Acceleration of Peroxynitrite Oxidations by Carbon Dioxide

Uppu, Rao M.; Squadrito, G; Pryor, William A.

doi:10.1006/abbi.1996.0131

Cited by 295 publications

(220 citation statements)

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“…The peroxynitrite anion combine with carbon dioxide to form nitroso peroxycarbonate adduct, a known fastest reaction [10]. On decomposition it forms NO 3 -and CO 2 .…”

Section: (A) Diffusionmentioning

confidence: 99%

Biochemistry of Nitric Oxide

2011

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Nitric oxide (NO) a free radical having both cytoprotective as well as tumor promoting agent is formed from L-arginine by converting it to L-citrulline via nitric oxide synthase enzymes. The reaction product of nitric oxide with superoxide generates potent oxidizing agent, peroxynitrite which is the main mediator of tissue and cellular injury. Peroxynitrite is reactive towards many biomolecules which includes amino acids, nucleic acid bases; metal containing compounds, etc. NO metabolites may play a key role in mediating many of the genotoxic/ carcinogenic effects as DNA damage, protein or lipid modification, etc. The basic reactions of nitric oxide can be divided as direct effect of the radical where it alone plays a role in either damaging or protecting the cell milieu and an indirect effect in which the byproducts of nitric oxide formed by convergence of two independent radical generating pathways play the role in biological reactions which mainly involve oxidative and nitrosative stress. Nitric oxide is also capable of directly interacting with mitochondria through inhibition of respiration or by permeability transition. Reaction of nitric oxide with metal ions include its direct interaction with the metals or with oxo complexes thereby reducing them to lower valent state. Excessive production of nitric oxide can be studied by inhibiting the synthetic pathway of nitric oxide using both selective or specific nitric oxide synthase inhibitor or nonselective nitric oxide synthase inhibitor with respect to isoforms of nitric oxide.Keywords Nitric oxide Á Nitric oxide synthase Á Nitric oxide inhibitors Á Generation of nitric oxide Á Cancer Á Systemic lupus erythematosus Á Direct and indirect effect of nitric oxide Á Effect of nitric oxide on mitochondria

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“…The peroxynitrite anion combine with carbon dioxide to form nitroso peroxycarbonate adduct, a known fastest reaction [10]. On decomposition it forms NO 3 -and CO 2 .…”

Section: (A) Diffusionmentioning

confidence: 99%

Biochemistry of Nitric Oxide

2011

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“…The effects of UA on tyrosine nitration in the presence and absence of NaHCO 3 were compared, as the nitrating activity of ONOO Ϫ is enhanced in the presence of carbonyl anion, which is found in a biological milieu (29,30). At levels comparable to those found in the sera of normal humans (5 mg/dl), UA effectively inhibited the SIN-1-mediated nitration of tyrosine residues in BSA and various FBS proteins regardless of whether or not carbonyl anion was present (Fig.…”

Section: Capacity Of Ua To Inhibit Onoo ϫ Reactivity In Vitromentioning

confidence: 99%

The Peroxynitrite Scavenger Uric Acid Prevents Inflammatory Cell Invasion into the Central Nervous System in Experimental Allergic Encephalomyelitis through Maintenance of Blood-Central Nervous System Barrier Integrity

Kean

Spitsin

Mikheeva

et al. 2000

The Journal of Immunology

145

113

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Uric acid (UA), a product of purine metabolism, is a known scavenger of peroxynitrite (ONOO−), which has been implicated in the pathogenesis of multiple sclerosis and experimental allergic encephalomyelitis (EAE). To determine whether the known therapeutic action of UA in EAE is mediated through its capacity to inactivate ONOO− or some other immunoregulatory phenomenon, the effects of UA on Ag presentation, T cell reactivity, Ab production, and evidence of CNS inflammation were assessed. The inclusion of physiological levels of UA in culture effectively inhibited ONOO−-mediated oxidation as well as tyrosine nitration, which has been associated with damage in EAE and multiple sclerosis, but had no inhibitory effect on the T cell-proliferative response to myelin basic protein (MBP) or on APC function. In addition, UA treatment was found to have no notable effect on the development of the immune response to MBP in vivo, as measured by the production of MBP-specific Ab and the induction of MBP-specific T cells. The appearance of cells expressing mRNA for inducible NO synthase in the circulation of MBP-immunized mice was also unaffected by UA treatment. However, in UA-treated animals, the blood-CNS barrier breakdown normally associated with EAE did not occur, and inducible NO synthase-positive cells most often failed to reach CNS tissue. These findings are consistent with the notion that UA is therapeutic in EAE by inactivating ONOO−, or a related molecule, which is produced by activated monocytes and contributes to both enhanced blood-CNS barrier permeability as well as CNS tissue pathology.

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“…3, bottom). Previous reports suggest that the rate at which peroxynitrite is added to a solution containing tyrosine can drastically alter the nitration yield (8,9,15,22,23,32,33). A bolus addition of increasing concentrations of peroxynitrite showed a significant increase in formation of NO 2 -Y-8 (Fig.…”

Section: Peroxynitrite-dependent Oxidation and Nitration Of Tyrosyl Pmentioning

confidence: 99%