The Chemistry and Tumoricidal Activity of Nitric Oxide/Hydrogen Peroxide and the Implications to Cell Resistance/Susceptibility

Farias‐Eisner, Robin; Chaudhuri, Gautam; Aeberhard, Ernesto E.; Fukuto, Jon M.

doi:10.1074/jbc.271.11.6144

Cited by 147 publications

(82 citation statements)

References 54 publications

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“…Although in animals the reaction of NO with H 2 O 2 does not seem to be generally (and directly) involved in killing, NO cooperates with H 2 O 2 to induce DNA fragmentation and cell lysis in murine lymphoma, hepatoma, and endothelial cells (23,33). In vitro studies suggest that reaction of NO gas with H 2 O 2 produces singlet oxygen or hydroxyl radicals (34).…”

Section: Discussionmentioning

confidence: 99%

“…In vitro studies suggest that reaction of NO gas with H 2 O 2 produces singlet oxygen or hydroxyl radicals (34). Alternatively, the toxicity of NO͞H 2 O 2 may be caused by the production of a potent oxidant formed via a trace metal-, H 2 O 2 -, and NOdependent process (23). The iron liberated from ferritin by NO indeed may promote oxidative stress caused by H 2 O 2 (11,35).…”

Section: Discussionmentioning

confidence: 99%

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Signal interactions between nitric oxide and reactive oxygen intermediates in the plant hypersensitive disease resistance response

Delledonne

Zeier

Marocco

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

970

757

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Nitric oxide (NO) and reactive oxygen intermediates (ROIs) play key roles in the activation of disease resistance mechanisms both in animals and plants. In animals NO cooperates with ROIs to kill tumor cells and for macrophage killing of bacteria. Such cytotoxic events occur because unregulated NO levels drive a diffusionlimited reaction with O 2 ؊ to generate peroxynitrite (ONOO ؊ ), a mediator of cellular injury in many biological systems. Here we show that in soybean cells unregulated NO production at the onset of a pathogen-induced hypersensitive response (HR) is not sufficient to activate hypersensitive cell death. The HR is triggered only by balanced production of NO and ROIs. Moreover, hypersensitive cell death is activated after interaction of NO not with O 2 ؊ but with H 2O2 generated from O2 ؊ by superoxide dismutase. Increasing the level of O 2 ؊ reduces NO-mediated toxicity, and ONOO ؊ is not a mediator of hypersensitive cell death. During the HR, superoxide dismutase accelerates O 2 ؊ dismutation to H2O2 to minimize the loss of NO by reaction with O 2 ؊ and to trigger hypersensitive cell death through NO͞H 2O2 cooperation. However, O2 ؊ rather than H 2O2 is the primary ROI signal for pathogen induction of glutathione S-transferase, and the rates of production and dismutation of O 2 ؊ generated during the oxidative burst play a crucial role in the modulation and integration of NO͞H 2O2 signaling in the HR. Thus although plants and animals use a similar repertoire of signals in disease resistance, ROIs and NO are deployed in strikingly different ways to trigger host cell death.A ttempted infection of plants by an avirulent pathogen elicits a battery of defenses often accompanied by the collapse of challenged host cells. This hypersensitive cell death results in a restricted lesion delimited from surrounding healthy tissue and is thought to contribute to pathogen restriction. An early event in this hypersensitive response (HR) is the generation of superoxide (O 2 Ϫ ) and accumulation of hydrogen peroxide (H 2 O 2 ) in an oxidative burst reminiscent of that producing such reactive oxygen intermediates (ROIs) in activated macrophages (1).Activation of the oxidative burst in the plant HR is part of a highly amplified and integrated signal system that also involves salicylic acid and perturbations of cytosolic Ca 2ϩ to trigger defense mechanisms (2) and to mediate the establishment of systemic immunity (3). The oxidative burst is necessary but not sufficient to trigger host cell death, and recent data indicate that nitric oxide (NO) cooperates with ROIs in the activation of hypersensitive cell death (4).NO and ROIs also interact in the mammalian native immune system where macrophage killing of pathogens and tumor cells involves the diffusion-limited reaction of NO and O 2 to generate ONOO Ϫ , a long lived and highly reactive oxidant species that freely crosses membranes (5), which may modulate NO signal functions (6). ONOO Ϫ induces apoptosis in some human tumor cells (7), and it is also directly cytotoxic...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Signal interactions between nitric oxide and reactive oxygen intermediates in the plant hypersensitive disease resistance response

Delledonne

Zeier

Marocco

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

970

757

View full text Add to dashboard Cite

show abstract

“…Nitric oxide has previously been shown to inhibit purified bovine catalase activity in vitro (Brown 1995b). Nitric oxide donors (SNAP, Deta-NO) have also been shown to inhibit catalase activity in a rat glial cell line (Dobashi et al 1997), human ovarian cancer cells (Farias-Eisner et al 1996), endothelial cells (Hashida et al 2000) and in MRL-lpr/lpr mice prone to autoimmune disease (Keng et al 2000).…”

Section: Discussionmentioning

confidence: 99%

“…De novo synthesis of catalase has been demonstrated to be up-regulated following IL-1 treatment of islets from diabetes-prone BB rats (Sparre et al 2002). However, the enzyme activity of purified catalase in vitro was inhibited by nitric oxide gas directly (Brown 1995b) and cellular catalase was inhibited by treatment with nitric oxide donors (morpho sydnonimine-1 [SIN-1], s-nitroson-acetyl penicillamine [SNAP]) (Farias-Eisner et al 1996, Dobashi et al 1997, Hashida et al 2000.…”

