Differential lobular induction in rat liver of glutathione S-transferase A1/A2 by phenobarbital

Niazy Selim, Gene D. Branum, Xia Liu, Richard Whalen, Thomas D. Boyer

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Phenobarbital and other xenobiotics induce drug-metabolizing enzymes, including glutathione S-transferase A1/A2 (rGSTA1/A2). We examined the mechanism of induction of rGSTA1/A2 in rat livers after phenobarbital treatment. The induction of rGSTA1/A2 was not uniform across the hepatic lobule; steady-state transcript levels were threefold higher in perivenous hepatocytes relative to periportal hepatocytes when examined by in situ hybridization 12 h after a single dose of phenobarbital. Administration of a second dose of phenobarbital 12 or 24 h after the first dose did not equalize the induction of rGSTA1/A2 across the lobule. The transcriptional activity of the rGSTA1/A2 gene was increased 3.5- to 5.5-fold in whole liver by phenobarbital, but activities were the same in enriched periportal and perivenous subpopulations of hepatocytes from phenobarbital-treated animals. The half-life of rGSTA1/A2 mRNA in control animals was 3.6 h, whereas it was 10.2 h in phenobarbital-treated animals. We conclude that phenobarbital induces rGSTA1/A2 expression by increasing transcriptional activity across the lobule but induction of rGSTA1/A2 is greater in perivenous hepatocytes due to localized stabilization of mRNA transcripts.

Original languageEnglish (US)
Pages (from-to)G542-G550
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume278
Issue number4 41-4
DOIs
StatePublished - Apr 2000

Keywords

  • Detoxication
  • Enzyme
  • Half-life
  • Regulation
  • mRNA

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Differential lobular induction in rat liver of glutathione S-transferase A1/A2 by phenobarbital'. Together they form a unique fingerprint.

  • Cite this