Olivier Maryline, BottG Remain, Frisdal Eric, Nowick Marion, Plengpanich Wanee, Desmarchelier Charles, Roi Stéphanie, Quinn Carmel M, Gelissen Ingrid, Jessup Wendy, Van Eck Miranda, Guérin Maryse, Le Goff Wilfried, Reboul Emmanuelle
Biochim Biophys Acta. 2014 Dec;1841(12):1741-51. doi: 10.1016/j.bbalip.2014.10.003.
Vitamin E membrane transport has been shown to involve the cholesterol transporters SR-BI, ABCA1 and NPC1L1. Our aim was to investigate the possible participation of another cholesterol transporter in cellular vitamin E efflux: ABCG1. In Abcgl-deficient mice, vitamin E concentration was reduced in plasma lipoproteins whereas most tissues displayed a higher vitamin E content compared to wild-type mice. α- and γ-tocopherol efflux was increased in CHO cells overexpressing human ABCG1 compared to control cells. Conversely, α- and γ- tocopherol efflux was decreased in ABCG1-knockdown human cells (Hep3B hepatocytes and THP-1 macro- phages). Interestingly, α- and γ-tocopherol significantly downregulated ABCG1 and ABCA1 expression levels in Hep3B and THP-1, an effect confirmed in vivo in rats given vitamin E for 5 days. This was likely due to reduced LXR activation by oxysterols, as Hep3B cells and rat liver treated with vitamin E displayed a significantly reduced content in oxysterols compared to their respective controls. Overall, the present study reveals for the first time that ABCG1 is involved in cellular vitamin E efflux.
维生素E的膜转运已被证明涉及胆固醇转运蛋白SR-BI、ABCA1和NPC1L1。我们的目的是研究另一种胆固醇转运蛋白ABCG1在细胞维生素E外排中的可能作用。在Abcgl基因缺陷小鼠中，血浆脂蛋白中的维生素E浓度降低，而与野生型小鼠相比，大多数组织的维生素E含量更高。与对照细胞相比，过表达人ABCG1的CHO细胞中α-和γ-生育酚的外排增加。相反，在ABCG1基因敲低的人细胞（Hep3B肝细胞和THP-1巨噬细胞）中，α-和γ-生育酚的外排减少。有趣的是，α-和γ-生育酚显著下调了Hep3B和THP-1细胞中ABCG1和ABCA1的表达水平，在给大鼠喂食维生素E 5天的体内实验中也证实了这一效应。这可能是由于氧化甾醇对肝X受体（LXR）的激活作用减弱，因为与各自的对照相比，用维生素E处理的Hep3B细胞和大鼠肝脏中的氧化甾醇含量显著降低。总体而言，本研究首次揭示ABCG1参与细胞维生素E外排。
