A role for metals and free radicals in the induction of apoptosis in thymocytes

Wolfe, James T.; Ross, David; Cohen, Gerald M.

doi:10.1016/0014-5793(94)00920-1

Cited by 163 publications

(87 citation statements)

References 53 publications

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“…This can occur by an increase in ROS production or a decrease in the ability of the cell to metabolize them. 10 Results from other studies are consistent with a critical role for ROS in dexamethasoneinduced lymphocytes apoptosis: (1) exogenous treatment of thymocytes with chemical antioxidants or antioxidant enzymes protects against dexamethasone-induced apoptosis; 8,11 ± 16 (2) treatment with metal chelators has been shown to inhibit this type of cell death; 11,17 (3) culture of thymocytes under hypoxic conditions generally affords protection from dexamethasone; 8,15,18 and (4) lipid peroxidation, as a measure of oxidative damage, is seen after glucocorticoid treatment in thymocytes 19 and S49.1 lymphocytes. 20 Whether ROS are important as signals in apoptosis or produced only during the execution phase is far from clear (see discussion in 21 ± 23 ).…”

Section: Introductionmentioning

confidence: 55%

“…48 Thymocytes are also protected by divalent ion chelators consistent with a role for the interaction of ROS and metals in Fenton-type chemistry during glucocorticoid-mediated apoptosis. 11 A number of studies have shown that decreased concentrations of reduced glutathione accompany steroid-induced apoptosis, 7,12 ± 14,19 suggesting that cellular redox state is perturbed during this process. Increases in lipid peroxidation after glucocorticoid treatment, as a measurement of oxidative damage, are also seen in thymocytes 19 and S49.1 lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

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Thymocytes selected for resistance to hydrogen peroxide show altered antioxidant enzyme profiles and resistance to dexamethasone-induced apoptosis

Tome

Briehl

2001

Cell Death Differ

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Treatment of WEHI7.2 cells, a mouse thymoma-derived cell line, with dexamethasone, a synthetic glucocorticoid, causes the cells to undergo apoptosis. Previous work has shown that treatment of WEHI7.2 cells with dexamethasone results in a downregulation of antioxidant defense enzymes, suggesting that increased oxidative stress may play a role in glucocorticoid-induced apoptosis. To test whether resistance to oxidative stress causes resistance to dexamethasoneinduced apoptosis, WEHI7.2 cell variants selected for resistance to 50, 100 and 200 mM H 2 O 2 were developed. Resistance to H 2 O 2 is accompanied by increased antioxidant enzyme activity, resistance to other oxidants and a delayed loss of viable cells after dexamethasone treatment. In the 200 mM H 2 O 2 -resistant cell variant the delay in cell loss is correlated with delayed release of cytochrome c from the mitochondria into the cytosol. This suggests that reactive oxygen species play a role in a signaling event during steroidmediated apoptosis in lymphocytes. Cell Death and Differentiation (2001) 8, 953 ± 961.

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Section: Introductionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Thymocytes selected for resistance to hydrogen peroxide show altered antioxidant enzyme profiles and resistance to dexamethasone-induced apoptosis

Tome

Briehl

2001

Cell Death Differ

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“…This discrepancy may be due to the presence of splicing variants or some other technical problems. In some cell lines, bcl-2-overexpressing cells show greater resistance to various pro-oxidants than do mock-transfected cells [41][42][43]. However, in other cell lines, expression of bcl-2 does not protect the transfected cells against oxidative stress [44,45].…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling of diabetic and galactosaemic cataractous rat lens by microarray analysis

2005

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Aims/hypothesis: Osmotic and oxidative stress is associated with the progression and advancement of diabetic cataract. In the present study, we used a cDNA microarray method to analyse gene expression patterns in streptozotocininduced diabetic rats and galactose-fed cataractous lenses. In addition, we investigated the regulation and interaction(s) of anti-oxidant protein 2 and lens epithelium-derived growth factor in these models. Methods: To identify differential gene expression patterns, one group of Sprague-Dawley rats was made diabetic with streptozotocin and a second group was made galactosaemic. Total RNA was extracted from the lenses of both groups and their controls. Labelled cDNAwas hybridised to Atlas Rat Arrays. Changes in gene expression level were analysed. Real-time PCR and western analysis were used to validate the microarray results. Results: The expression of 31 genes was significantly modulated in hyperglycaemic lenses compared with galactosaemic lenses. Notably, transcript and protein levels of B-cell leukaemia/ lymphoma protein 2 and nuclear factor-κB were significantly elevated in rat lenses at 4 weeks after injection of streptozotocin. At a later stage, mRNA and protein levels of TGF-β were elevated. However, levels of mRNA for IGF-1, lens epithelium-derived growth factor and anti-oxidant protein 2 were diminished in streptozotocin-induced diabetic cataract. Conclusions/interpretations: These results provide evidence that progression of sugar cataract involves oxidativeand TGF-β-mediated signalling. These pathways may promote abnormal gene expression in the hyperglycaemic and galactosaemic states and thus may contribute to the symptoms associated with these conditions. Since oxidative stress seems to be a major event in cataract formation, supply of anti-oxidant may postpone the progression of such disorders.

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“…To investigate the mechanism of NF B activation by daunorubicin, compounds were employed which included PDTC which has both antioxidant and metal chelating properties, and previously has been shown to inhibit the activation of NF B mediated by H 2 O 2 (19). Another inhibitor utilized, deferoxamine (desferal), can interfere with the production of oxygen radicals, in particular OH radicals generated in the presence of catalytic amounts of transition metals (the Fenton reaction), by preferentially chelating iron ions (30). Both compounds inhibited daunorubicin-induced NF B activation and B-linked gene expression.…”

Section: Discussionmentioning

confidence: 99%

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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A role for metals and free radicals in the induction of apoptosis in thymocytes

Cited by 163 publications

References 53 publications

Thymocytes selected for resistance to hydrogen peroxide show altered antioxidant enzyme profiles and resistance to dexamethasone-induced apoptosis

Thymocytes selected for resistance to hydrogen peroxide show altered antioxidant enzyme profiles and resistance to dexamethasone-induced apoptosis

Gene expression profiling of diabetic and galactosaemic cataractous rat lens by microarray analysis

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

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