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Keywords {🔍}

open, window, cells, citation, differentiation, nrf, science, web, google, scholar, expression, pubmed, aml, fig, wtnrf, cell, levels, protein, dnnrf, treatment, activity, transcription, glutathione, cancer, leukemia, pef, vdr, control, effects, agents, shown, human, induction, combination, acid, vitamin, effect, factor, dca, nrfare, clones, myeloid, data, activation, response, pathway, figure, carnosic, role, γgcsh,

Topics {✒️}

wright-giemsa-stained cytospin smears wright-giemsa-stained cytospin preparations glutathione-s-transferase ya subunit peroxidase-conjugated donkey anti-rabbit nf-e2-related factor2 mutant γgcsh-arem-luc construct m-mulv reverse transcriptase γgcsh-are4-luc reporter construct phosphatidylinositol 3-kinase/akt pathway cullin-ring ubiquitin ligases including γgcsh-are4-luc activation differentiation-related transcription factors empty vector-expressing cells google scholar ben-dor google scholar simboli-campbell double-stranded odn carrying phosphatidylinositol 3-kinase/akt tre-luc reporter assay perk-dependent cell survival thermo-start master mix vdre-luc reporter construct dominant-negative mutant nrf2m γ-gcs protein levels vdrex6-luc reporter assay β-naphthoflavone-induced expression catechol-type electrophilic compound nrf2/antioxidant response element vitamin d-regulated gene rabin medical cenetr tpa-stimulated superoxide production nmol o2−/106 cells/min vdre-luc reporter activity significantly transactivate tre-luc intracellular oxidation/reduction status twitter page taylor γgcsh-are4-luc reporters increased dna-binding capacity relative tre-luc activity 25d/ca-treated u937 cells empty vector-transfected cells dominant negative c-jun relative vdre-luc activity french-american-british classification exploiting cellular pathways hvdr-derived tre sequence runx2-dependent transcriptional activation γgcs heavy subunit tpa-stimulated superoxide generation nrf2-keap1 antioxidant response post-transcriptionally activating nrf2

Questions {❓}

• Dietary chemopreventive phytochemicals: too little or too much?

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      name: The Nrf2 transcription factor is a positive regulator of myeloid differentiation of acute myeloid leukemia cells
      headline: The Nrf2 transcription factor is a positive regulator of myeloid differentiation of acute myeloid leukemia cells
      abstract:1α,25-dihydroxyvitamin D3 (1,25D) is a powerful differentiation agent, which has potential for treatment of acute myeloid leukemia (AML), but induces severe hypercalcemia at pharmacologically active doses. We have previously shown that carnosic acid (CA), the polyphenolic antioxidant from rosemary plant, markedly potentiates differentiation induced by low concentrations of 1,25D in human AML cell lines. Here, we demonstrated similar enhanced differentiation responses to the 1,25D/CA combination in primary leukemic cells derived from patients with AML, and determined the role of the Nrf2/antioxidant response element (Nrf2/ARE) pathway in these effects using U937 human monoblastic leukemia cells as the model. CA strongly transactivated the ARE-luciferase reporter gene, induced the ARE-responsive genes, NADP(H)-quinone oxidoreductase and the γ-glutamylcysteine synthetase heavy subunit, and elevated cellular glutathione levels. Interestingly, 1,25D potentiated the effects of CA on these activities. Stable transfection of wild-type (wt) Nrf2 resulted in the enhancement, while transfection of dominant-negative (dn) Nrf2 produced suppression of differentiation induced by the 1,25D/CA combination and, surprisingly, by 1,25D alone. These opposite effects were associated with a corresponding increase or decrease in vitamin D receptor and retinoid X receptor-α protein levels, and in vitamin D responsive element transactivation. Cells transfected with wtNrf2 and dnNrf2 also displayed opposing changes in the levels of the AP-1 family proteins (c-Jun and ATF2) and AP-1 transcriptional activity. Pretreatment with AP-1 decoy oligodeoxynucleotide markedly attenuated the differentiation in wtNrf2-transfected cells, suggesting that the pro-differentiation action of Nrf2 is mediated by functional AP-1. Our findings suggest that the Nrf2/ARE pathway plays an important part in the cooperative induction of myeloid leukemia cell differentiation by 1,25D and a plant polyphenol.
      description:1α,25-dihydroxyvitamin D3 (1,25D) is a powerful differentiation agent, which has potential for treatment of acute myeloid leukemia (AML), but induces severe hypercalcemia at pharmacologically active doses. We have previously shown that carnosic acid (CA), the polyphenolic antioxidant from rosemary plant, markedly potentiates differentiation induced by low concentrations of 1,25D in human AML cell lines. Here, we demonstrated similar enhanced differentiation responses to the 1,25D/CA combination in primary leukemic cells derived from patients with AML, and determined the role of the Nrf2/antioxidant response element (Nrf2/ARE) pathway in these effects using U937 human monoblastic leukemia cells as the model. CA strongly transactivated the ARE-luciferase reporter gene, induced the ARE-responsive genes, NADP(H)-quinone oxidoreductase and the γ-glutamylcysteine synthetase heavy subunit, and elevated cellular glutathione levels. Interestingly, 1,25D potentiated the effects of CA on these activities. Stable transfection of wild-type (wt) Nrf2 resulted in the enhancement, while transfection of dominant-negative (dn) Nrf2 produced suppression of differentiation induced by the 1,25D/CA combination and, surprisingly, by 1,25D alone. These opposite effects were associated with a corresponding increase or decrease in vitamin D receptor and retinoid X receptor-α protein levels, and in vitamin D responsive element transactivation. Cells transfected with wtNrf2 and dnNrf2 also displayed opposing changes in the levels of the AP-1 family proteins (c-Jun and ATF2) and AP-1 transcriptional activity. Pretreatment with AP-1 decoy oligodeoxynucleotide markedly attenuated the differentiation in wtNrf2-transfected cells, suggesting that the pro-differentiation action of Nrf2 is mediated by functional AP-1. Our findings suggest that the Nrf2/ARE pathway plays an important part in the cooperative induction of myeloid leukemia cell differentiation by 1,25D and a plant polyphenol.
      author:
            type:Person
            name:Victoria Novik
            type:Person
            name:Joseph Levy
            type:Person
            name:Irene Bobilev
            type:Person
            name:Ofer Shpilberg
            type:Person
            name:Yoav Sharoni
            type:Person
            name:Itai Levi
            type:Person
            name:George P. Studzinski
            type:Person
            name:Michael Danilenko
            type:Person
            name:Michael Danilenko
      pageStart:317
      pageEnd:329
      datePublished:2011-02-01
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      name:Joseph Levy
      name:Irene Bobilev
      name:Ofer Shpilberg
      name:Yoav Sharoni
      name:Itai Levi
      name:George P. Studzinski
      name:Michael Danilenko
      name:Michael Danilenko
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