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Bilirubin and bile acids may modulate their own metabolism via regulating uridine diphosphate‐glucuronosyltransferase expression in the rat
Author(s) -
Li Yan Q,
Prentice David A,
Howard Monique L,
Mashford Maurice L,
Desmond Paul V
Publication year - 2000
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1046/j.1440-1746.2000.02223.x
Subject(s) - glucuronidation , bilirubin , uridine diphosphate , chenodeoxycholic acid , glucuronosyltransferase , deoxycholic acid , cholic acid , lithocholic acid , bile acid , biochemistry , metabolism , uridine , cyp8b1 , chemistry , medicine , endocrinology , enzyme , biology , microsome , rna , gene
Background and Aims: Uridine diphosphate (UDP)‐glucuronosyltransferase (UGT) is a critical enzyme in the elimination of bilirubin and it also plays a role in the metabolism of bile acids. The aim of this study was to determine whether bilirubin and bile acids could modulate their own metabolism by regulating UGT levels in cultured rat hepatocytes.Methods and Results: Incubation of hepatocytes with bilirubin (48 μmol/L) for 24 h significantly increased the mRNA expression of UGT1A1 and UGT1A5, two UGT isoforms responsible for the conjugation of bilirubin. The induction of UGT1A1 and UGT1A5 by bilirubin was concentration and time dependent. Treatment with chenodeoxycholic acid, cholic acid, deoxycholic acid, hyodeoxycholic acid and lithocholic acid at a concentration of 100 μmol/L for 48 h significantly enhanced the mRNA expression of UGT2B1, a UGT isoform responsible for the glucuronidation of bile acids. The UGT2B3 mRNA level was also increased by hyodeoxycholic acid. The regulation of UGT2B1 mRNA by chenodeoxycholic acid and hyodeoxycholic acid was dose and time dependent.Conclusion: Our results suggest that bilirubin and bile acids can induce UGT expression and as a result, these compounds may modulate their own metabolism. Such regulation could play a compensatory role in the pathological increased concentrations of these compounds in some hepatobiliary diseases.