Role of Conformation of Peroxynitrite Anion (ONOO-) with Its Stability and Toxicity

Tsai, Jyh-Hsin Michael; Harrison, Joseph G.; Martin, J. C.; Hamilton, Tracy P.; Woerd, Mark van der; Jablonsky, Michael J.; Beckman, Joseph S.

doi:10.1021/ja00088a072

Cited by 119 publications

(119 citation statements)

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“…Assuming that formation of ONO 2 CO 2 Ϫ is indeed essential for peroxynitrite-triggered tyrosine nitration as suggested by Ber- (48). Based on this information, we propose the scheme shown in Fig.…”

Section: Resultsmentioning

confidence: 61%

Lack of Tyrosine Nitration by Peroxynitrite Generated at Physiological pH

Pfeiffer

Mayer

1998

Journal of Biological Chemistry

167

123

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Nitration of tyrosine residues of proteins has been suggested as a marker of peroxynitrite-mediated tissue injury in inflammatory conditions. The nitration reaction has been extensively studied in vitro by bolus addition of authentic peroxynitrite, an experimental approach hardly reflecting in vivo situations in which the occurrence of peroxynitrite is thought to result from continuous generation of Nitric oxide ( ⅐ NO) 1 is a cellular messenger regulating numerous biological processes, including relaxation of blood vessels and neurotransmitter release in the brain, but overproduction of ⅐ NO appears to contribute essentially to tissue injury in inflammatory and ischemic conditions (1). The molecular mechanisms underlying the cytotoxicity of ⅐ NO are not well understood. The potent oxidant peroxynitrite, which is formed in a rapid reaction from ⅐ NO and O 2 . , is thought to be a key mediator of ⅐ NO toxicity in atherosclerosis, congestive heart failure, glutamate excitotoxicity, and other disease states involving inflammatory oxidative stress (2). Formation of peroxynitrite from ⅐ NO and O 2 . occurs at nearly diffusion-controlled rates (4.3-6.7 ϫ 10 9 M Ϫ1 s Ϫ1 ) (3, 4). Therefore, ⅐ NO out-competes the reaction of O 2. with superoxide dismutase at steady-state concentrations that are likely to occur in vivo (5). Peroxynitrite is stable at alkaline pH but has a half-life of less than 1 s at pH 7.4 (pK a ϭ 6.8) (6). Depending on the pH, the corresponding peroxynitrous acid either rearranges to NO 3 Ϫ or decomposes to NO 2 Ϫ and O 2 (7). Peroxynitrite has been shown to react with virtually all classes of biomolecules (8). The reaction with phenolic compounds, including free and protein-bound tyrosine, results in the formation of nitrated, hydroxylated, and dimeric products (9 -12). The nitration of tyrosine, yielding mainly 3-nitrotyrosine, is markedly enhanced by CO 2 , which reacts with peroxynitrite anion at physiological pH to form the potent nitrating species ONO 2 CO 2 Ϫ (13-15). Tyrosine nitration appears to represent a prominent pathway of pathophysiological protein modification under inflammatory conditions associated with increased expression and/or activity of ⅐ NO synthases (16). Based on the detection of nitrotyrosine, peroxynitrite has been suggested to be involved in the pathology of a wide range of diseases, including neurodegenerative diseases (17, 18), acute lung injury (19), atherosclerosis (20, 21), bacterial and viral infections (22, 23), and chronic inflammation (24).Peroxynitrite-triggered tyrosine nitration has been extensively studied in vitro by bolus addition of alkaline solutions of peroxynitrite to tyrosine-containing samples. However, this experimental approach does not reflect the in vivo situation in which peroxynitrite is thought to be formed by the rapid reaction of ⅐ NO with O 2 . at physiological pH. Intriguingly, we 2 and others (12) found that the nitrating potential of the sydnonimine-based nitrovasodilator SIN-1, which releases ⅐ NO and O 2 . at the same time (25), is ...

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Section: Resultsmentioning

confidence: 61%

Lack of Tyrosine Nitration by Peroxynitrite Generated at Physiological pH

Pfeiffer

Mayer

1998

Journal of Biological Chemistry

167

123

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“…ONOO -exhibits • OH radical-like reactivity derived from the vibrationally exciting state of probably less stable trans-ONOOH (Tsai et al 1994). Hyaluronan does not undergo the degradation by…”

Section: Hyaluronan Susceptibility To Peroxynitrite Oxidative Actionmentioning

confidence: 99%

Pro-oxidative effect of peroxynitrite regarding biological systems: a special focus on high-molar-mass hyaluronan degradation

