Nitric oxide induces the apoptosis of human BCR-ABL-positive myeloid leukemia cells: evidence for the chelation of intracellular iron

Ferry-Dumazet, Hélène; Mamani-Matsuda, Maria; Dupouy, Maryse; Belloc, Françis; Thiolat, Denis; Marit, Gérald; Arock, Michel; Reiffers, Josy; Mossalayi,

doi:10.1038/sj.leu.2402404

Cited by 30 publications

(12 citation statements)

References 41 publications

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“…Thus, the addition of SNP or other iron compounds efficiently protected various tumor cells from NO-mediated growth inhibition and apoptosis (7,8). Furthermore, SNP rescued hypoxia-induced death of C6 glioma cells via the iron-dependent activation of the Na ϩ -Ca 2ϩ exchanger (1).…”

Section: Discussionmentioning

confidence: 99%

Sodium Nitroprusside Promotes IRP2 Degradation via an Increase in Intracellular Iron and in the Absence of S Nitrosylation at C178

Wang

Fillebeen

Chen

et al. 2006

Molecular and Cellular Biology

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In iron-replete cells the posttranscriptional regulator IRP2 undergoes ubiquitination and proteasomal degradation. A similar response occurs in cells exposed to sodium nitroprusside (SNP), an NO-releasing drug. It has been proposed that nitroprusside ([Fe(CN) 5 NO]2؊ ) fails to donate iron into cells and that it promotes IRP2 degradation via S nitrosylation at C178. This residue is located within a stretch of 73 amino acids, earlier proposed to define an iron-dependent degradation domain. Surprisingly, we show that IRP2 bearing a C178S mutation or a ⌬73 deletion is sensitive to degradation not only by ferric ammonium citrate (FAC) but also by SNP. Moreover, FAC and SNP attenuate the RNA-binding activities of IRP2 and its homologue IRP1 with similar kinetics. Actinomycin D, cycloheximide, succinylacetone, and dimethyl-oxalylglycine antagonize IRP2 degradation in response to both FAC and SNP, suggesting a common mechanistic basis. IRP2 is not only sensitive to fresh, but also to photodegraded SNP and remains unaffected by S-nitrosoglutathione (GSNO), an established nitrosation agent. Importantly, both fresh and photodegraded SNP, but not GSNO, promote a >4-fold increase in the calcein-accessible labile iron pool. Collectively, these results suggest that IRP2 degradation by SNP does not require S nitrosylation but rather represents a response to iron loading.Iron regulatory proteins, IRP1 and IRP2, are posttranscriptional regulators of iron metabolism (13, 32). They coordinately control the expression of mRNAs containing iron-responsive elements (IREs), such as those encoding transferrin receptor 1 (TfR1) and ferritin. In iron-deficient cells, IRPs are activated for high-affinity IRE-binding, and IRE-IRP interactions stabilize TfR1 mRNA and inhibit ferritin mRNA translation. These homeostatic responses stimulate acquisition of extracellular iron via TfR1 and prevent its storage in ferritin.IRPs control the expression of additional IRE-containing mRNAs encoding proteins with crucial functions in body iron homeostasis, such as the erythroid-specific enzyme of the heme biosynthetic pathway aminolevulinate synthase 2 and the iron transporters ferroportin 1 and DMT1 (13, 32). IRP1/IRP2 double-knockout mice exhibit early embryonic lethality (38). The targeted inactivation of IRP1 has yielded only minor phenotypic abnormalities in the kidney and in brown fat (29), whereas the disruption of IRP2 has been associated with a progressive adult onset neurodegenerative disorder (28) and/or microcytosis (5, 10).Experiments with IRP1 Ϫ/Ϫ and IRP2 Ϫ/Ϫ cells showed that IRP1 and IRP2 have similar iron-sensing capacities under typical tissue culture conditions with 21% oxygen; however, when oxygen concentration was reduced to 3 to 6%, which is believed to mimic physiological conditions in tissues, only IRP2 responded to alterations in iron levels (30). It appears that under these conditions (30) and in animal tissues (29), IRP1 predominates in the cytosolic aconitase form and does not very efficiently respond to iron deficiency, whic...

