Effects of peroxynitrite‐induced protein modifications on tyrosine phosphorylation and degradation

Gow, Andrew J.; Durán, Daniel; Malcolm, Stuart; Ischiropoulos, Harry

doi:10.1016/0014-5793(96)00347-x

Cited by 427 publications

(264 citation statements)

References 24 publications

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“…The biological significance of many of these findings awaits the demonstration of reversibility (and the mechanism thereof) and quantitative evaluation of the degree of inhibition under physiological and pathophysiological endogenous conditions of ONOO À generation. It may be, as previously suggested, that tyrosine nitration marks the protein for proteolytic degradation (Gow et al, 1996;Ischiropoulos, 1998;Souza et al, 2000).…”

Section: Protein Tyrosine-nitrationmentioning

confidence: 57%

“…Formation of protein 3-nitrotyrosine has been detected in a number of disease states, but the functions of this protein modification remain unclear. Although there is some suggestion of reversibility, there is no convincing molecular evidence for a eucaryotic denitrase (Gow et al, 1996;Kamisaki et al, 1998). There appears to be some selectivity in the nitration, since not all proteins in a tissue under analysis are nitrated.…”

Section: Protein Tyrosine-nitrationmentioning

confidence: 99%

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Biological chemistry of reactive oxygen and nitrogen and radiation-induced signal transduction mechanisms

2003

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In the past few years, nuclear DNA damage-sensing mechanisms activated by ionizing radiation have been identified, including ATM/ATR and the DNA-dependent protein kinase. Less is known about sensing mechanisms for cytoplasmic ionization events and how these events influence nuclear processes. Several studies have demonstrated the importance of cytoplasmic signaling pathways in cytoprotection and mutagenesis. For cytoplasmic signaling, radiation-stimulated reactive oxygen species (ROS) and reactive nitrogen species (RNS) are essential activators of these pathways. This review summarizes recent studies on the chemistry of radiation-induced ROS/ RNS generation and emphasizes interactions between ROS and RNS and the relative roles of cellular ROS/ RNS generators as amplifiers of the initial ionization events. Cellular mechanisms for regulating ROS/RNS levels are discussed. The mechanisms by which cells sense ROS/RNS are examined in terms of how ROS/RNS modify protein structure and function, for example, interactions with metal-thiol clusters, protein tyrosine nitration, protein cysteine oxidation, S-thiolation and Snitrosylation. We propose that radiation-induced ROS are the initiators and that nitric oxide (NO ) or derivatives are the effectors activating these signal transduction pathways. In responding to cellular ionization events, the cell converts an oxidative signal to a nitrosative one because ROS are too reactive and unspecific in their reactions for regulatory purposes and the cell is equipped to precisely modulate NO levels.

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Section: Protein Tyrosine-nitrationmentioning

confidence: 57%

Section: Protein Tyrosine-nitrationmentioning

confidence: 99%

Biological chemistry of reactive oxygen and nitrogen and radiation-induced signal transduction mechanisms

2003

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“…Peroxynitrite can form stable 3-nitrotyrosine by the addition of a nitro group to the 3-position adjacent to the hydroxyl group of the tyrosine (8). Nitration by peroxynitrite inhibits IL-8 binding to neutrophils (9), C1q binding on human IgG (10), and protein phosphorylation by tyrosine kinase (11). Peroxynitrite is produced by the reaction between NO and superoxide (12,13).…”

mentioning

confidence: 99%

Enhanced Activity of Human IL-10 After Nitration in Reducing Human IL-1 Production by Stimulated Peripheral Blood Mononuclear Cells

Freels

Nelson

Hoyt

et al. 2002

The Journal of Immunology

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Nitric oxide and superoxide form the unstable compound, peroxynitrite, which can nitrate proteins and compromise function of proinflammatory cytokines at sites of inflammation. Reduced function of proinflammatory proteins such as IL-8, macrophage inflammatory protein-1α, and eotaxin suggest an anti-inflammatory effect of nitration. The effects of nitration on anti-inflammatory cytokines such as IL-10 are unknown. We hypothesized that peroxynitrite would modify the function of anti-inflammatory cytokines like IL-10. To test this hypothesis, the capacity of recombinant human IL-10 to inhibit production of human IL-1β (IL-1) from LPS-stimulated human PBMC was evaluated. Human IL-10 was nitrated by incubation with peroxynitrite or by incubation with 3-morpholinosydnonimine, a peroxynitrite generator, for 2 h and then incubated with LPS-stimulated PBMC for 6 h, and IL-1 was measured in the culture supernatant fluids. Human IL-1 production was significantly lower in the peroxynitrite- or 3-morpholinosydnonimine-nitrated IL-10 group than in the IL-10 controls (p < 0.05, all comparisons). This finding demonstrates that although peroxynitrite inhibits proinflammatory cytokines, it may augment anti-inflammatory cytokines and further point to an important role for peroxynitrite in the regulation of inflammation.

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“…However, PN also nitrates phenols such as tyrosine and phenylalanine that affects cellular function [134,263,264]. Protein nitration may interfere with protein phosphorylation signaling pathways with recent studies showing that nitrated proteins form in platelets undergoing collagen-induced aggregation [265][266][267]. Low, Sabetkar et al examined the effects of PN on platelet function and to further understand the role of the NO-cGMP pathway and protein nitration in washed platelets and in platelet-rich plasma from human volunteers [268].…”

Section: Anti-platelet Aggregation Effects Of Peroxynitritementioning

confidence: 99%

Potential Benefits of Peroxynitrite

Nossaman

Kadowitz²

2008

TOPHARMJ

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Peroxynitrite (PN) is generated by the reaction of nitric oxide (NO) and superoxide in one of the most rapid reactions in biology. Studies have reported that PN is a cytotoxic molecule that contributes to vascular injury in a number of disease states. However, it has become apparent that PN has beneficial effects including vasodilation, inhibition of platelet aggregation, inhibition of inflammatory cell adhesion, and protection against ischemia/reperfusion injury in the heart. It is our hypothesis that PN may serve to inactivate superoxide and prolong the actions of NO in the circulation. This manuscript reviews the beneficial effects of PN in the cardiovascular system. Keywords:Nitric oxide/*metabolism, nitric oxide synthase/metabolism/physiology, peroxynitrous acid/metabolism, reactive nitrogen species/metabolism, reactive oxygen species/metabolism, endothelium, vascular/drug effects/metabolism, muscle, smooth, vascular/drug effects/*metabolism, vasodilator agents/adverse effects, oxidative stress/*physiology, vasodilation/drug effects.

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Effects of peroxynitrite‐induced protein modifications on tyrosine phosphorylation and degradation

Cited by 427 publications

References 24 publications

Biological chemistry of reactive oxygen and nitrogen and radiation-induced signal transduction mechanisms

Biological chemistry of reactive oxygen and nitrogen and radiation-induced signal transduction mechanisms

Enhanced Activity of Human IL-10 After Nitration in Reducing Human IL-1 Production by Stimulated Peripheral Blood Mononuclear Cells

Potential Benefits of Peroxynitrite

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