Mitogen-activated protein kinases mediate the stimulation of bile acid secretion by tauroursodeoxycholate in rat liver

Schliess, Freimut; Kurz, AK; Dahl, Stephan Vom; Häussinger, Dieter

doi:10.1053/gast.1997.v113.pm9322526

Cited by 116 publications

(126 citation statements)

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“…As part of its choleretic effect, TUDC stimulates insertion of the canalicular transporter Bsep and Mrp2 by activation of Erks and p38 MAPK (25,50) and counteracts internalization in taurolithocholate-induced cholestasis (29). In this study, the choleretic effect of TUDC may reside in the prevention of hyperosmotic Fyn activation and cAMP formation.…”

Section: Discussionmentioning

confidence: 70%

Regulation of Plasma Membrane Localization of the Na+-taurocholate cotransporting polypeptide (Ntcp) by Hyperosmolarity and Tauroursodeoxycholate

et al. 2015

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Background:Little is known about the effect of hyperosmotic hepatocyte shrinkage on Na ϩ -taurocholate cotransporting polypeptide (Ntcp) regulation. Results: Hyperosmolarity induces a Fyn-dependent retrieval of Ntcp, which is reversed by tauroursodeoxycholate via a ␤ 1 -integrin-mediated formation of cAMP. Conclusion: Fyn and ␤ 1 -integrins are novel regulators of Ntcp localization. Significance: The study provides new insights into the regulation of bile salt transport.

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Section: Discussionmentioning

confidence: 70%

Regulation of Plasma Membrane Localization of the Na+-taurocholate cotransporting polypeptide (Ntcp) by Hyperosmolarity and Tauroursodeoxycholate

et al. 2015

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“…25,48,49 Upstream signaling involves integrin sensing, focal adhesion kinases (FAK), and Src kinase activation. 50 In contrast, in isolated rat hepatocytes, inhibition of MEK1, an upstream effector of Erk1/2, failed to affect cell swelling-induced translocation of Ntcp to the plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

“…An effect on TC* recovery in the effluent or secretion into bile was not observed. 25,48,49 Furthermore, cell swelling causes Ntcp exocytosis by way of PI3K. 20 cAMP stimulates protein phosphatase 2B-mediated dephosphorylation of NTCP and leads to an increased retention of Ntcp at the plasma membrane.…”

Section: Tcdc Induces Redistribution Of Ntcp In Perfusedmentioning

confidence: 99%

Short-term feedback regulation of bile salt uptake by bile salts in rodent liver

et al. 2012

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The sodium taurocholate cotransporting polypeptide (Ntcp) is the major bile salt uptake transporter at the sinusoidal membrane of hepatocytes. Short-term feedback regulation of Ntcp by primary bile salts has not yet been investigated in vivo. Subcellular localization of Ntcp was analyzed in Ntcp-transfected HepG2-cells by flow cytometry and in immunofluorescence images from tissue sections by a new automated image analysis method. Net bile salt uptake was investigated in perfused rat liver by a pulse chase technique. In Flag-Ntcp-EGFP (enhanced green fluorescent protein) expressing HepG2-cells, taurochenodeoxycholate (TCDC), but not taurocholate (TC), induced endocytosis of Ntcp. TCDC, but not TC, caused significant internalization of Ntcp in perfused rat livers, as shown by an increase in intracellular Ntcp immunoreactivity, whereas Bsep distribution remained unchanged. These results correlate with functional studies. Rat livers were continuously perfused with 100 mu mol/L of TC. 25 mu mol/L of TCDC, taurodeoxycholate (TDC), tauroursodeoxycholate (TUDC), or TC were added for 30 minutes, washed out, followed by a pulse of (3)[H]-TC. TCDC, but not TDC, TUDC, or TC significantly increased the amount of (3)[H]-TC in the effluent, indicating a reduced sinusoidal net TC uptake. This effect was sensitive to chelerythrine (protein kinase C inhibitor) and cypermethrin (protein phosphatase 2B inhibitor). Phosphoinositide 3-kinase (PI3K) inhibitors had an additive effect, whereas Erk1/2 (extracellular signal activated kinase 1/2), p38MAPK, protein phosphatase 1/2A (PP1/2A), and reactive oxygen species (ROS) were not involved. Conclusion: TCDC regulates bile salt transport at the sinusoidal membrane by protein kinase C-and protein phosphatase 2B-mediated retrieval of Ntcp from the plasma membrane. During increased portal bile salt load this mechanism may adjust bile salt uptake along the acinus and protect periportal hepatocytes from harmful bile salt concentrations

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“…Based on all these observations, it has been postulated that two separate intracellular pools exist within hepatocytes, from which Bsep can be recruited and inserted into the canalicular plasma membrane under the conditions of increased bile flow rates [47]. In addition to these pathways, the mitogenactivated kinase cascades are also involved in the posttranscriptional regulation of Bsep expression: Induction of choleresis by tauroursodeoxycholic acid or alteration of bile flow by anisosomolarity leads to canalicular insertion/ retrieval of Bsep, a process that is critically dependent on mitogen-activated kinases [83]. In addition, studies in polarized cell lines expressing Bsep revealed that HAX-1 and myosin II regulatory light chain are required for the trafficking of Bsep to the apical membrane as well as in the regulation of its abundance in the apical plasma membrane of MDCK cells [12,73].…”

Section: Ontogenesis and Regulationmentioning

confidence: 99%

The bile salt export pump

Stieger

Meier

2006

Pflugers Arch - Eur J Physiol

207

137

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Mitogen-activated protein kinases mediate the stimulation of bile acid secretion by tauroursodeoxycholate in rat liver

Cited by 116 publications

References 4 publications

Regulation of Plasma Membrane Localization of the Na+-taurocholate cotransporting polypeptide (Ntcp) by Hyperosmolarity and Tauroursodeoxycholate

Regulation of Plasma Membrane Localization of the Na+-taurocholate cotransporting polypeptide (Ntcp) by Hyperosmolarity and Tauroursodeoxycholate

Short-term feedback regulation of bile salt uptake by bile salts in rodent liver

The bile salt export pump

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