A stable solid that generates hydroxyl radical upon dissolution in aqueous solutions: reaction with proteins and nucleic acid

King, Peter; Anderson, V. E.; Edwards, John O.; Gustafson, Gary; Plumb, Robert C.; Suggs, J. William

doi:10.1021/ja00039a068

Cited by 236 publications

(118 citation statements)

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“…4). As previously reported (22)(23)(24)(25)(26)(27), peroxynitrite caused a marked increase in DNA single strand breakage in the J774 cells (Fig. 5).…”

Section: Fig 1 Effect Of Meg Ged S-methyl-meg and Aminoguanidinesupporting

confidence: 88%

“…Although the biological activity and decomposition of peroxynitrite are very much dependent on cellular or chemical environment (concentration of proteins, thiols, glucose, and carbon dioxide and the ratio of NO to superoxide) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11), peroxynitrite is now generally considered a more toxic species than either NO or superoxide anion alone (12)(13)(14)(15)(16)(17)(18)(19). The cytotoxic processes triggered by peroxynitrite include initiation of lipid peroxidation (5,15,16), inhibition of mitochondrial respiration (5,12,(17)(18)(19), inhibition of membrane pumps (20), depletion of glutathione (21), and damage to DNA (22)(23)(24)(25) with subsequent activation of poly(ADP-ribose) synthetase and concomitant cellular energy depletion (25)(26)(27).…”

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confidence: 99%

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Mercaptoethylguanidine and Guanidine Inhibitors of Nitric-oxide Synthase React with Peroxynitrite and Protect against Peroxynitrite-induced Oxidative Damage

Szabó

Ferrer-Sueta

Zingarelli

et al. 1997

Journal of Biological Chemistry

160

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Nitric oxide (NO) produced by the inducible nitricoxide synthase (iNOS) is responsible for some of the pathophysiological alterations during inflammation. Part of NO-related cytotoxicity is mediated by peroxynitrite, an oxidant species produced from NO and superoxide. Aminoguanidine and mercaptoethylguanidine (MEG) are inhibitors of iNOS and have anti-inflammatory properties. Here we demonstrate that MEG and related compounds are scavengers of peroxynitrite. MEG caused a dose-dependent inhibition of the peroxynitrite-induced oxidation of cytochrome c 2؉ , hydroxylation of benzoate, and nitration of 4-hydroxyphenylacetic acid. MEG reacts with peroxynitrite with a second-order rate constant of 1900 ؎ 64 M ؊1 s ؊1 at 37°C. In cultured macrophages, MEG reduced the suppression of mitochondrial respiration and DNA single strand breakage in response to peroxynitrite. MEG also reduced the degree of vascular hyporeactivity in rat thoracic aortic rings exposed to peroxynitrite. The free thiol plays an important role in the scavenging effect of MEG. Aminoguanidine neither affected the oxidation of cytochrome c 2؉ nor reacted with ground state peroxynitrite, but inhibited the peroxynitrite-induced benzoate hydroxylation and 4-hydroxyphenylacetic acid nitration, indicating that it reacts with activated peroxynitrous acid or nitrogen dioxide. Compounds that act both as iNOS inhibitors and peroxynitrite scavengers may be useful anti-inflammatory agents.Nitric oxide (NO), 1,2 a free radical produced by a family of isoenzymes termed nitric-oxide synthases (NOS), has been implicated in a variety of physiological and pathophysiological processes. The cytotoxic effects of NO are mediated in part by peroxynitrite (ONOO Ϫ ), 3 a reactive oxidant species formed from NO and superoxide at an almost diffusion-controlled rate (1-4). Although the biological activity and decomposition of peroxynitrite are very much dependent on cellular or chemical environment (concentration of proteins, thiols, glucose, and carbon dioxide and the ratio of NO to superoxide) (1-11), peroxynitrite is now generally considered a more toxic species than either NO or superoxide anion alone (12-19). The cytotoxic processes triggered by peroxynitrite include initiation of lipid peroxidation (5, 15, 16), inhibition of mitochondrial respiration (5,12,(17)(18)(19), inhibition of membrane pumps (20), depletion of glutathione (21), and damage to DNA (22-25) with subsequent activation of poly(ADP-ribose) synthetase and concomitant cellular energy depletion (25)(26)(27).Under certain conditions, NO produced by each of the three major isoforms of NOS can react with superoxide to form peroxynitrite. The constitutive, endothelial NOS isoform mainly serves physiological functions and is necessary for maintaining normal vascular functions, but under conditions of hypoxia/ reoxygenation and ischemia/reperfusion injury and in atherosclerosis, peroxynitrite formed from endothelial NOS-derived NO can initiate cytotoxic processes (28 -33). Similarly, during neuroinjury in response ...

