Journal of Lipid Research, Vol 31, 1063-1071, Copyright © 1990 by Lipid Research, Inc.
Bile salts in submicellar concentrations promote bidirectional cholesterol transfer (exchange) as a function of their hydrophobicity
ZR Vlahcevic, EC Gurley, DM Heuman and PB Hylemon
Department of Medicine, (Division of Gastroenterology), Medical College of Virginia, Richmond 23298.
Cholesterol, despite its poor solubility in aqueous solutions, exchanges
efficiently between membranes. Movement of cholesterol between different
subcellular membranes in the hepatocyte is necessary for assembly of
lipoproteins, biliary cholesterol secretion, and bile acid synthesis.
Factors which initiate and facilitate transfer of cholesterol between
different membranes in the hepatocyte are incompletely understood. It is
known that cholesterol secretion into the bile is linked to bile salt
secretion. In the present study, we investigated the effects of bile salts
of different physicochemical properties at submicellar concentrations (150-
600 microM) on the transfer of [14C]cholesterol from hepatocytes, or crude
hepatocellular membranes (donors), to rat high density lipoproteins
(acceptor). Bile salts included taurine conjugates of ursodeoxycholic acid
(TUDCA), hyodeoxycholic acid (THDCA), cholic acid (TCA), chenodeoxycholic
acid (TCDCA), and deoxycholic acid (TDCA). High density lipoprotein (HDL)
was separated from hepatocellular membranes and the transfer of
[14C]cholesterol from the membranes to HDL was quantitatively determined.
In the absence of HDL, [14C]cholesterol remained confined to the membrane
fraction. Following addition of HDL, [4-14C]cholesterol in the HDL fraction
increased linearly over time. Addition of hydrophilic bile salts (TUDCA and
THDCA) increased transfer of [4- 14C]cholesterol to HDL only minimally. By
contrast, more hydrophobic bile salts stimulated transfer of labeled
cholesterol to HDL, and their potency increased in order of increasing
hydrophobicity (TCA less than TCDCA less than TDCA). Both for single bile
salts and mixtures of bile salts at a total bile salt concentration of 0.30
mM, the rate of cholesterol transfer exhibited a strong linear correlation
with a bile salt monomeric hydrophobicity index (r = 0.95; P less than
0.001).(ABSTRACT TRUNCATED AT 250 WORDS)