有机阴离子转运多肽活性及表达调控的影响因素

Regulation of organic anion transporting polypeptides expression and activity

有机阴离子转运多肽(organic anion transporting polypeptides,OATP)是一类重要的跨膜摄取转运体,属于溶质转运体(solute carrier,SLC)超家族,以Na+和ATP非依赖方式参与内源物(胆汁酸、胆红素、前列腺素、甲状腺激素和甾体激素结合物)、药物及毒物转运。多种因素(如激素、炎症因子和药物等)会影响OATP的分布、表达及活性,引起底物在组织器官内蓄积的改变,导致食物-药物及药物-药物相互作用。癌组织内OATP分布特性及表达变化可能参与肿瘤的病理过程。表观基因组学调节与OATP的特异性分布有关。本文就参与OATP表达及功能调控的因素进行综述,为药物研发及发病机制的阐明提供线索。

Organic anion transporting polypeptides（OATP）, a member of solute carrier（SLC） superfamily, is considered as an important transmembrane uptake transporters. OATP is involved in the transport of a variety of endo- and xenobiotics（bile acids, bilirubin, prostaglandin, thyroid hormones, steroid hormone conjugates）, drugs and toxins in a Na＋ and ATP independent manner. Multiple factors（eg. hormones, proinflammatory cytokines, drugs） can affect the distribution, expression and activity of OATPs, leading to an altered accumulation of OATP substrates and related food-drug and drug-drug interactions. Changes in the distribution and expression of OATPs in malignant tissues may be related to the pathological process of cancer, while the modulation epigenetic mechanism also contributes to its distribution patterns. This review describes the factors that can affect the expression or function of OATPs, which may provide a valuable reference for drug development and the clarification of pathogenesis.