Hepatocelluar cytoprotection by hydrophilic bile salts is through enhancing canalicular membrane fluidity and packing density

2000 ◽  
Vol 118 (4) ◽  
pp. A1422
Author(s):  
Yasumasa Asamoto ◽  
Susumu Tazuma ◽  
Hidenori Ochi ◽  
Tsuyoshi Kajihara ◽  
Hideyuki Hyougo ◽  
...  
Keyword(s):  
Membrane Fluidity ◽  
Packing Density ◽  
Bile Salts ◽  
Canalicular Membrane

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

2001 ◽  
Vol 359 (3) ◽  
pp. 605-610 ◽  
Author(s):  
Yasumasa ASAMOTO ◽  
Susumu TAZUMA ◽  
Hidenori OCHI ◽  
Kazuaki CHAYAMA ◽  
Hiroshi SUZUKI
Keyword(s):  
Body Weight ◽  
Plasma Membrane ◽  
Bile Salt ◽  
Membrane Fluidity ◽  
Bile Salts ◽  
Membrane Phospholipids ◽  
Canalicular Membrane ◽  
Liver Plasma Membrane ◽  
And Function ◽  
Transporter Expression

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.

Hydrophilic bile salts cytoprotectively function against cyclosporine A caused cholestasis through enhacing canalicular membrane fluidity and transporter activity

2001 ◽  
Vol 120 (5) ◽  
pp. A549
Author(s):  
Kazuhiko Tsuboi ◽  
Susumu Tazuma ◽  
Hidenori Ochi ◽  
Tomoji Nishioka ◽  
Shigeyuki Yasumba ◽  
...  
Keyword(s):  
Membrane Fluidity ◽  
Cyclosporine A ◽  
Bile Salts ◽  
Canalicular Membrane

Hepatic bile flow

1984 ◽  
Vol 64 (4) ◽  
pp. 1055-1102 ◽  
Author(s):  
R. C. Strange
Keyword(s):  
Bile Salt ◽  
Bile Salts ◽  
Basolateral Membrane ◽  
Membrane Vesicles ◽  
Critical Micellar Concentration ◽  
Canalicular Membrane ◽  
Receptor Proteins ◽  
Subcellular Organelles ◽  
Golgi Bodies ◽  
Initial Event

The hepatocyte is a polar cell that can remove a variety of molecules from blood and excrete them into bile. This review is primarily concerned with the mechanism of transport of the principal anions--the bile salts--across the sinusoidal membrane, their passage through the cell, and excretion across the canalicular membrane. Clearly much of this process is poorly understood, but the study of the membrane stages should be facilitated by the ability to prepare purified sinusoidal and canalicular membrane vesicles. For example, the relative importance of albumin-binding sites as well as the putative bile salt receptor proteins can be better assessed. It seems likely that although the interaction of bile salts with receptor proteins is important, it is an initial event that puts the bile salt in the correct place for uptake to occur. The driving force for uptake is the Na+ gradient created across the basolateral membrane by the activity of the Na+-K+-ATPase. Within the cell, various modes of transport have been suggested. Several authors emphasize the importance of protein binding of bile salts, either because of their presumed ability to maintain the concentration of these anions in the hepatocyte below their critical micellar concentration or because of their putative role in transport. It is important to understand these aspects of the role of cytosolic proteins for several reasons. Knowledge of the true concentration of free bile salt within the cell should allow estimation of whether the electrochemical gradient is sufficient for bile salts to accumulate in bile without the need for active transport of molecules from the cell into the canaliculus. The compartmental model described by Strange et al. (153) offers one theoretical way of determining the concentration of free bile salt, although the problems inherent in studying amphipath binding to the membranes of subcellular organelles (31) require that the model be reevaluated by the hygroscopic-desorption method. The second role suggested for the cytosolic bile salt-binding proteins is as transport proteins. As discussed in section VI, I think it is unlikely that the proteins identified so far act in this way, and it is more likely that movement occurs by diffusion in free solution. It is also important to determine the possible involvement of subcellular organelles such as Golgi bodies. Little is known of their role in the transport of bile salts or indeed where bile salt micelles are formed.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Cyclosporin A reduces canalicular membrane fluidity and regulates transporter function in rats