Section: Introductionmentioning

confidence: 99%

Cytokines and nitric oxide inhibit the enzyme activity of catalase but not its protein or mRNA expression in insulin-producing cells

Sigfrid¹,

Cunningham²,

Beeharry³

et al. 2003

Journal of Molecular Endocrinology

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Pancreatic -cells have low activities of the antioxidant enzyme catalase. Nitric oxide interacts with the haem group of catalase inhibiting its activity. We have studied the activity of catalase in -cells under conditions mimicking prediabetes and in which nitric oxide is generated from cytokine treatment in vitro. We also studied whether there is regulation of catalase enzyme activity by nitric oxide at the protein or gene expression level. RINm5F insulin-producing cells, treated for 24 h with cytokines, showed increased medium nitrite production (17±2·2 vs 0·3±0·2 pmol/µg protein) and significantly decreased cellular catalase activity (42·4±4·5%) compared with control cells. A similar reduction was seen in catalase-overexpressing RIN-CAT cells and in rat or human pancreatic islets of Langerhans. Catalase activity was also suppressed by the long-acting nitric oxide donor diethylenetriamine/nitric oxide adduct (Deta-NO) and this inhibition was reversible. The inhibition of catalase activity by cytokines in RINm5F cells was significantly reversed by the addition of the nitric oxide synthase 2 (NOS2) inhibitors nitro monomethylarginine or N-(3-(aminomethyl)benzyl)acetamidine (1400W). Protein expression was found to be unchanged in cytokine-or Deta-NO-treated RINm5F cells, while mRNA expression was marginally increased. We have shown that inhibition of catalase activity by cytokines is nitric oxide dependent and propose that this inhibition may confer increased susceptibility to cytokine-or nitric oxide-induced cell killing.

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“…A ctivated macrophages produce large amounts of nitric oxide (NO), which induces cytostasis and cytotoxicity to tumor cells both in vitro and in vivo (1)(2)(3)(4)(5)(6)(7)(8). Macrophages also play a significant role in host resistance to tumors (7)(8)(9).…”

mentioning

confidence: 99%

Nitric oxide-induced cytostasis and cell cycle arrest of a human breast cancer cell line (MDA-MB-231): Potential role of cyclin D1

Pervin

Singh

Chaudhuri

2001

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

161

115

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DETA-NONOate, a nitric oxide (NO) donor, induced cytostasis in the human breast cancer cells MDA-MB-231, and the cells were arrested in the G 1 phase of the cell cycle. This cytostatic effect of the NO donor was associated with the down-regulation of cyclin D1 and hypophosphorylation of the retinoblastoma protein. No changes in the levels of cyclin E or the catalytic partners of these cyclins, CDK2, CDK4, or CDK6, were observed. This NO-induced cytostasis and decrease in cyclin D1 was reversible for up to 48 h of DETA-NONOate (1 mM) treatment. DETA-NONOate (1 mM) produced a steady-state concentration of 0.5 M of NO over a 24-h period. Synchronized population of the cells exposed to DETANONOate remained arrested at the G 1 phase of the cell cycle whereas untreated control cells progressed through the cell cycle after serum stimulation. The cells arrested at the G 1 phase after exposure to the NO donor had low cyclin D1 levels compared with the control cells. The levels of cyclin E and CDK4, however, were similar to the control cells. The decline in cyclin D1 protein preceded the decrease of its mRNA. This decline of cyclin D1 was due to a decrease in its synthesis induced by the NO donor and not due to an increase in its degradation. We conclude that down-regulation of cyclin D1 protein by DETA-NONOate played an important role in the cytostasis and arrest of these tumor cells in the G 1 phase of the cell cycle.A ctivated macrophages produce large amounts of nitric oxide (NO), which induces cytostasis and cytotoxicity to tumor cells both in vitro and in vivo (1-8). Macrophages also play a significant role in host resistance to tumors (7-9). Tumor cells cocultured with activated macrophages rapidly develop cytostasis, which precedes the cytotoxic effects (5, 10).It has been reported that NO-induced early cytostasis begins with a rapid and reversible inhibition of ribonucleotide reductase (RR) (10). However, the possibility of targets other than RR being involved in the NO-induced long-lasting cytostasis was suggested by other investigators (10). Hydroxyurea, a specific inhibitor of RR (10), decreased thymidine incorporation in cultured cells and, after its removal, the thymidine incorporation rapidly returned to control values. The rate of recovery was much faster after withdrawal of hydroxyurea when compared with the rate of recovery observed in cells that initially were exposed either to activated macrophages or to a NO donor and then kept in a NO-free environment. On this basis, it was suggested that targets other than RR may be responsible for producing long-lasting cytostasis in target cells exposed to NO (5,10,11). This long-lasting cytostasis, therefore, would be associated with metabolic alterations in target cells, producing long-lasting growth inhibition and requiring a longer time for these cells to resume their normal rate of proliferation.Because the precise mechanism(s) by which NO induces this long-lasting cytostasis is not completely known, the present work was undertaken to assess this mechanism(s)...

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The Chemistry and Tumoricidal Activity of Nitric Oxide/Hydrogen Peroxide and the Implications to Cell Resistance/Susceptibility

Cited by 147 publications

References 54 publications

Signal interactions between nitric oxide and reactive oxygen intermediates in the plant hypersensitive disease resistance response

Signal interactions between nitric oxide and reactive oxygen intermediates in the plant hypersensitive disease resistance response

Cytokines and nitric oxide inhibit the enzyme activity of catalase but not its protein or mRNA expression in insulin-producing cells

Nitric oxide-induced cytostasis and cell cycle arrest of a human breast cancer cell line (MDA-MB-231): Potential role of cyclin D1

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