast to 13-HODE, LA had no effect on either of these parameters compared to control cells.
13-HODE induces cholesterol efflux from macrophages via the PPAR-LXRα-ABCA1/SR-BI-pathway.
过氧化物酶体增殖物激活受体（PPARs）的合成激活剂通过 PPAR 依赖性上调肝 X 受体 α（LXRα）并随后诱导胆固醇外排体，如 ATP 结合盒转运体 A1（ABCA1）和清道夫受体 B 类 1 型（SR-BI），从巨噬细胞中去除胆固醇。本研究旨在测试假设，即亚油酸（LA）的羟化衍生物 13-HODE，一种天然的 PPAR 激动剂，在 RAW264.7 巨噬细胞中具有类似的作用。
RAW264.7 巨噬细胞在没有（对照）或存在和不存在 PPARα 或 PPARγ 拮抗剂的情况下用 LA 或 13-HODE 处理，并测定 LXRα、ABCA1、ABCG1、SR-BI、PPARα 和 PPARγ 的蛋白水平以及载脂蛋白 A-I 介导的脂质外排。
与对照处理相比，13-HODE 处理 RAW264.7 细胞增加了 PPAR 转激活活性和 LXRα、ABCA1、ABCG1 和 SR-BI 的蛋白浓度（P < 0.05）。此外，13-HODE 增加了培养基中的胆固醇浓度，但在细胞与细胞外脂质受体载脂蛋白 A-I 孵育期间降低了细胞内胆固醇浓度（P < 0.05）。用选择性 PPARα 或 PPARγ 拮抗剂预处理细胞完全消除了 13-HODE 对胆固醇外排和所研究基因的蛋白水平的影响。与 13-HODE 相比，LA 与对照细胞相比对这些参数均无影响。
13-HODE 通过 PPAR-LXRα-ABCA1/SR-BI 通路诱导巨噬细胞中的胆固醇外排。
