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

First Author  Abdullah A Year  2012
Journal  Pharmacol Rep Volume  64
Issue  3 Pages  680-97
PubMed ID  22814021 Mgi Jnum  J:329801
Mgi Id  MGI:6879765 Doi  10.1016/s1734-1140(12)70863-0
Citation  Abdullah A, et al. (2012) Analysis of the role of Nrf2 in the expression of liver proteins in mice using two-dimensional gel-based proteomics. Pharmacol Rep 64(3):680-97
abstractText  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.
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