Antioxidant Responsive Element - Explore the Science & Experts | ideXlab

Scan Science and Technology

Contact Leading Edge Experts & Companies

Antioxidant Responsive Element

The Experts below are selected from a list of 1962 Experts worldwide ranked by ideXlab platform

Antioxidant Responsive Element – Free Register to Access Experts & Abstracts

Jeffrey A Johnson – One of the best experts on this subject based on the ideXlab platform.

  • Nrf2, a multi-organ protector?
    The FASEB Journal, 2005
    Co-Authors: Jiang Li, Delinda A Johnson, Thor D. Stein, Andrew D. Kraft, Marcus J. Calkins, Rebekah J. Jakel, Jeffrey A Johnson
    Abstract:

    NF-E2-related factor 2 (Nrf2) is a basic leucine zipper transcription factor that binds to the promoter sequence “Antioxidant Responsive Element (ARE)” leading to coordinated up-regulation of ARE-driven detoxification and Antioxidant genes. Since the expression of a wide array of Antioxidant and detoxification genes are positively regulated by the ARE sequence, Nrf2 may serve as a master regulator of the ARE-driven cellular defense system against oxidative stress. In support of this, numerous studies have shown that Nrf2 protects many cell types and organ systems from a broad spectrum of toxic insults and disease pathpathogenesis. This Nrf2-conferred, multi-organ protection phenomenon raises an interesting question about how a single protein can protect many different organs from various toxic insults. A possible molecular mechanism explaining this phenomenon is that Nrf2 protects many different cell types by coordinately up-regulating classic ARE-driven genes as well as cell type-specific target genes that a…

  • Dissecting tBHQ induced ARE-driven gene expression through long and short oligonucleotide arrays
    Physiological Genomics, 2004
    Co-Authors: Jiang Li, Maria L. Spletter, Jeffrey A Johnson
    Abstract:

    This paper compares the gene expression profiles identified by short (Affymetrix U95AV2) or long (Agilent Hu1A) oligonucleotide arrays on a model for upregulation of a cluster of Antioxidant Responsive Element-driven genes by treatment with tert -butylhydroquinone. MAS 5.0, dCHIP, and RMA were applied to normalize the Affymetrix data, and Lowess regression was considered for Agilent data. SAM was used to identify the differential gene expression. A set of biological markers and housekeeping genes were chosen to evaluate the performance of multiple normalization approaches. Both arrays illustrated a definite set of overlapping genes between the data sets regardless of data mining tools used. However, unique gene expression profiles based on the platform used were also revealed and confirmed by quantitative RT-PCR. Further analysis of the data revealed by alternative approaches suggested that alternative splicing, multiple vs. single probe(s) measurement, and use or nonuse of mismatch probes may account for the discrepant data. Therefore, these two microarray technologies offer relatively reliable data. Integration of the gene expression profiles from different array platforms may not only help for cross-validation but also provide a more complete view of the transcriptional scenario.

  • Targeted disruption of Nrf2 causes regenerative immune-mediated hemolytic anemia
    Proceedings of the National Academy of Sciences of the United States of America, 2004
    Co-Authors: Kaimin Chan, Jeffrey A Johnson
    Abstract:

    A basic leucine zipper transcription factor, NF-E2-related factor 2 (Nrf2), plays a critical role in the cellular defense mechanism by mediating a coordinate up-regulation of Antioxidant Responsive Element-driven detoxification and Antioxidant genes. Here, we report that targeted disruption of Nrf2 causes regenerative immune-mediated hemolytic anemia due to increased sequestration of damaged erythrocytes. Splenomegaly and spleen toxicity in Nrf2-/- mice raised a possibility of hemolytic anemia and splenic extramedullary hemahematopoiesis in Nrf2-/- mice. In support of this, hematology analysis revealed that Nrf2-/- mice suffer from anemia with abnormal red cell morphologies (i.e., Howell-Jolly bodies, acantocytes, and schistocytes). In addition, Nrf2-/- erythrocytes were more sensitive to H2O2-induced hemolysis, and erythrocyte-bound IgG levels were markedly increased in Nrf2-/- mice compared with Nrf2+/+ mice. Because IgG bound to erythrocytes in the presence of oxidative damage in erythrocytes (regardless of Nrf2 genotype), these data support that Nrf2-/- erythrocytes have higher levels of damage compared with Nrf2+/+ cells. Finally, Nrf2-/- mice showed increased levels of erythrocyte-bound IgG compared with Nrf2+/+ mice after H2O2 injection in vivo, suggesting that the decreased glutathione and increased H2O2 render the Nrf2-/- mice more susceptible to toxicity. Taken together, these observations indicate that a chronic increase in oxidative stress due to decreased Antioxidant capacity sensitizes erythrocytes and causes hemolytic anemia in Nrf2-/- mice, suggesting a pivotal role of Nrf2-Antioxidant Responsive Element pathway in the cellular Antioxidant defense system.

C. B. Pickett – One of the best experts on this subject based on the ideXlab platform.

Janean M Hanson – One of the best experts on this subject based on the ideXlab platform.

