Feedback inhibition of bile acid synthesis in cultured pig hepatocytes

article



Kwekkeboom, J.

Voorthuizen, E.M. van

Princen, H.M.G.

Kempen, H.J.
Bile acid synthesis by cultured pig hepatocytes, as measured by conversion of [14C]cholesterol to bile acids, increased during the second and third day of culture. This rise was inhibited after addition of various conjugated and unconjugated bile acids in a concentration of 100 μM. It could be completely prevented by cycloheximide, indicating that de novo protein synthesis is required for the increase in bile acid formation. No effect of exogenous bile salts on LDH release to the medium or on cellular ATP content was observed, demonstrating that hepatocyte viability was not affected. During the period in which bile acid synthesis was inhibited, pig hepatocytes were able to accumulate taurocholic acid (100 μM) up to 7-18 nmol per mg cell protein (decreasing during culture time). It is concluded that feedback regulation of bile acid synthesis is exerted by direct action of bile acids on the hepatocyte.
Chemicals/CAS: Bile Acids and Salts; Cholesterol, 57-88-5; Cycloheximide, 66-81-9; Taurocholic Acid, 81-24-3
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radioisotopeanimal cellbile acid synthesiscell cultureliver cellmetabolic regulationnegative feedbacknonhumanpriority journalAnimalBile Acids and SaltsCell SurvivalCells, CulturedCholesterolCycloheximideFemaleLiverSupport, Non-U.S. Gov'tSwineTaurocholic Acid
TNO Identifier
230583
Repository link
https://resolver.tno.nl/uuid:9ddc43de-6266-48ce-b53f-6f807c50ab95
ISSN
0006291X
Source
Biochemical and Biophysical Research Communications, 155(2), pp. 850-856.
Pages
850-856
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