TY - JOUR
T1 - Analysis of the role of Nrf2 in the expression of liver proteins in mice using two-dimensional gel-based proteomics
AU - Abdullah, A.
AU - Kitteringham, N.R.
AU - Jenkins, R.E.
AU - Goldring, C.
AU - Higgins, L.
AU - Yamamoto, M.
AU - Hayes, J.
AU - Park, B.K.
N1 - Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84866136122&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:84866136122
SN - 1734-1140
VL - 64
SP - 680
EP - 697
JO - Pharmacological Reports
JF - Pharmacological Reports
IS - 3
ER -