2001 ◽  
Vol 354 (3) ◽  
pp. 591 ◽  
Author(s):  
Shigeyuki YASUMIBA ◽  
Susumu TAZUMA ◽  
Hidenori OCHI ◽  
Kazuaki CHAYAMA ◽  
Goro KAJIYAMA
Keyword(s):  
Cyclosporin A ◽  
Membrane Fluidity ◽  
Canalicular Membrane

scholarly journals The effects of colchicine on secretion into bile of bile salts, phospholipids, cholesterol and plasma membrane enzymes: bile salts are secreted unaccompanied by phospholipids and cholesterol

1984 ◽  
Vol 220 (3) ◽  
pp. 723-731 ◽  
Author(s):  
S G Barnwell ◽  
P J Lowe ◽  
R Coleman
Keyword(s):  
Plasma Membrane ◽  
Protective Effect ◽  
Bile Salt ◽  
Aspartate Aminotransferase ◽  
Bile Salts ◽  
Membrane Damage ◽  
Aminotransferase Activity ◽  
Canalicular Membrane ◽  
Membrane Enzymes ◽  
Taurocholate Transport

Colchicine, a drug which interferes with microtubular function, has no effect on the secretion of taurodehydrocholate into bile; it is therefore suggested that bile salts are unlikely to be packaged in vesicles during cellular transit from sinusoidal to canalicular membranes. Colchicine greatly reduces the secretion of phospholipid and cholesterol into bile; it is suggested that this is due to an interruption in the supply of vesicles bringing lipids to repair the canalicular membrane during bile salt output. In the absence of the protective effect of a continuous supply of repair vesicles, micelleforming bile salts damage the canalicular membrane; the increased concentration of plasma membrane enzymes in bile and the increased aspartate aminotransferase activity in plasma and bile are evidence of this damage. Damage to the canalicular membrane may also be an explanation for the reduction in taurocholate transport and the taurocholate-induced cholestasis which are seen with colchicine-treated livers. Such membrane damage is not observed in colchicine-treated livers during the secretion of the non-micelle forming bile salt, taurodehydrocholate.

Bile salt excretion in skate liver is mediated by a functional analog of Bsep/Spgp, the bile salt export pump

2000 ◽  
Vol 278 (1) ◽  
pp. G57-G63 ◽  
Author(s):  
Nazzareno Ballatori ◽  
James F. Rebbeor ◽  
Gregory C. Connolly ◽  
David J. Seward ◽  
Benjamin E. Lenth ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Bile Salt ◽  
Rat Liver ◽  
Bile Salts ◽  
Plasma Membranes ◽  
Functional Characterization ◽  
Salt Transport ◽  
Positive Staining ◽  
Transport Activity ◽  
Canalicular Membrane

Biliary secretion of bile salts in mammals is mediated in part by the liver-specific ATP-dependent canalicular membrane protein Bsep/Spgp, a member of the ATP-binding cassette superfamily. We examined whether a similar transport activity exists in the liver of the evolutionarily primitive marine fish Raja erinacea, the little skate, which synthesizes mainly sulfated bile alcohols rather than bile salts. Western blot analysis of skate liver plasma membranes using antiserum raised against rat liver Bsep/Spgp demonstrated a dominant protein band with an apparent molecular mass of 210 kDa, a size larger than that in rat liver canalicular membranes, ∼160 kDa. Immunofluorescent localization with anti-Bsep/Spgp in isolated, polarized skate hepatocyte clusters revealed positive staining of the bile canaliculi, consistent with its selective apical localization in mammalian liver. Functional characterization of putative ATP-dependent canalicular bile salt transport activity was assessed in skate liver plasma membrane vesicles, with [3H]taurocholate as the substrate. [3H]taurocholate uptake into the vesicles was mediated by ATP-dependent and -independent mechanisms. The ATP-dependent component was saturable, with a Michaelis-Menten constant ( K m) for taurocholate of 40 ± 7 μM and a K m for ATP of 0.6 ± 0.1 mM, and was competitively inhibited by scymnol sulfate (inhibition constant of 23 μM), the major bile salt in skate bile. ATP-dependent uptake of taurocholate into vesicles was inhibited by known substrates and inhibitors of Bsep/Spgp, including other bile salts and bile salt derivatives, but not by inhibitors of the multidrug resistance protein-1 or the canalicular multidrug resistance-associated protein, indicating a distinct transport mechanism. These findings provide functional and structural evidence for a Bsep/Spgp-like protein in the canalicular membrane of the skate liver. This transporter is expressed early in vertebrate evolution and transports both bile salts and bile alcohols.

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