Redox signalling by transcription factors NF-κB and AP-1 in lymphocytes

Schulze‐Osthoff, Klaus; Łos, Marek; Baeuerle, Patrick A.

doi:10.1016/0006-2952(95)02011-z

Cited by 253 publications

(153 citation statements)

References 64 publications

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“…In this regard, NF B is considered to be an oxidative stress-responsive transcription factor (17) and interestingly, daunorubicin itself can be reductively metabolized to a semi-quinone radical intermediate (2) which further participates in reactions which give rise to ROS. The single-electron reduction of daunorubicin is catalyzed by a number of cellular enzymes, including cytochrome P450, the flavin NADPH-cytochrome p450 reductases, NADH-cytochrome b 5 reductase, and mitochondrial NADH dehydrogenase (2).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, ROS are generated through its participation in futile/redox cycling. Reactive oxygen species have previously been implicated in the mechanism of NF B activation in response to cytokines, phorbol esters, and bacterial toxins (17,18). Conclusions have been drawn from studies using modulators of signaling events with antioxidant and metal chelating properties (18,19,21), and the overexpression of enzymes such as catalase and superoxide dismutase (20).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to ceramide being implicated as an upstream regulator of I B␣ phosphorylation, a model has been proposed whereby reactive oxygen species (ROS) act as second messengers in this event (17). Evidence to support this model is based on the ability of H 2 O 2 to activate NF B (18) and the inhibitory effects of antioxidants such as N-acetylcysteine (a thiol antioxidant and glutathione precursor) and pyrrolidine dithiocarbamate (PDTC), which is also a metal chelator, on NF B activation (18 -21).…”

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confidence: 99%

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Daunorubicin Activates NFκB and Induces κB-dependent Gene Expression in HL-60 Promyelocytic and Jurkat T Lymphoma Cells

Boland

Foster

O’Neill

1997

Journal of Biological Chemistry

115

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The anthracycline antibiotic, daunorubicin, can induce programmed cell death (apoptosis) in cells. Recent work suggests that this event is mediated by ceramide via enhanced ceramide synthase activity. Since the generation of ceramide has been directly linked with the activation of the transcription factor, NF B, this was investigated as a novel target for the action of daunorubicin. Here we describe how treatment of HL-60 promyelocytes and Jurkat T lymphoma cells with daunorubicin results in the activation of the transcription factor NF B. The effect of daunorubicin was evident following 1-2 h treatment, which was in contrast to the time course of activation obtained with the cytokine, tumor necrosis factor, where NF B activation was detected within minutes of cellular stimulation. Activated complexes were shown to contain predominantly p50 and p65/RelA subunit components. Daunorubicin also induced I B degradation and increased the expression of an NF B-linked reporter gene. In addition, the drug was found to strongly potentiate the ability of tumor necrosis factor to induce an NF B-linked reporter gene, suggesting a synergy between these two agents in this response. These events were sensitive to the iron chelator, deferoxamine mesylate (desferal), and the anti-oxidant and metal chelator pyrrolidine dithiocarbamate. A structurally related compound, mitoxantrone, which, unlike daunorubicin, is unable to undergo redox cycling in cells, also activated NF B in a pyrrolidine dithiocarbamate-sensitive manner. A specific inhibitor of ceramide synthase, fumonisin B1, had no effect on daunorubicin induced NF B activation at a range of concentrations previously reported to block apoptosis induced by this drug. However, this agent could inhibit increases in ceramide induced by daunorubicin, in addition to blocking ceramide synthase activity from HL-60 cells which was activated in response to daunorubicin treatment. These data therefore suggest that the effect of daunorubicin on NF B is unlikely to involve ceramide, but may involve reactive oxygen species generated as a result of endogenous cellular processes rather than reductive metabolism of the drug. As NF B may be involved in apoptosis, this effect may be an important aspect of the cellular responses to this agent.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Daunorubicin Activates NFκB and Induces κB-dependent Gene Expression in HL-60 Promyelocytic and Jurkat T Lymphoma Cells

Boland

Foster

O’Neill

1997

Journal of Biological Chemistry

115

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“…Another regulatory element in the promoter region was indicated by the presence of two sites for an NF-κB-like element at k714 and k1104. NF-κB activation, in contrast to AP-1 activation [43], has been shown to be inhibited by anti-oxidants [44]. The possibility of interactions between the transcription factors that bind to both AP-1 and NF-κB sites has been previously demonstrated in the human GSTP1-1 gene [42] and will be explored in the rat GSTA3 subunit gene.…”

Section: Exon Length (Bp)mentioning

confidence: 99%

Genomic cloning and characterization of the rat glutathione S-transferase-A3-subunit gene

Fotouhi‐Ardakani

Batist

1999

Biochemical Journal

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The rat glutathione S-transferase-A3-subunit (GSTA3) gene is a member of the class Alpha GSTs, which we have previously reported to be overexpressed in anti-cancer-drug-resistant cells. In this study, we report the isolation and characterization of the entire rat GSTA3 (rGST Yc " ) subunit gene. The rat GSTA3 subunit gene is approximately 15 kb in length and consists of seven exons interrupted by introns of different lengths. Exon 1, with a length of 219 bp, contains only the 5h-untranslated region of the gene. Each exon-intron splicing junction exhibited the consensus sequence for a mammalian splice site. The transcription start site and exon 1 of rat GSTA3 were characterized by a combination of primer extension and rapid amplification of the cDNA ends. Position j1 was identified 219 bp upstream of the first exon-intron splicing junction. The proximal promoter region of the rat GSTA3 subunit gene does not contain typical TATA or CAAT boxes. A computer-based search for potential transcription-factor binding sites revealed the existence of a

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“…It has been proposed that the activation of PTKs by costimulation induces a novel lipidforming cascade that could also produce reactive oxygen intermediates (ROIs) [4]. These might then act as second messengers regulating the activity of protein kinases or phosphatases or alternatively, directly modify the functional domains of transcription factors [5].NF-B is a transcription factor that participates in the expression of a specific set of genes involved in cellular growth and differentiation. This factor has a central role in inflammatory responses and T cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

CD28-mediated activation in CD45RA+ and CD45RO+ T cells: enhanced levels of reactive oxygen intermediates and c-Rel nuclear translocation in CD45RA+ cells

Lahdenpohja

Hurme

1998

Journal of Leukocyte Biology

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Redox signalling by transcription factors NF-κB and AP-1 in lymphocytes

Cited by 253 publications

References 64 publications

Daunorubicin Activates NFκB and Induces κB-dependent Gene Expression in HL-60 Promyelocytic and Jurkat T Lymphoma Cells

Daunorubicin Activates NFκB and Induces κB-dependent Gene Expression in HL-60 Promyelocytic and Jurkat T Lymphoma Cells

Genomic cloning and characterization of the rat glutathione S-transferase-A3-subunit gene

CD28-mediated activation in CD45RA+ and CD45RO+ T cells: enhanced levels of reactive oxygen intermediates and c-Rel nuclear translocation in CD45RA+ cells

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