HepG2. A human hepatoblastoma cell line exhibiting defects in bile acid synthesis and conjugation.
We used capillary gas chromatography/mass spectrometry to demonstrate that a cell line derived from a well differentiated human hepatoblastoma, HepG2, synthesized and secreted the following bile acids (ng/10(7) cells/h): chenodeoxycholic acid (131.4), cholic acid (3.3), 3 alpha, 7 alpha-dihydroxy-5 beta-cholestan-26-oic acid (DHCA; 4.5), and 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestan-26-oic acid (THCA; 32.0). Deuterium from [7 beta-2H]7 alpha-hydroxycholesterol, which was added to the media, was incorporated into newly synthesized chenodeoxycholic acid, DHCA, and THCA, but not into cholic acid. Since THCA is a known precursor of cholic acid, these data suggest that HepG2 is specifically deficient in the side chain cleavage that transforms THCA into cholic acid. Greater than 90% of the bile acids synthesized and secreted by HepG2 were unconjugated. Conjugation could not be stimulated by the addition of glycine or taurine to the media. Approximately 30% of newly synthesized DHCA and THCA were sulfated. Chenodeoxycholic acid and cholic acid were not appreciably sulfated. In summary, cultured HepG2 cells synthesize bile acid, but in a pattern distinct from that of adult human liver. This cell line may be a model for studying pathways of human bile acid synthesis, conjugation, and sulfation.
D001647:Bile Acids and Salts / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D002635:Chenodeoxycholic Acid / Q000032:analysis; D002777:Cholestanols / Q000032:analysis; D019826:Cholic Acid; D002793:Cholic Acids / Q000032:analysis; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology
C000986:3,7-dihydroxycholestan-26-oic acid; D001647:Bile Acids and Salts; D002777:Cholestanols; D002793:Cholic Acids; D002635:Chenodeoxycholic Acid; C022069:3,7,12-trihydroxycholestan-26-oic acid; D019826:Cholic Acid