Membrane cholesterol content of cholesterol/phospholipid vesicles determines the susceptibility to both damage and protection by bile salts: implications for bile physiology.
OBJECTIVE
To investigate the effect of membrane lipid composition on the susceptibility to bile salt damage and protection.


METHODS
Artificial model cholesterol/phospholipid (c/p) membranes (vesicles) with a varying cholesterol (0-15 mM) and phospholipid content (3-30 mM), and with a c/p ratio ranging up to 1.70, were prepared by sonication. We examined the effect of incubation with increasing concentrations of either tauroursodeoxycholate (TUDC), taurocholate (TC) or taurodeoxycholate (TDC) alone, or with proportionally varying mixtures of TUDC and TDC.


METHODS
Vesicle integrity was assessed by the change in optical absorbance at 340 nm.


RESULTS
Absorption of the bile salt-vesicle mixture decreased, with increasing bile salt concentration and hydrophobicity: TUDC less than TC less than TDC. Moreover, bile salt-induced damage also depended on membrane composition: vesicles containing more than 5 mM cholesterol and with a c/p ratio greater than 0.8 were less likely to be solubilized by 30 mM bile salt. Similarly, only in cholesterol-rich vesicles (c/p > 0.5) was a protective effect of TUDC against membrane disruption by TDC revealed upon incubation with various TUDC/TDC mixtures.


CONCLUSIONS
Apart from the bile salt concentration and hydrophobicity, the cholesterol content of vesicles is pivotal, both in the bile salt-induced solubilization of cholesterol/phospholipid vesicles and in the potency of TUDC to prevent this.
van de Heijning
B J
BJ
Department of Gastroenterology, University Hospital Utrecht, The Netherlands.
van den Broek
A M
AM
van Berge-Henegouwen
G P
GP
D001646:Bile / Q000502:physiology*; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002784:Cholesterol / Q000032:analysis* / Q000378:metabolism; D008567:Membranes, Artificial; D008954:Models, Biological; D010743:Phospholipids / Q000032:analysis* / Q000378:metabolism; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology; D013656:Taurocholic Acid / Q000494:pharmacology; D013657:Taurodeoxycholic Acid / Q000494:pharmacology; D014461:Ultracentrifugation
D001647:Bile Acids and Salts; D008567:Membranes, Artificial; D010743:Phospholipids; D013655:Taurochenodeoxycholic Acid; D013657:Taurodeoxycholic Acid; D013656:Taurocholic Acid; C031655:ursodoxicoltaurine; D002784:Cholesterol