Regulation of sulfotransferase enzymes by prototypical microsomal enzyme inducers in mice

Yazen Alnouti, Curtis D. Klaassen

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

In the present study, the regulation of the mRNA of 11 sulfotransferases (Sults) and two 3′-phosphoadenosine 5′-phosphosulfate synthase (PAPSs) isozymes by 15 microsomal enzyme inducers (MEI) in livers of male mice and five MEIs in livers of female mice was examined. These MEIs represent the transcriptionally mediated pathways: aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), constitutive androstane receptor (CAR), peroxisomal proliferator-activated receptor α (PPARα), and NF-E2-related factor 2 (Nrf2). AhR ligands suppress the expression of Sults, especially the Sult1 isoenzymes in female mice. CAR activators up-regulate several Sults and PAPSs2 in female but not in male mice. PXR ligands cause marked induction of Sult1e1 in male, Sult2a1/2a2 in female, and PAPSs2 in both male and female mice. PPARα ligands do not have a marked effect on Sult expression in males, but they tend to suppress the expression of several Sult isoforms in female mice. Nrf2 activators appear to induce the mRNA expression of Sults in male and have mixed effects in female mice. In silico analysis indicated the presence of putative binding sites for all five transcription factors in the promoter region of many Sult and PAPSs isoforms. In conclusion, induction of Sults by typical MEIs is not as marked as the induction of P450 enzymes in mice. In addition to gender differences in basal expression of Sults, there is also a marked gender difference in the inducibility of various Sult isoenzymes in mice by MEIs.

Original languageEnglish (US)
Pages (from-to)612-621
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume324
Issue number2
DOIs
StatePublished - Feb 1 2008

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Sulfotransferases
Enzymes
NF-E2-Related Factor 2
Isoenzymes
Aryl Hydrocarbon Receptors
Ligands
Protein Isoforms
Phosphoadenosine Phosphosulfate
Messenger RNA
Liver
Genetic Promoter Regions
Computer Simulation
Cytochrome P-450 Enzyme System
Transcription Factors
Up-Regulation
Binding Sites

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Regulation of sulfotransferase enzymes by prototypical microsomal enzyme inducers in mice. / Alnouti, Yazen; Klaassen, Curtis D.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 324, No. 2, 01.02.2008, p. 612-621.

Research output: Contribution to journalArticle

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