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“…4). As previously reported (22)(23)(24)(25)(26)(27), peroxynitrite caused a marked increase in DNA single strand breakage in the J774 cells (Fig. 5).…”

Section: Fig 1 Effect Of Meg Ged S-methyl-meg and Aminoguanidinesupporting

confidence: 88%

mentioning

confidence: 99%

Mercaptoethylguanidine and Guanidine Inhibitors of Nitric-oxide Synthase React with Peroxynitrite and Protect against Peroxynitrite-induced Oxidative Damage

Szabó

Ferrer-Sueta

Zingarelli

et al. 1997

Journal of Biological Chemistry

160

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“…Since peroxynitrite is a relatively stable compound (the half-life is about one second at physiological pH [5]), it could penetrate the nucleus, where it might induce damage in DNA. It has been reported that peroxynitrite induces strand breaks in plasmid DNA [18] and oxidative damage in isolated DNA in vitro [19]. We recently found that guanine reacts rapidly with peroxynitrite under physiological conditions to form several substances, two of which are yellow [20].…”

Section: Introductionmentioning

confidence: 98%

Formation of 8‐nitroguanine in DNA treated with peroxynitrite in vitro and its rapid removal from DNA by depurination

1995

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Peroxynitrite is a strong oxidant formed by reaction of nitric oxide with superoxide in inflamed tissues. We have demonstrated that 8-nitroguanine is formed dose-dependently in calf thymus DNA incubated with low concentrations of peroxynitrite in vitro. 8-Nitroguanine in acid-hydrolyzed DNA was chemically reduced into 8-aminoguanine, which was analyzed using high performance liquid chromatography with electrochemical detection. Only peroxynitrite, but not nitrite, tetranitromethane nor NO-releasing compounds, formed 8-nitroguanine. Antioxidants and desferrioxamine inhibited the reaction. 8-Nitroguanine was depurinated from DNA incubated at pH 7.4, 37°C (tu2 = -4 h). Peroxynitrite did not increase 8-oxoguanine levels in DNA.

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“…Peroxynitrite (ONOO-) is formed rapidly by the interaction between NO" and O~-with a rate constant of 6.7× 109 M-l.s -1 in aqueous solution at pH 7.4 [3]. Many workers have demonstrated that ONOO-is an extremely reactive species which readily oxidises various biomolecules, such as low density lipoprotein [4], DNA [5] and ct-l-proteinase inhibitor [6]. In the latter case, the oxidation of ct-1-proteinase inhibitor causes inactivation of its proteinase inhibitory capacity.…”

Section: Introductionmentioning

confidence: 99%

Inactivation of tissue inhibitor of metalloproteinase‐1 by peroxynitrite

Frears¹,

Zhang²,

Blake³

et al. 1996

FEBS Letters

161

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Peroxynitrite (ONOO-) has recently been implicated in connective tissue destruction in vivo. We have studied the effect of ONOO-on the activity of tissue inhibitor of metalloprotelnase-1 (TIMP-1) in vitro. The inactivation of TIMP-1 by ONOO-was dose dependent with 50 ~tM ONOOreducing the inhibitory activity of TIMP-1 towards gelatiuase-A by 50%. High concentrations of ONOO-(500 ~tM-5 mM) caused protein fragmentation whilst lower concentrations (< 250 ~tM) inactivated TIMP-1 without altering the molecular weight. Inactivation could be blocked by ONOO scavengers but not by hydroxyl radical scavengers. Our results show that ONOO-is capable of inactivating TIMP-1, a process which could potentiate metalloproteinase-mediated tissue breakdown.

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A stable solid that generates hydroxyl radical upon dissolution in aqueous solutions: reaction with proteins and nucleic acid

Cited by 236 publications

References 0 publications

Mercaptoethylguanidine and Guanidine Inhibitors of Nitric-oxide Synthase React with Peroxynitrite and Protect against Peroxynitrite-induced Oxidative Damage

Mercaptoethylguanidine and Guanidine Inhibitors of Nitric-oxide Synthase React with Peroxynitrite and Protect against Peroxynitrite-induced Oxidative Damage

Formation of 8‐nitroguanine in DNA treated with peroxynitrite in vitro and its rapid removal from DNA by depurination

Inactivation of tissue inhibitor of metalloproteinase‐1 by peroxynitrite

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