Human UGT1A8 and UGT1A10 mRNA are expressed in primary human hepatocytes

Drug Metab Pharmacokinet. 2007 Jun;22(3):152-61. doi: 10.2133/dmpk.22.152.

Abstract

It is widely believed that the UGT1A isoforms, UGT1A8 and -1A10, are expressed exclusively in extrahepatic tissues. In this work, human primary hepatocytes from six donors were analyzed for UGT1A8 and -1A10 mRNA expression by semi-quantitative RT-PCR. New primers to amplify UGT1A8 mRNA were designed and found to differ from those previously published. We demonstrated that UGT1A8 and -1A10 mRNA are expressed in hepatocytes. Although basal UGT mRNA levels were detected in untreated hepatocytes, significant up-regulation of the levels of mRNA for these isoforms were seen after treatment with 3-methylcholanthrene (3-MC) and rifampicin (Rif). RT-PCR products for all UGTs were sequenced and unambiguously identified as matching the corresponding cDNA. The discovery of these isoforms in hepatocytes is a novel discovery and will stimulate studies on the potential role for these isoforms in hepatic detoxification.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • Cells, Cultured
  • Child, Preschool
  • Female
  • Gastrointestinal Tract / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects
  • Glucuronosyltransferase / genetics*
  • Hepatocytes / cytology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism*
  • Humans
  • Intestinal Mucosa / metabolism
  • Isoenzymes / genetics
  • Male
  • Methylcholanthrene / pharmacology
  • Middle Aged
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rifampin / pharmacology
  • Sequence Homology, Nucleic Acid
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • Isoenzymes
  • RNA, Messenger
  • Methylcholanthrene
  • bilirubin uridine-diphosphoglucuronosyl transferase 1A10
  • Glucuronosyltransferase
  • UDP-glucuronosyltransferase 1A9
  • UDP-glucuronosyltransferase, UGT1A8
  • Rifampin