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, Azman
AU - Kitteringham, Neil R.
AU - Jenkins, Rosalind E.
AU - Goldring, Christopher
AU - Higgins, Larry
AU - Yamamoto, Masayuki
AU - Hayes, John
AU - Park, B. Kevin
N1 - Funding Information:
This work was supported by the MRC Proteomics Initiative Award (UK). Azman Abdullah would like to thank the Ministry of Science, Technology and Innovation (MOSTI) of the Government of Malaysia as well as the National University of Malaysia (UKM) for sponsoring his doctoral studies at the University of Liverpool.
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.
KW - Liver
KW - Mouse
KW - Nrf2
KW - Protein expression
KW - Transgenic
KW - Two-dimensional gel electrophoresis
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U2 - 10.1016/S1734-1140(12)70863-0
DO - 10.1016/S1734-1140(12)70863-0
M3 - Article
C2 - 22814021
AN - SCOPUS:84866136122
SN - 1734-1140
VL - 64
SP - 680
EP - 697
JO - Polish Journal of Pharmacology and Pharmacy
JF - Polish Journal of Pharmacology and Pharmacy
IS - 3
ER -