ToxSci Advance Access published online on August 22, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn179
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Induction of Hepatic Glutathione S-Transferases in Male Mice By Prototypes of Various Classes of Microsomal Enzyme Inducers1
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA 2 Current address: Food and Drug Administration, Center for Food Safety and Applied Nutrition, OFAS/DBGNR, College Park, MD 20740
3 To whom requests for reprints should be addressed: Department of Pharmacology, Toxicicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160-7417, USA., Phone: (913) 588-7714; Fax: (913) 588-7501; E-mail: cklaasse{at}kumc.edu
Received June 25, 2008; revision received August 18, 2008; accepted August 19, 2008
 |
Abstract |
|---|
The underlying need for glutathione S-transferase (Gst) induction is thought to be an adaptive response to chemical stress within the cell. Classical microsomal enzyme inducers (MEIs) increase the expression of biotransformation enzymes (phase-I and -II) and transporters through transcription factors, such as the aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferators-activated receptor alpha (PPAR
), and NF-E2 related factor 2 (Nrf2). The effects of MEIs on the induction of hepatic glutathione S-transferases in mice have not been comprehensively characterized. The purpose of this study was to determine the effects of 15 MEIs on the mRNA expression of 19 mouse Gsts. Male C57BL/6 mice were treated with three different activators each for AhR, CAR, PXR, PPAR, and Nrf2. In general, the Gsts are readily induced. All five transcription factors appear to play a role in Gst induction. The Nrf2 activators induced most Gsts (10), followed by the CAR, PXR and PPAR activators (6-7), whereas the AhR ligands induced the least (1). Clofibrate, a PPAR agonist, induced most of the Gsts; however, all three PPAR agonists decreased Gstp1/2 mRNA. None of the 15 inducers was able to increase, or only minimally increased eight of the Gsts (Gsta3, Gstk1, Gstm6, Gsto1, Gstp1/2, Gstt3, Gstz1, MGst1). Thus, the protection afforded by a ligand for one of these transcription factors will depend on the activator, as well as which Gst that detoxifies the chemicals of interest.
Key Words: Glutathione S-transferase; GST; induction; mRNA; bDNA.
1 The opinions expressed in this article are the authors’ personal opinions and do not necessarily reflect those of FDA, DHHS, or the Federal Government
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. L. Yeager, S. A. Reisman, L. M. Aleksunes, and C. D. Klaassen Introducing the "TCDD-Inducible AhR-Nrf2 Gene Battery" Toxicol. Sci., October 1, 2009; 111(2): 238 - 246. [Abstract] [Full Text] [PDF]
|
|