Bile-salt hydrophobicity is a key factor regulating rat liver plasma-membrane communication: relation to bilayer structure, fluidity and transporter expression and function

Abstract

Bile-salt hydrophobicity regulates biliary phospholipid secretion and subselection. The aim of this study was to determine whether bile salts can influence liver plasma membrane phospholipids and fluidity in relation to the ATP-dependent transporter. Rats were depleted of bile salts by overnight biliary diversion and then sodium taurocholate was infused intravenously at a constant rate (200nmol/min per 100g of body weight), followed by infusion of bile salts with various hydrophobicities (taurochenodeoxycholate, tauroursodeoxycholate, tauro-β-muricholate, tauro-α-muricholate at 200nmol/min per 100g of body weight). The hydrophobicity of the infused bile salts correlated with that of biliary phospholipids, but was inversely related to that of the canalicular membrane bilayer. Canalicular membrane fluidity (estimated by 1,6-diphenyl-1,3,5-hexatriene fluorescence depolarization) and expression of multidrug-resistance proteins (Mrp2, Mrp3) and apical Na+-dependent bile-salt transporter (ASBT) were increased by hydrophilic bile salts, although there was no marked change in the expression of P-glycoprotein subfamilies (Mdr2). Bile-salt export pump (Bsep) expression was increased along with increasing bile-salt hydrophobicity. Bile salts modulate canalicular membrane phospholipids and membrane fluidity, as well as the ATP-dependent transporter expression and function, and these actions are associated with their hydrophobicity. The cytoprotective effect of hydrophilic bile salts seems to be associated with induction of Mrp2, Mrp3 and ASBT.

Bile acid toxicity structure–activity relationships: Correlations between cell viability and lipophilicity in a panel of new and known bile acids using an oesophageal cell line (HET-1A)

“…Introduction of 3a-azides (15, 26) (i.e., with retention of configuration) was accomplished by generating first the b-bromides (39,42). The b-azides (16,27) could be obtained by direct SN2 substitution on the a-mesylates (40,43). Similarly, the 7-b azido analog of UDCA (34) was generated by treating the appropriately protected CDCA-derived mesylate (45) with NaN 3 in DMPU followed by deprotection in aqueous base.…”

“…1). Notably, eight of these retained an ionizable side chain (7)(8)(9)(15)(16)(17)(18)(19). For comparison, seven DCA analogs were assembled along with LagoDCA (28) the epimeric 12-bOH compound (Fig.…”

“…7 Membrane effects are important in this context too. BAs can modify membrane fluidity and composition [15][16][17] as well as protein mobilization and activation 18 without directly affecting barrier function. 19 Some of these effects resemble those observed with non-BA hydrophobic solutes such as cholesterol myristate and detergents n-octylglycoside and Triton-X, at sub-lytic concentrations.…”

Supplementary dietary calcium stimulates faecal fat and bile acid excretion, but does not protect against obesity and insulin resistance in C57BL/6J mice

“…The unexpected up-regulation of bile acid transporters Slc10a2 and Ostb that we found in the present study can be explained by the relative increase of hydrophilic bile acids in the intestinal lumen on the HCa diet, as Ca predominantly precipitates hydrophobic bile acids (24) . Asamoto et al (25) previously found that hydrophilic bile acids are associated with an induction of bile acid transporters. The up-regulation of Slc10a2 and Ostb also implies that the Cainduced increase in faecal excretion of bile acids does not necessarily lead to a reduced enterohepatic circulation (26) and a consequent reduction in energy expenditure (13) .…”

Recent understanding of cholesterol gallstone pathogenesis: implication to non-surgical therapeutic strategy

“…2). Such a translocation of ABCB11 is associated with a proportion of net bile salt hydrophobicity [13]. In the long term, the enterohepatic circulation of bile salts is controlled by the regulated gene transcription of the liver X receptor alpha (LXRa) and the farnesoid X receptor (FXR) [14] (Fig.…”