Nitric oxide (NO) protects against cellular damage by reactive oxygen species

Wink, David A.; Cook, John A.; Pacelli, Roberto; Liebmann, James; Krishna, Murali C.; Mitchell, James B.

doi:10.1016/0378-4274(95)03557-5

Cited by 157 publications

(74 citation statements)

References 15 publications

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“…We were unable to detect 3-nitrotyrosine by Western blot analysis from total cell lysates in any of the samples (data not shown) consistent with previous reports (12). These findings reconfirm the important antioxidant rather than pro-oxidant properties of NO (43).…”

Section: No Protects Cells From Osupporting

confidence: 81%

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Superoxide Fluxes Limit Nitric Oxide-induced Signaling

Thomas

Ridnour

Espey

et al. 2006

Journal of Biological Chemistry

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105

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Independently, superoxide (O 2 ؊) and nitric oxide (NO) are biologically important signaling molecules. When co-generated, these radicals react rapidly to form powerful oxidizing and nitrating intermediates. Although this reaction was once thought to be solely cytotoxic, herein we demonstrate using MCF7, macrophage, and endothelial cells that when nanomolar levels of NO and O 2 ؊ were produced concomitantly, the effective NO concentration was established by the relative fluxes of these two radicals. Differential regulation of sGC, pERK, HIF-1␣, and p53 were used as biological dosimeters for NO concentration. Introduction of intracellular-or extracellular-generated O 2 ؊ during NO generation resulted in a concomitant increase in oxidative intermediates with a decrease in steady-state NO concentrations and a proportional reduction in the levels of sGC, ERK, HIF-1␣, and p53 regulation. NO responses were restored by addition of SOD. The intermediates formed from the reactions of NO with O 2 ؊ were non-toxic, did not form 3-nitrotyrosine, nor did they elicit any signal transduction responses. H 2 O 2 in bolus or generated from the dismutation of O 2 ؊ by SOD, was cytotoxic at high concentrations and activated p53 independent of NO. This effect was completely inhibited by catalase, suppressed by NO, and exacerbated by intracellular catalase inhibition. We conclude that the reaction of O 2 ؊ with NO is an important regulatory mechanism, which modulates signaling pathways by limiting steady-state levels of NO and preventing H 2 O 2 formation from O 2 ؊ .

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Section: No Protects Cells From Osupporting

confidence: 81%

“…11 summarizes our results. NO alone was nontoxic at 100 M Sper/NO consistent with other reports (43,44). The cytoxicity of H 2 O 2 alone was completely prevented by the addition of NO.…”

Section: No Protects Cells From Osupporting

confidence: 80%

Superoxide Fluxes Limit Nitric Oxide-induced Signaling

Thomas

Ridnour

Espey

et al. 2006

Journal of Biological Chemistry

Self Cite

105

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“…In WT mice, it appears that NO serves a protective function in the liver, as treatment with aminoguanidine, an inhibitor of iNOS, leads to weight loss and severe liver damage during the acute stage of the infection (30). One possible mechanism by which NO could protect the liver involves the scavenging of the ROI that are generated in response to eggs (31,54). Specifically, NO can compete with SOD for O 2 Ϫ , form ONOO Ϫ , and thus reduce the levels of hydrogen peroxide produced after the dismutation of O 2 Ϫ by SOD.…”

Section: Discussionmentioning

confidence: 99%

IL-4 Plays a Crucial Role in Regulating Oxidative Damage in the Liver During Schistosomiasis

Flamme

Patton

Bauman

et al. 2001

The Journal of Immunology

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Liver enlargement and hepatocyte proliferation, normal responses in wild-type (WT) mice infected with the parasitic helminth Schistosoma mansoni, were found to be severely impaired in infected IL-4−/− mice. Compared with WT mice, increased levels of O2−, NO, and the more highly reactive ONOO− were detected in the liver and produced by lesional cells isolated from liver granulomas of infected IL-4−/− mice. Concurrently, antioxidant defenses in the liver, specifically catalase levels, diminished dramatically during the course of infection in these animals. This contrasted to the situation in infected WT mice, where catalase levels remained as high as those in normal mice. Actual levels of reactive oxygen and nitrogen intermediates in the livers of infected IL-4−/− animals are thus likely to be considerably higher than those in the livers of infected WT mice. To determine whether these changes contributed to the development of the more severe disease that characterizes infection in the IL-4−/− animals, we treated infected IL-4−/− mice with uric acid, a potent scavenger of ONOO−. This resulted in significantly increased hepatocyte proliferation, decreased morbidity, and prolonged survival. Taken together, these data indicate that IL-4 is playing a protective role during schistosomiasis by controlling the tight regulation of the generation of reactive oxygen and nitrogen intermediates in the liver.

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“…70 In kiwifruit, the ROS effects were significantly reversed by NO via genetic upregulation of SOD and CAT, and suppression of LOX resulting in the maintenance of vitamins C and E. 70 Further, NO's role as an antioxidant has been ascribed for its property of preventing the Fenton's reaction, making the meager formation of hydroxyl radical. 97 Likewise, NO affects the functioning of plant POD involved in cell wall lignification since it easily forms an iron-nitrosyl complex with haem iron. 98 Free radical scavenging ability of NO has been demonstrated to preferentially quench o-quinone radicals, causing interruption of normal browning reactions occurring at the cut surfaces of fruit.…”

Section: Role Of No In Post-climacteric Biochemical Eventsmentioning

confidence: 99%