人类巨噬细胞中START脂质转运蛋白STARD1亚家族的差异调节
Differential regulation of the STARD1 subfamily of START lipid trafficking proteins in human macrophages.
作者信息
Borthwick Faye, Taylor Janice M, Bartholomew Chris, Graham Annette
机构信息
Vascular Biology Group, Glasgow Caledonian University, Glasgow, UK.
出版信息
FEBS Lett. 2009 Apr 2;583(7):1147-53. doi: 10.1016/j.febslet.2009.02.042. Epub 2009 Mar 10.
The STARD1 subfamily of 'START' lipid trafficking proteins can reduce macrophage lipid content and inflammatory status (STARD1; StAR), and traffic cholesterol from endosomes (STARD3/MLN64). During macrophage differentiation, STARD1 mRNA and protein increase with sterol content, while the reverse is true for STARD3. Sterol depletion (methyl beta-cyclodextrin) enhances STARD3, and represses STARD1 expression. Agonists of Liver X receptors, peroxisome proliferator activated receptor-gamma and retinoic acid X receptors increase STARD1 expression, while hypocholesterolaemic agent, LY295427, reveals both STARD1 and STARD3 as putative SREBP-target genes. Pathophysiological 'foam cell' formation, induced by acetylated or oxidized LDL, significantly reduced both STARD1 and STARD3 gene expression. Differential regulation of STARD1 and D3 reflects their distinct roles in macrophage cholesterol metabolism, and may inform anti-atherogenic strategies.
“START”脂质转运蛋白的STARD1亚家族可降低巨噬细胞脂质含量和炎症状态（STARD1；类固醇生成急性调节蛋白），并从内体转运胆固醇（STARD3/MLN64）。在巨噬细胞分化过程中，STARD1的mRNA和蛋白随固醇含量增加，而STARD3则相反。固醇耗竭（甲基-β-环糊精）增强STARD3，并抑制STARD1表达。肝脏X受体、过氧化物酶体增殖物激活受体-γ和视黄酸X受体的激动剂增加STARD1表达，而降胆固醇药物LY295427显示STARD1和STARD3均为假定的固醇调节元件结合蛋白靶基因。由乙酰化或氧化低密度脂蛋白诱导的病理生理“泡沫细胞”形成显著降低了STARD1和STARD3基因表达。STARD1和STARD3的差异调节反映了它们在巨噬细胞胆固醇代谢中的不同作用，并可能为抗动脉粥样硬化策略提供依据。
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