...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Role of protein kinase C isoforms in bile formation and cholestasis
【24h】

Role of protein kinase C isoforms in bile formation and cholestasis

机译：蛋白激酶C同工型在胆汁形成和胆汁淤积中的作用

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

Transhepatic solute transport provides the osmotic driving force for canalicular bile formation. Choleretic and cholestatic agents affect bile formation, in part, by altering plasma membrane localizations of transporters involved in bile formation. These short-term dynamic changes in transporter location are highly regulated posttranslational events requiring various cellular signaling pathways. Interestingly, both choleretic and cholestatic agents activate the same intracellular signaling kinases, such as phosphoinositide-3-kinase (PI3K), protein kinase C (PKC), and mitogen-activated protein kinase (MAPK). An emerging theme is that choleretic and cholestatic effects may be mediated by different isoforms of these kinases. This is most evident for PKC-mediated regulation of plasma membrane localization of Na+-taurocholate cotransporting polypeptide (NTCP) and multidrug resistance-associated protein 2 (MRP2) by conventional PKCα (cPKCα), novel PKCδ (nPKCδ), nPKCε, and atypical PKCζ (aPKCζ). aPKCζ may mediate choleretic effects by inserting NTCP into the plasma membrane, and nPKCε may mediate cholestatic effects by retrieving MRP2 from the plasma membrane. On the other hand, cPKCα and nPKCδ may be involved in choleretic, cholestatic, and anticholestatic effects by inserting, retrieving, and inhibiting retrieval of transporters, respectively. The effects of PKC isoforms may be mediated by phosphorylation of the transporters, actin binding proteins (radixin and myristoylated alanine-rich C kinase substrate), and Rab proteins. Human NTCP plays an important role in the entry of hepatitis B and D viruses into hepatocytes and consequent infection. Thus, PKCs, by regulating NTCP trafficking, may also play an important role in hepatic viral infections.
机译：经肝溶质转运为小管胆汁的形成提供了渗透驱动力。胆汁和胆汁淤积剂部分地通过改变参与胆汁形成的转运蛋白的质膜定位来影响胆汁形成。转运蛋白位置的这些短期动态变化是高度调控的翻译后事件，需要各种细胞信号通路。有趣的是，胆汁和胆汁淤积剂均激活相同的细胞内信号激酶，例如磷酸肌醇-3-激酶（PI3K），蛋白激酶C（PKC）和促分裂原活化蛋白激酶（MAPK）。一个新兴的主题是，胆汁淤积和胆汁淤积效应可能是由这些激酶的不同同工型介导的。这对于常规PKCα（cPKCα），新型PKCδ（nPKCδ），nPKCε和非典型PKCζ对PKC介导的Na +-牛磺胆酸盐共转运多肽（NTCP）和多药耐药相关蛋白2（MRP2）的质膜定位的调节最为明显。 （aPKCζ）。 aPKCζ可通过将NTCP插入质膜来介导胆汁作用，而nPKCε可通过从质膜上检索MRP2来介导胆汁抑制作用。另一方面，cPKCα和nPKCδ可能分别通过插入，回收和抑制转运蛋白而参与了胆汁淤积，胆汁淤积和抗胆汁淤积的作用。 PKC同工型的作用可以通过转运蛋白，肌动蛋白结合蛋白（辐射蛋白和富含肉豆蔻基的富含丙氨酸的C激酶底物）和Rab蛋白的磷酸化来介导。人类NTCP在乙型和丁型肝炎病毒进入肝细胞以及随后的感染中起着重要作用。因此，通过调节NTCP的运输，PKCs在肝病毒感染中也可能起重要作用。

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