• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >OATP1B3-1B7, a novel organic anion transporting polypeptide, is modulated by FXR ligands and transports bile acids.
【24h】

OATP1B3-1B7, a novel organic anion transporting polypeptide, is modulated by FXR ligands and transports bile acids.

机译：新型有机阴离子输送多肽，通过FXR配体调节oATP1B3-1B7并转运胆汁酸。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Organic anion transporting polypeptide (OATP) 1B3-1B7 (LST-3TM12) is a member of the OATP1B [solute earner organic anion transporter (SLCO) IB] family. This transporter is not only functional but also expressed in the membrane of the smooth endoplasmic reticulum of hepatocytes and enterocytes. OATP1B3-1B7 is a splice variant of SLCO1B3 in which the initial part is encoded by SLCO1B3, whereas the rest of the mRNA originates from the gene locus of SLCO1B7. In this study, we not only showed that SLCO1B3 and the mRNA encoding for OATP1B3-1B7 share the 5' untranslated region but also that silencing of an initial SLCO1B3 exon lowered the amount of SLCO1B3 and of SLCOJB7 mRNA in Huh-7 cells. To validate the assumption that both transcripts are regulated by the same promoter we tested the influence of the bile acid sensor farnesoid X receptor (FXR) on their transcription. Treatment of Huh-7 and HepaRG cells with activators of this known regulator of OATP1B3 not only increased SLCO1B3 but also OATP1B3-1B7 mRNA transcription. Applying a heterologous expression system, we showed that several bile acids interact with OATP1B3-1B7 and that taurocholic acid and lithocholic acid are OATP1B3-1B7 substrates. As OATP1B3-1B7 is located in the smooth endoplasmic reticulum, it may grant access to metabolizing enzymes. In accordance are our findings showing that the OATP1B3-1B7 inhibitor bromsulphthalein significantly reduced uptake of bile acids into human liver microsomes. Taken together, we report that OATP1B3-1B7 transcription can be modulated with FXR agonists and antagonists and that OATP1B3-1B7 transports bile acids. NEW & NOTEWORTHY Our study on the transcriptional regulation of the novel organic anion transporting polypeptide (OATP) 1B3-1B7 concludes that the promoter of solute carrier organic anion transporter (SLCO) 1B3 governs SLCO1B3-1B7 transcription. Moreover, the transcription of OATP1B3-1B7 can be modulated by farnesoid X receptor (FXR) agonists and antagonists. FXR is a major regulator in bile acid homeostasis that links OATP1B3-1B7 to this physiological function. Findings in transport studies with OATP1B3-1B7 suggest that this transporter interacts with the herein tested bile acids.
机译：有机阴离子输送多肽（OATP）1B3-1B7（LST-3TM12）是oatp1b [溶质溶剂有机阴离子转运蛋白（SLCO）IB]的成员。该转运蛋白不仅具有功能性，而且在肝细胞和肠细胞的光滑内质网的膜中表达。 OATP1B3-1B7是SLCO1B3的剪接变型，其中初始部分由SLCO1B3编码，而MRNA的其余部分来自SLCO1B7的基因座。在这项研究中，我们不仅表明SLCO1B3和OATP1B3-1B7的MRNA编码共享5'未转换区域，而且还使初始SLCO1B3外显子的沉默降低了HUH-7细胞中的SLCO1B3和SLCOJB7 mRNA的量。为了验证两种转录物由相同启动子调节的假设，我们测试了胆汁酸传感器法呢X受体（FXR）对其转录的影响。用这种已知的oaTP1b3调节剂的活化剂处理Huh-7和肝细胞的处理不仅增加了SLCO1B3，而且还增加了OATP1B3-1B7 mRNA转录。施用异源表达系统，我们表明几个胆汁酸与oatp1b3-1b7相互作用，并且牛磺酸和锂色酸是oatp1b3-1b7基材。由于OATP1B3-1B7位于光滑的内质网中，它可以授予对代谢酶的访问。根据我们的研究结果表明，OATP1B3-1B7抑制剂Bromsulphthalein显着降低了胆汁酸的摄取到人肝微粒体中。我们一起携带，我们报告oatp1b3-1b7转录可以用fxr激动剂和拮抗剂调节，并且oatp1b3-1b7传输胆汁酸。新的和值得注意的是我们对新型有机阴离子输送多肽（OATP）1B3-1B7的转录调节的研究得出结论：溶质载体有机阴离子转运蛋白（SLCO）1B3的启动子治理SLCO1B3-1B7转录。此外，可以通过Farnesoid X受体（FXR）激动剂和拮抗剂来调节OATP1B3-1B7的转录。 FXR是胆汁酸稳态的主要调节因子，将oatp1b3-1b7与这种生理功能联系起来。通过oatp1b3-1b7的运输研究表明该转运蛋白与本文测试的胆汁酸相互作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

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