• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>International Journal of Molecular Sciences >Apical Sodium-Dependent Bile Acid Cotransporter A Novel Transporter of Indocyanine Green and Its Application in Drug Screening
【2h】

Apical Sodium-Dependent Bile Acid Cotransporter A Novel Transporter of Indocyanine Green and Its Application in Drug Screening

机译：根尖钠依赖性胆汁酸共转运蛋白一种新型的吲哚菁绿转运蛋白及其在药物筛选中的应用

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Bile acid plays critical roles in the elimination of inorganic compounds such as bilirubin, heavy metals, and drug metabolites. Apical sodium-dependent bile acid cotransporter (ASBT), a solute carrier membrane transport protein, transports bile acids. Several inhibitors of ASBT have been evaluated in clinical trials. Sodium taurocholate cotransporting polypeptide (NTCP), belonging to the same family as ASBT, has fluorescein 5(6)-isothiocyanate (FITC) and indocyanine green (ICG) transportability. ICG, a Food and Drug Administration-approved fluorophore at near-infrared range, has perfect optical characteristics, so it can be applied in cell tracking and drug screening. In this study, ASBT and NTCP were transduced into the HT-1080 cell line. Nude mice were subcutaneously xenografted with control and ASBT-expressing cells. ICG transportability was observed through flow cytometry, fluorescent microscopy, multi-mode plate readers, and an in vivo imaging system. Several molecules, including taurocholate, sodium deoxycholate, cyclosporine A, nifedipine, and Primovist, were used to evaluate an in vitro drug-screening platform by using the combination of ICG and ASBT through flow cytometry. ICG and FITC were validated and shown to be transported by ASBT. NTCP had a higher ICG intensity compared with ASBT. For cell tracking, the ASBT xenograft had similar ICG signals as the control. For a drug-screening platform, the ICG intensity decreased with 186 μM taurocholate (56.8%), deoxycholate (83.8%), and increased with nifedipine (133.2%). These findings are suggestive of opportunities for the high-throughput drug screening of cholestasis and other diseases that are related to the dynamics of bile acid reabsorption.
机译：胆汁酸在消除诸如胆红素，重金属和药物代谢产物等无机化合物中起关键作用。根尖钠依赖性胆汁酸共转运蛋白（ASBT），一种溶质载体膜转运蛋白，转运胆汁酸。在临床试验中已经评估了几种ASBT抑制剂。牛磺胆酸钠共转运多肽（NTCP）与ASBT属于同一家族，具有荧光素5（6）-异硫氰酸酯（FITC）和吲哚菁绿（ICG）的可运输性。 ICG是获得美国食品药品监督管理局（FDA）批准的近红外荧光团，具有理想的光学特性，因此可用于细胞跟踪和药物筛选。在这项研究中，ASBT和NTCP被转导到HT-1080细胞系中。裸鼠皮下移植有对照和表达ASBT的细胞。通过流式细胞仪，荧光显微镜，多模式读板器和体内成像系统观察到了ICG的运输性。通过流式细胞术结合使用ICG和ASBT，使用牛磺胆酸盐，脱氧胆酸钠，环孢菌素A，硝苯地平和Primovist等几种分子来评估体外药物筛选平台。 ICG和FITC已通过验证，并显示由ASBT运送。与ASBT相比，NTCP的ICG强度更高。对于细胞追踪，ASBT异种移植物具有与对照相似的ICG信号。对于药物筛选平台，ICG强度随着186μM牛磺胆酸盐（56.8％），脱氧胆酸盐（83.8％）而降低，而硝苯地平（133.2％）升高。这些发现提示对胆汁淤积症和其他与胆汁酸重吸收动力学有关的疾病进行高通量药物筛选的机会。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号