Regulation of hepatic bile acid transporters Ntcp and Bsep expression
Regulation of hepatic bile acid transporters Ntcp and Bsep expression
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DOI：
10.1016/j.bcp.2007.08.014
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发表时间：
2007-12-03
影响因子：
5.8
通讯作者：
Klaassen, Curtis D.
中科院分区：
文献类型：
--
作者：
Cheng, Xinqquo;Buckley, David;Klaassen, Curtis D.
牛磺胆酸钠共转运多肽（Ntcp）和胆盐输出泵（Bsep）是肝脏摄取和排泄胆汁酸的两个关键转运蛋白。在病理生理条件下，已报道了Ntcp和Bsep表达的改变。在本研究中，年龄，性别和各种化学物质对这两种转运蛋白的调节的影响在小鼠中进行了表征。Ntcp和Bsep mRNA在小鼠肝脏中的表达水平在胎儿期较低，但在分娩时增加至最高表达。出生后，小鼠Ntcp和Bsep mRNA下降超过50%，然后逐渐增加到成人水平的第30天。小鼠Ntcp mRNA和蛋白的表达在雌性肝脏中比雄性肝脏中表现出更高的水平。在人类和小鼠肝脏中BSEP/Bsep表达不存在性别差异。在性腺切除、垂体切除和lit/lit小鼠中进行的激素替代表明，小鼠肝脏中雌性主导的Ntcp表达是由于雄性模式GH分泌的抑制作用，而不是性激素。Ntcp和Bsep表达通常对大量微粒体酶诱导剂的诱导具有抗性。给药消胆胺增加Ntcp，而鹅去氧胆酸（CDCA）增加Bsep mRNA的表达。总之，小鼠Ntcp和Bsep受年龄、性别、消胆胺和胆汁酸的调节，但对大多数微粒体酶诱导剂的诱导具有抗性。(c)2007爱思唯尔公司All rights reserved.
Sodium-taurocholate cotransporting polypeptide (Ntcp) and bile salt export pump (Bsep) are two key transporters for hepatic bile acid uptake and excretion. Alterations in Ntcp and Bsep expression have been reported in pathophysiological conditions. In the present study, the effects of age, gender, and various chemicals on the regulation of these two transporters were characterized in mice. Ntcp and Bsep mRNA levels in mouse liver were low in the fetus, but increased to its highest expression at parturition. After birth, mouse Ntcp and Bsep mRNA decreased by more than 50%, and then gradually increased to adult levels by day 30. Expression of mouse Ntcp mRNA and protein exhibit higher levels in female than male livers. No gender difference exists in BSEP/Bsep expression in human and mouse livers, Hormone replacements conducted in gonadectomized, hypophysectomized, and lit/lit mice indicate that female-predominant Ntcp expression in mouse liver is due to the inhibitory effect of male-pattern GH secretion, but not sex hormones. Ntcp and Bsep expression are in general resistant to induction by a large battery of microsomal enzyme inducers. Administration of cholestyramine increased Ntcp, whereas chenodeoxycholic acid (CDCA) increased Bsep mRNA expression. In conclusion, mouse Ntcp and Bsep are regulated by age, gender, cholestyramine, and bile acid, but resistant to induction by most microsomal enzyme inducers. (c) 2007 Elsevier Inc. All rights reserved.