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Section: Discussionmentioning

confidence: 99%

Sodium Nitroprusside Promotes IRP2 Degradation via an Increase in Intracellular Iron and in the Absence of S Nitrosylation at C178

Wang

Fillebeen

Chen

et al. 2006

Molecular and Cellular Biology

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“…Nitric oxide (NO) has been shown to be involved in apoptosis signaling pathway in many diseases, such as anemia of chronic diseases [7], aplastic anemia [8] and leukemia [9]. NO is synthesized from L -arginine by NO synthase (NOS), which exists in three isoforms, namely, neuronal NOS, inducible NOS (iNOS) and endothelial NOS [10,11,12].…”

Section: Introductionmentioning

confidence: 99%

Cytokine-Induced Apoptosis of Beta-Thalassemia/Hemoglobin E Erythroid Progenitor Cells via Nitric Oxide-Mediated Process in vitro

Kheansaard

Panichob²,

Fucharoen³

et al. 2011

Acta Haematol

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Background/Aim: β-Thalassemia/hemoglobin E (β-thal/HbE) is a common hereditary anemia in Thailand. Ineffective erythropoiesis due to apoptosis and decreased lifespan of circulating thalassemic red blood cells are the major causes of anemia. Changes to bone marrow microenvironment could contribute to apoptotic events. This study examined the effects of cytokines interleukin-1β, tumor necrosis factor-α and interferon-γ on apoptosis of β-thal/HbE erythroid progenitor cells in vitro, including nitric oxide-mediated apoptotic processes. Methods: Percent apoptosis of erythroid progenitor cells from 5 β-thal/HbE patients and 5 normal control subjects was examined using flow cytometry. In addition, the inducible nitric oxide synthase (iNOS) mRNA level and nitrite production were measured using quantitative PCR and the Griess method, respectively. Results: Upon cytokine treatment, a higher percent apoptosis was obtained with β-thal/HbE erythroid progenitor cells compared with control, and the maximum effect was observed using 20 ng/ml interferon-γ on day 14 of culture. There was an increase in iNOS mRNA level and a concomitant elevation of nitrite concentration in culture medium. Apoptosis and nitrite level were abrogated when β-thal/HbE and control cells were treated with S-methylisothiourea sulfate, an iNOS inhibitor. Conclusion: The marked sensitivity of erythroid progenitor cells from β-thal/HbE patients to cytokine-induced apoptosis via an NO-mediated process reflects a proapoptotic status of such thalassemic red blood cells.

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“…However, at high concentrations, nitroxide radicals may be formed and cause damage to the local environment (Morehouse et al, 1987). Other clinical uses for DFX include cancer therapies (Becton and Bryles, 1988;Lee and Wurster, 1995;Ferry-Dumazet et al, 2002;Buss et al, 2003;Dayani et al, 2004;Brard et al, 2006). Kim et al (2002) and Choi et al (2003) have shown that p38 MAP kinase plays an important role in the DFX-mediated death of HL-60 cells, and that downregulation of the p38 kinase pathway by the cAMP response element-binding protein protects HL-60 cells from DFX-induced apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Desferrioxamine (DFX) has genotoxic effects on cultured human lymphocytes and induces the p53-mediated damage response

et al. 2007

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Nitric oxide induces the apoptosis of human BCR-ABL-positive myeloid leukemia cells: evidence for the chelation of intracellular iron

Cited by 30 publications

References 41 publications

Sodium Nitroprusside Promotes IRP2 Degradation via an Increase in Intracellular Iron and in the Absence of S Nitrosylation at C178

Sodium Nitroprusside Promotes IRP2 Degradation via an Increase in Intracellular Iron and in the Absence of S Nitrosylation at C178

Cytokine-Induced Apoptosis of Beta-Thalassemia/Hemoglobin E Erythroid Progenitor Cells via Nitric Oxide-Mediated Process in vitro

Desferrioxamine (DFX) has genotoxic effects on cultured human lymphocytes and induces the p53-mediated damage response

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