Analysis of the role of Nrf2 in the expression of liver proteins in mice using two-dimensional gel-based proteomics. / Abdullah, A.; Kitteringham, N.R.; Jenkins, R.E.; Goldring, C.; Higgins, L.; Yamamoto, M.; Hayes, J.; Park, B.K.
In: Pharmacological Reports, Vol. 64, No. 3, 2012, p. 680-697.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Analysis of the role of Nrf2 in the expression of liver proteins in mice using two-dimensional gel-based proteomics
A1 - Abdullah,A.
A1 - Kitteringham,N.R.
A1 - Jenkins,R.E.
A1 - Goldring,C.
A1 - Higgins,L.
A1 - Yamamoto,M.
A1 - Hayes,J.
A1 - Park,B.K.
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.
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. Copyright © 2012 by Institute of Pharmacology Polish Academy of Sciences.
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. Copyright © 2012 by Institute of Pharmacology Polish Academy of Sciences.
UR - http://www.scopus.com/inward/record.url?partnerID=yv4JPVwI&eid=2-s2.0-84866136122&md5=8a020f1d730d9c15575853e34a120cb2
M1 - Article
JO - Pharmacological Reports
JF - Pharmacological Reports
SN - 1734-1140
IS - 3
VL - 64
SP - 680
EP - 697
ER -