Determinants of Biliary Lipid Excretion

Author(s):  
H. O. Wheeler ◽  
R. J. May ◽  
P. M. Loeb
2004 ◽  
Vol 286 (5) ◽  
pp. G762-G768 ◽  
Author(s):  
Ronald P. J. Oude Elferink ◽  
Roelof Ottenhoff ◽  
Gert Fricker ◽  
David J. Seward ◽  
Nazzareno Ballatori ◽  
...  

The ABC transporters bile salt export pump (BSEP; encoded by the ABCB11 gene), MDR3 P-glycoprotein ( ABCB4), and sterolin 1 and 2 ( ABCG5 and ABCG8) are crucial for the excretion of bile salt, phospholipid, and cholesterol, respectively, into the bile of mammals. The current paradigm is that phospholipid excretion mainly serves to protect membranes of the biliary tree against bile salt micelles. Bile salt composition and cytotoxicity, however, differ greatly between species. We investigated whether biliary phospholipid and cholesterol excretion occurs in a primitive species, the little skate, which almost exclusively excretes the sulphated bile alcohol scymnolsulphate. We observed no phospholipid and very little cholesterol excretion into bile of these animals. Conversely, when scymnolsulphate was added to the perfusate of isolated mouse liver perfusions, it was very well capable of driving biliary phospholipid and cholesterol excretion. Furthermore, in an erythrocyte cytolysis assay, scymnolsulphate was found to be at least as cytotoxic as taurocholate. These results demonstrate that the little skate does not have a system for the excretion of phospholipid and cholesterol and that both the MDR3 and the two half-transporter genes, ABCG5 and ABCG8, have evolved relatively late in evolution to mediate biliary lipid excretion. Little skate plasma membranes may be protected against bile salt micelles mainly by their high sphingomyelin content.


1991 ◽  
Vol 260 (1) ◽  
pp. G119-G132 ◽  
Author(s):  
J. M. Crawford ◽  
D. W. Vinter ◽  
J. L. Gollan

The mechanisms and pathways involved in hepatocellular transport of lipid destined for biliary excretion remain poorly understood. Using fluorescence microscopy of rat hepatocyte couplets in primary culture, we examined the effects of taurocholate (TC) on the intracellular distribution of 6-N-[7-nitrobenz-2-oxa-1,3-diazol- 4-yl]aminocaproyl-sphingosine (C6-NBD-ceramide), a lipid that accumulates in the Golgi apparatus. Microscopic findings were quantified with morphometric and digital image analysis and were correlated with the metabolism of C6-NBD-ceramide in isolated hepatocyte suspensions and the biliary excretion of fluorescent lipid in the isolated perfused liver. After plasma membrane uptake of C6-NBD-ceramide from albumin at 0 degrees C, the lipid was rapidly internalized at 37 degrees C but exhibited only a modest concentration of fluorescence in intracellular organelles. With 17 microM TC in the medium, there was enhanced localization of fluorescence to organelles and significant recruitment of fluorescent lipid to the pericanalicular region of the couples within 30 min. C6-NBD-ceramide was partially metabolized to C6-NBD-sphingomyelin and -glucosylceramide, indicative of transit through the Golgi apparatus. The generation of C6-NBD-sphingomyelin was significantly increased by TC. After a similar loading protocol in the perfused liver, there was little biliary excretion of fluorescent lipid at 37 degrees C under control conditions. However, infusion of TC markedly enhanced the biliary output of fluorescent lipid over the first 30 min, primarily as C6-NBD-sphingomyelin and -glucosylceramide. We conclude that TC modulates the distribution of C6-NBD-ceramide in hepatocytes by inducing translocation of lipid to a pericanalicular location, most likely the Golgi apparatus, before excretion of its metabolites in bile. Our findings support the concept that bile salt-induced biliary lipid excretion is facilitated by the interaction of bile salts with lipids at the level of intracellular organelles.


1968 ◽  
Vol 13 (12) ◽  
pp. 1077-1080 ◽  
Author(s):  
Leon Swell ◽  
C. C. Bell

2002 ◽  
Vol 34 (4) ◽  
pp. 291-299 ◽  
Author(s):  
A. Mizuta ◽  
K. Chijiiwa ◽  
S. Saiki ◽  
S. Kuroki ◽  
K. Nakamura ◽  
...  

1981 ◽  
Vol 81 (4) ◽  
pp. 817
Author(s):  
E.A. Shaffer ◽  
R.M. Preshaw

1978 ◽  
Vol 23 (1) ◽  
pp. 85-88 ◽  
Author(s):  
Charles I. Wagner ◽  
Bruce W. Trotman ◽  
Roger D. Soloway

Kanzo ◽  
1993 ◽  
Vol 34 (8) ◽  
pp. 611-620
Author(s):  
Asamitsu HIRANO ◽  
Makoto HOSHINO ◽  
Tomihiro HAYAKAWA

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