  • nrf2 not the estrogen receptor mediates catechol estrogen induced activation of the Antioxidant Responsive Element
    Biochimica et Biophysica Acta, 2003
    Co-Authors: Peter C Anderson, Janette K Padgitt, Janean M Hanson, Christopher M Waters, Jeffrey A Johnson
    Abstract:

    Abstract The Antioxidant Responsive Element (ARE) plays an important role in the gene expression of phase II detoxification enzymes, such as NAD(P)H:quinone oxidoreductase 1 (NQO1), and NF-E2-related factor2 (Nrf2) is the transcription factor for the ARE-driven genes. Interestingly, estrogen receptor (ER) was reported to increase NQO1 gene expression through the ARE. In this study, we investigated the role of ER and Nrf2 in ARE activation using IMR-32 cells and mouse primary astrocytes. Among tested estrogen-related compounds, only catechol estrogens (i.e. 4-hydroxyestradiol) activated the ARE. Since 4-hydroxyestradiol-induced ARE activation was not inhibited by either 17β-estradiol or tamoxifen, and overexpression of ER-α decreased 4-hydroxyestradiol-induced ARE activation, ARE activation by catechol estrogen was independent of ER. Nrf2, however, was very important in the 4-hydroxyestradiol-induced ARE activation. 4-Hydroxyestradiol did not activate the ARE in Nrf2 knockout (−/−) primary astrocytes, but did activate the ARE when Nrf2 was transfected into Nrf2−/− astrocytes. In addition, dominant negative Nrf2 completely blocked 4-hydroxyestradiol-induced ARE activation in Nrf2+/+ astrocytes, and only 4-hydroxyestradiol induced Nrf2 nuclear translocation in IMR-32 cells. A selective phosphatidylinositol 3-kinase (PI3-kinase) inhibitor (LY294002) blocked 4-hydroxyestradiol-induced Nrf2 nuclear translocation and NQO1 activity induction in IMR-32 cells. Taken together, these observations suggest that 4-hydroxyestradiol activates the ARE by a PI3-kinase-Nrf2 dependent mechanism, not involving ER.

  • Nrf2, not the estrogen receptor, mediates catechol estrogen-induced activation of the Antioxidant Responsive Element.
    Biochimica et biophysica acta, 2003
    Co-Authors: Peter C Anderson, Janette K Padgitt, Janean M Hanson, Christopher M Waters, Jeffrey A Johnson
    Abstract:

    The Antioxidant Responsive Element (ARE) plays an important role in the gene expression of phase II detoxification enzymes, such as NAD(P)H:quinone oxidoreductase 1 (NQO1), and NF-E2-related factor2 (Nrf2) is the transcription factor for the ARE-driven genes. Interestingly, estrogen receptor (ER) was reported to increase NQO1 gene expression through the ARE. In this study, we investigated the role of ER and Nrf2 in ARE activation using IMR-32 cells and mouse primary astrocytes. Among tested estrogen-related compounds, only catechol estrogens (i.e. 4-hydroxyestradiol) activated the ARE. Since 4-hydroxyestradiol-induced ARE activation was not inhibited by either 17beta-estradiol or tamoxifen, and overexpression of ER-alpha decreased 4-hydroxyestradiol-induced ARE activation, ARE activation by catechol estrogen was independent of ER. Nrf2, however, was very important in the 4-hydroxyestradiol-induced ARE activation. 4-Hydroxyestradiol did not activate the ARE in Nrf2 knockout (-/-) primary astrocytes, but did activate the ARE when Nrf2 was transfected into Nrf2-/- astrocytes. In addition, dominant negative Nrf2 completely blocked 4-hydroxyestradiol-induced ARE activation in Nrf2+/+ astrocytes, and only 4-hydroxyestradiol induced Nrf2 nuclear translocation in IMR-32 cells. A selective phosphatidylinositol 3-kinase (PI3-kinase) inhibitor (LY294002) blocked 4-hydroxyestradiol-induced Nrf2 nuclear translocation and NQO1 activity induction in IMR-32 cells. Taken together, these observations suggest that 4-hydroxyestradiol activates the ARE by a PI3-kinase-Nrf2 dependent mechanism, not involving ER.

  • phosphatidylinositol 3 kinase not extracellular signal regulated kinase regulates activation of the Antioxidant Responsive Element in imr 32 human neuroblastoma cells
    Journal of Biological Chemistry, 2001
    Co-Authors: Janean M Hanson, Jeffrey A Johnson
    Abstract:

    Abstract The AntioxidantResponsive Element (ARE) plays an important role in the induction of phase II detoxifying enzymes including NADPH:quinone oxidoreductase (NQO1). We report herein that activation of the human NQO1-ARE (hNQO1-ARE) bytert-butylhydroquinone (tBHQ) is mediated by phosphatidylinositol 3-kinase (PI3-kinase), not extracellular signal-regulated kinase (Erk1/2), in IMR-32 human neuroblastoma cells. Treatment with tBHQ significantly increased NQO1 protein without activation of Erk1/2. In addition, PD 98059 (a selective mitogen-activated kinase/Erk kinase inhibitor) did not inhibit hNQO1-ARE-luciferase expression or NQO1 protein induction by tBHQ. Pretreatment with LY 294002 (a selective PI3-kinase inhibitor), however, inhibited both hNQO1-ARE-luciferase expression and endogenous NQO1 protein induction. In support of a role for PI3-kinase in ARE activation we show that: 1) transfection of IMR-32 cells with constitutively active PI3-kinase selectively activated the ARE in a dose-dependent manner that was completely inhibited by treatment with LY 294002; 2) pretreatment of cells with the PI3-kinase inhibitors, LY 294002 and wortmannin, significantly decreased NF-E2-related factor 2 (Nrf2) nuclear translocation induced by tBHQ; and 3) ARE activation by constitutively active PI3-kinase was blocked completely by dominant negative Nrf2. Taken together, these data clearly show that ARE activation by tBHQ depends on PI3-kinase, which lies upstream of Nrf2.

Zhiyue Wang – One of the best experts on this subject based on the ideXlab platform.

Eun Young Park – One of the best experts on this subject based on the ideXlab platform.