Analysis of the role of Nrf2 in the expression of liver proteins in mice using two-dimensional gel-based proteomics

Azman Abdullah, Neil R. Kitteringham, Rosalind E. Jenkins, Christopher Goldring, Larry Higgins, Masayuki Yamamoto, John Hayes, B. Kevin Park

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Background: The transcription factor Nrf2 regulates expression of multiple cellular defence proteins through the antioxidant response element (ARE). Nrf2-deficient mice (Nrf2-/-) are highly susceptible to xenobiotic-mediated toxicity, but it is not known whether this reflects low basal expression or reduced inducibility of Nrf2-regulated genes in response to chemical insults. Methods: Wild type and Nrf2-/- mice were fed diet supplemented with the established Nrf2 inducer butylated hydroxyanisole (BHA) [0.5% (w/w)] for 14 days. To define the range of Nrf2-regulated proteins, both basally and following exposure to BHA, a comparison of the liver proteomes of Nrf2-/- and wild type mice was conducted. The two-dimensional gel electrophoresis (2-DE) technique and MALDI mass spectrometry were utilized in the attempt to define Nrf2-regulated proteins. Results: Overall, 24 proteins were identified, which were regulated either basally (3 proteins), inducibly (16 proteins), or both (5 proteins). These included several well-established Nrf2-driven gene products e.g., aldo-keto reductase and glutathione transferases. Multiple consensus ARE/ARE-like sequences were found in the Nrf2-regulated genes. Conclusions: This study confirms the central role of Nrf2 in the induction of multiple defense proteins as well as its control in the constitutive expression of certain proteins.

Original languageEnglish
Pages (from-to)680-697
Number of pages18
JournalPharmacological Reports
Volume64
Issue number3
DOIs
Publication statusPublished - 2012
Externally publishedYes

Keywords

  • Liver
  • Mouse
  • Nrf2
  • Protein expression
  • Transgenic
  • Two-dimensional gel electrophoresis

ASJC Scopus subject areas

  • Pharmacology

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