有机溶质转运蛋白OSTalpha/ β在非酒精性脂肪性肝炎中过表达，并被与肝损伤相关的药物调节。
文章的细节
-
引用
复制到剪贴板 -
马利宁MM，阿里I，贝赞松J，博杜安JJ，布劳维尔KLR
有机溶质转运蛋白OSTalpha/ β在非酒精性脂肪性肝炎中过表达，并被与肝损伤相关的药物调节。
美国医学杂志。2018年5月1日;314(5):G597-G609。doi: 10.1152 / ajpgi.00310.2017。Epub 2018 2月8日。
- PubMed ID
-
29420067 (PubMed视图］
- 摘要
-
异构体类固醇转运蛋白有机溶质转运蛋白α / β (OSTalpha/ β， SLC51A/B)在十多年前被发现，但其在肝脏中的生理意义仍不确定。一个主要的挑战是缺乏合适的表达OSTalpha/beta的模型。基于本文首次报道的非酒精性脂肪性肝炎中肝脏OSTalpha/ β上调的观察结果，本研究的目的是建立一个体外模型来评估OSTalpha/ β功能及其与药物和胆汁酸的相互作用。必威国际app通过定量RT-PCR、Western blotting和免疫荧光分析人肝组织OSTalpha/beta的表达。在建立的体外模型中，使用放射性标记化合物来确定OSTalpha/ β介导的转运。评估了胆汁酸和药物(包括与胆汁淤积性药物性肝损伤相关的药物)对OSTalpha/ β介导的转运的影响。非酒精性脂肪性肝炎和原发性胆道胆管炎患者肝脏中OSTalpha/ β表达升高，而对照组肝组织中OSTalpha/ β表达低。在基于细胞的新系统中的研究表明，所有测试化合物:硫酸脱氢表雄酮、地高辛、硫酸雌酮和牛磺胆酸酯的OSTalpha/ β介导的快速线性转运。与26种化合物的相互作用研究揭示了新的OSTalpha/ β抑制剂:一种胆汁淤积的生物标志物，糖chenodeoxycholic acid;曲格列酮的主要代谢产物为硫酸曲格列酮; and a macrocyclic antibiotic, fidaxomicin. Additionally, some drugs (e.g., digoxin) consistently stimulated taurocholate uptake in OSTalpha/beta-overexpressing cells. Our findings demonstrate that OSTalpha/beta is an important transporter in liver disease and imply a role for this transporter in bile acid-bile acid and drug-bile acid interactions, as well as cholestatic drug-induced liver injury. NEW & NOTEWORTHY The organic solute transporter OSTalpha/beta is highly expressed in hepatocytes of liver tissue obtained from patients with nonalcoholic steatohepatitis and primary biliary cholangitis. OSTalpha/beta substrates exhibit rapid, linear, and concentration-driven transport in an OSTalpha/beta-overexpressing cell line. Drugs associated with hepatotoxicity modulate OSTalpha/beta-mediated taurocholate transport. These data suggest that hepatic OSTalpha/beta plays an essential role in patients with cholestasis and may have important clinical implications for bile acid and drug disposition.