Ursodeoxycholic acid stabilizes the bile salt export pump in the apical membrane in MDCK II cells.

[benign recurrent intrahepatic cholestasis]

Ursodeoxycholic acid (UDCA ) partly exerts choleretic effects by modifying the function of the bile salt export pump (Bsep , ABCB 11 ). UDCA induces insertion of Bsep into the canalicular membrane of hepatocytes ; however , underlying mechanisms remain unknown . We aimed to elucidate molecular mechanisms behind UDCA-induced Bsep activation .We established MDCK II cells stably expressing both Bsep and Na (+)-taurocholate cotransporting polypeptide , and investigated the effect of UDCA on activity and protein expression of Bsep using these cells . We performed inhibitor study to know the molecules involved in UDCA-induced Bsep activation , and also tested the influence of UDCA on Bsep having a disease-associated mutation .UDCA activated Bsep in a dose-dependent manner . UDCA did not affect Bsep protein expression in whole cell lysates but increased its apical surface expression by extending the half -life from 2 .4 to 5 .0 Â h . This effect was specific to Bsep because UDCA did not affect other apical and basolateral proteins , and was independent of protein kinase A , adenylate cyclase , p 38 (MAPK ), phosphatidylinositide 3 -kinase , Ca (2 +), and microtubules . NorUDCA activated Bsep similar to UDCA ; however , cholic acid , taurocholic acid , and tauroUDCA had no effect . UDCA significantly increased the activity of Bsep with a benign recurrent intrahepatic cholestasis 2 mutation (A 570 T ) but did not affect Bsep with a progressive familial intrahepatic cholestasis 2 mutation (G 982 R or D 482 G ).We demonstrated that UDCA stabilizes Bsep protein in the apical membrane and increases its activity in MDCK II cells , presumably by retarding the endocytotic process .

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Diseases presenting "partly exerts" symptom

benign recurrent intrahepatic cholestasis

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