Hrabárová¹,

Juránek²,

Šoltés³

2011

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Abstract. Current understanding on the role of peroxynitrite in etiology and pathogenesis of some human diseases, such as cardio-vascular diseases, stroke, cancer, inflammation, neurodegenerative disorders, diabetes mellitus and diabetic complications has recently led to intensive investigation of peroxynitrite involvement in physiology and pathophysiology.Mechanism of cytotoxic effects of peroxynitrite involve its reactions with lipids, DNA/RNA, proteins, and polysaccharides, thus triggering cellular responses ranging from subtle changes of cell functioning to severe oxidative damage of the affected macromolecules leading to necrosis or apoptosis. The present work is aimed at providing a brief overview of i) peroxynitrite biosynthesis and reaction pathways in vivo, ii) its synthetic preparation in vitro, and iii) to reveal its potential damaging role in vivo, on actions studied via monitoring in vitro hyaluronan degradation. The complex biochemical behavior of peroxynitrite is determined by a number of variables, such as chemistry of the reaction itself, depending mostly on the involvement of conformational structures of different energy states, concentration of the species involved, content of reactive intermediates and trace transition metal ions, contribution of carbon dioxide, presence of trace organics, and by the reaction kinetics. Recently, in vitro studies of oxidative cleavage of hyaluronan have, in fact, been the subject of growing interest. Here we also describe our experimental set-up for studying peroxynitrite-mediated degradation of hyaluronan, a system, which may be suitable for testing prospective pharmacological substances.

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“…Peroxynitrite in alkaline solution is present only in the cis conformation (28,29), which contributes to the unusual stability of peroxynitrite by preventing the rearrangement of the terminal oxygen to form nitrate (NO 3 Ϫ ). Curiously, peroxynitrite in the solid state is entirely in the cis conformation (28,30). The x-ray structure of the tetramethylammonium salt of peroxynitrite has recently been determined and was also in the cis conformation (31).…”

mentioning

confidence: 99%

Superoxide Reacts with Nitric Oxide to Nitrate Tyrosine at Physiological pH via Peroxynitrite

Reiter

Teng

Beckman

2000

Journal of Biological Chemistry

Self Cite

368

238

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Tyrosine nitration is a widely used marker of peroxynitrite (ONOO ؊ ) produced from the reaction of nitric oxide with superoxide. Pfeiffer and Mayer (Pfeiffer, S., and Mayer, B. (1998) J. Biol. Chem. 273, 27280 -27285) reported that superoxide produced from hypoxanthine plus xanthine oxidase in combination with nitric oxide produced from spermine NONOate did not nitrate tyrosine at neutral pH. They suggested that nitric oxide and superoxide at neutral pH form a less reactive intermediate distinct from preformed alkaline peroxynitrite that does not nitrate tyrosine. Using a stopped-flow spectrophotometer to rapidly mix potassium superoxide with nitric oxide at pH 7.4, we report that an intermediate spectrally and kinetically identical to preformed alkaline cis-peroxynitrite was formed in 100% yield. Furthermore, this intermediate nitrated tyrosine in the same yield and at the same rate as preformed peroxynitrite. Equivalent concentrations of nitric oxide under aerobic conditions in the absence of superoxide did not produce detectable concentrations of nitrotyrosine. Carbon dioxide increased the efficiency of nitration by nitric oxide plus superoxide to the same extent as peroxynitrite. In experiments using xanthine oxidase as a source of superoxide, tyrosine nitration was substantially inhibited by urate formed from hypoxanthine oxidation, which was sufficient to account for the lack of tyrosine nitration previously reported. We conclude that peroxynitrite formed from the reaction of nitric oxide with superoxide at physiological pH remains an important species responsible for tyrosine nitration in vivo.

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Role of Conformation of Peroxynitrite Anion (ONOO-) with Its Stability and Toxicity

Cited by 119 publications

References 5 publications

Lack of Tyrosine Nitration by Peroxynitrite Generated at Physiological pH

Lack of Tyrosine Nitration by Peroxynitrite Generated at Physiological pH

Pro-oxidative effect of peroxynitrite regarding biological systems: a special focus on high-molar-mass hyaluronan degradation

Superoxide Reacts with Nitric Oxide to Nitrate Tyrosine at Physiological pH via Peroxynitrite

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Role of Conformation of Peroxynitrite Anion (ONOO-) with Its Stability and Toxicity

Cited by 119 publications

References 5 publications

Lack of Tyrosine Nitration by Peroxynitrite Generated at Physiological pH

Lack of Tyrosine Nitration by Peroxynitrite Generated at Physiological pH

Pro-oxidative effect of peroxynitrite regarding biological systems: a special focus on high-molar-mass hyaluronan degradation

Superoxide Reacts with Nitric Oxide to Nitrate Tyrosine at Physiological pH via Peroxynitrite

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Pro-oxidative effect of peroxynitrite regarding biological systems: a special focus on high-molar-mass hyaluronan degradation