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

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

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Authors

  • A. Abdullah
  • N.R. Kitteringham
  • R.E. Jenkins
  • C. Goldring
  • L. Higgins
  • M. Yamamoto
  • J. Hayes
  • B.K. Park

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Original languageEnglish
Pages680-697
Number of pages18
JournalPharmacological Reports
Journal publication date2012
Journal number3
Volume64
StatePublished

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. Copyright © 2012 by Institute of Pharmacology Polish Academy of Sciences.

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