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.
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.
Authors: Raju Khatri; Preeti Shah; Rupa Guha; Feyruz V Rassool; Alan E Tomkinson; Angela Brodie; Anil K Jaiswal Journal: Mol Cancer Ther Date: 2015-05-14 Impact factor: 6.261
Authors: Patricia Rada; Ana I Rojo; Anika Offergeld; Gui Jie Feng; Juan P Velasco-Martín; José Manuel González-Sancho; Ángela M Valverde; Trevor Dale; Javier Regadera; Antonio Cuadrado Journal: Antioxid Redox Signal Date: 2014-12-09 Impact factor: 8.401
Authors: Jonathan A Zweig; Mikah S Brandes; Barbara H Brumbach; Maya Caruso; Kirsten M Wright; Joseph F Quinn; Amala Soumyanath; Nora E Gray Journal: Neurobiol Aging Date: 2020-12-25 Impact factor: 4.673
Authors: Sandra Vomund; Anne Schäfer; Michael J Parnham; Bernhard Brüne; Andreas von Knethen Journal: Int J Mol Sci Date: 2017-12-20 Impact factor: 5.923
Authors: Danielle R Bruns; Joshua C Drake; Laurie M Biela; Frederick F Peelor; Benjamin F Miller; Karyn L Hamilton Journal: Oxid Med Cell Longev Date: 2015-10-25 Impact factor: 6.543