Expression of Sterol 12α-Hydroxylase Alters Bile Acid Pool Composition in Primary Rat Hepatocytes and In Vivo

Background & Aims: The rate of 12α-hydroxylation of bile acid intermediates is believed to determine the ratio of cholic acid (CA) to chenodeoxycholic acid (CDCA) biosynthesis and the overall hydrophobicity of the bile acid pool. The aim of this study was to determine the effects of the level of...

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Veröffentlicht in:	Gastroenterology (New York, N.Y. 1943) N.Y. 1943), 2001-06, Vol.120 (7), p.1801-1809
Hauptverfasser:	Pandak, William M., Bohdan, Patricia, Franklund, Clifton, Mallonee, Darrell H., Eggertsen, Gösta, Björkhem, Ingemar, Gil, Gregorio, Vlahcevic, Z. Reno, Hylemon, Phillip B.
Format:	Artikel
Sprache:	eng
Schlagworte:	Biological and medical sciences Fundamental and applied biological sciences. Psychology Liver. Bile. Biliary tracts Vertebrates: digestive system
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Zusammenfassung:	Background & Aims: The rate of 12α-hydroxylation of bile acid intermediates is believed to determine the ratio of cholic acid (CA) to chenodeoxycholic acid (CDCA) biosynthesis and the overall hydrophobicity of the bile acid pool. The aim of this study was to determine the effects of the level of expression of sterol 12α-hydroxy-lase (CYP8b1) and cholesterol 7α-hydroxylase (CYP7a1) on rates of CA biosynthesis and bile acid pool composition. Methods: Expression of CYP8b1 and CYP7a1 was accomplished through infection of primary rat hepatocytes (PRH) or intact male SD rats with replicationdefective recombinant adenoviruses encoding either CYP8b1 or CYP7a1. Results: Increased expression of CYP7a1 over basal levels in PRH dramatically increased bile acid biosynthesis (586% ± 82%, P
ISSN:	0016-5085 1528-0012
DOI:	10.1053/gast.2001.24833