Regulation of the dynamic localization of the rat Bsep gene‐encoded bile salt export pump by anisoosmolarity
Regulation of the dynamic localization of the rat Bsep gene‐encoded bile salt export pump by anisoosmolarity
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不同渗透压对大鼠 Bsep 基因编码胆汁盐输出泵动态定位的调节
DOI：
10.1053/jhep.2001.22648
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发表时间：
2001
期刊：
影响因子：
13.5
通讯作者：
D. Häussinger
中科院分区：
文献类型：
--
作者：
M. Schmitt;R. Kubitz;S. Lizun;M. Wettstein;D. Häussinger
通过胆盐输出泵（Bsep）的小管转运代表了牛磺胆酸盐排泄的速率控制步骤，其容量受渗透压控制。通过免疫组织化学、共聚焦显微镜和光密度测定法，在灌注的大鼠肝脏中研究了等渗性和Ca 2+撤除对Bsep和紧密连接蛋白ZO-1和occludin定位的短期影响。在正常渗透压条件下，Bsep被发现在小管膜，并表现出点状细胞内定位。低渗透压导致细胞内Bsep易位到小管膜，而高渗透压诱导Bsep的检索。高渗性检索后Bsep和多药耐药蛋白2（Mrp 2）从小管膜，在推定的细胞内囊泡Bsep和Mrp 2共定位在这些囊泡的15%，而85%染色阳性Bsep（61%）或Mrp 2（24%）。非等渗性对occludin和Zo-1的线性染色模式没有影响，表明细胞旁渗透性没有增加。缺钙导致胆汁淤积，表现为occludin的破坏，而Zo‐1、Bsep和Mrp 2的定位不受影响。结论：（1）高渗可诱导Bsep从小管膜中回收，这与胆汁淤积相关。低渗导致胆汁分泌，伴随着细胞内Bsep快速募集到小管膜。(2)Bsep和Mrp 2特异性囊泡参与小管分泌的短期代谢调节，然而，胆盐排泄和转运蛋白定位之间的因果关系仍有待建立。(3)Ca 2+耗竭通过破坏occludin决定的紧密连接通透性诱导胆汁淤积，而小管转运蛋白的内化起次要作用。
Canalicular transport via the bile salt export pump (Bsep) represents the rate‐controlling step in taurocholate excretion, whose capacity is under osmotic control. The short‐term effects of anisoosmolarity and Ca2+‐withdrawal on the localization of Bsep and the tight junction proteins Zo‐1 and occludin were studied in perfused rat liver by immunohistochemistry, confocal microscopy, and densitometry. Under normoosmotic conditions, Bsep was found in the canalicular membrane and showed a punctate intracellular localization. Hypoosmolarity resulted in the translocation of intracellular Bsep to the canalicular membrane, whereas hyperosmolarity induced a retrieval of Bsep. Following hyperosmolar retrieval of Bsep and multidrug resistance protein 2 (Mrp2) from the canalicular membrane, in the putative intracellular vesicles Bsep and Mrp2 colocalized in 15% of these vesicles, whereas 85% stained either positive for Bsep (61%) or Mrp2 (24%). Anisotonicity had no effect on the linear staining patterns of occludin and Zo‐1, indicating no increase in paracellular permeability. Omission of calcium produced cholestasis characterized by a disruption of occludin, whereas the localization of Zo‐1, Bsep, and Mrp2 remained unaffected. It is concluded (1) that hyperosmolarity induces retrieval of Bsep from the canalicular membrane, which correlates to cholestasis. Hypoosmolarity leads to choleresis accompanied by a rapid recruitment of intracellular Bsep to the canalicular membrane. (2) Bsep‐ and Mrp2‐specific vesicles participate in the short‐term osmoregulation of canalicular secretion, however, a cause‐effect relationship between bile salt excretion and transporter localization remains to be established. (3) Ca2+‐depletion induces cholestasis by disruption of occludin‐determined tight junctional permeability, whereas internalization of canalicular transporters play a minor role.
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影响因子：
4
作者：
C. M. Itallie;James M. Anderson
通讯作者：
C. M. Itallie;James M. Anderson
DOI：
10.1152/ajprenal.1999.277.4.f524
发表时间：
1999-10
期刊：
American journal of physiology. Renal physiology
影响因子：
--
作者：
Jiuming Ye;T. Tsukamoto;A. Sun;S. Nigam
通讯作者：
Jiuming Ye;T. Tsukamoto;A. Sun;S. Nigam
影响因子：
4
作者：
Karin M. McCarthy;I. Skare;Michael C. Stankewich;M. Furuse;S. Tsukita;R. Rogers;R. Lynch;E. Schneeb
通讯作者：
Karin M. McCarthy;I. Skare;Michael C. Stankewich;M. Furuse;S. Tsukita;R. Rogers;R. Lynch;E. Schneeb
影响因子：
15.9
作者：
Trauner, M;Arrese, M;Karpen, SJ
通讯作者：
Karpen, SJ
细胞外 Ca2 在肝胆汁形成和牛磺胆酸盐转运中的作用。
DOI：
10.1152/ajpgi.1985.249.6.g711
发表时间：
1985
期刊：
The American journal of physiology
影响因子：
--
作者：
Anwer,MS;Clayton,LM
通讯作者：
Clayton,LM