Ascorbate Is a Potent Antioxidant against Peroxynitrite-induced Oxidation Reactions

Self Cite

Section: Resultsmentioning

confidence: 99%

“…Experimental Conditions-Because nitrosation reactions are sensitive to the presence of metal ions, the buffer solutions were exposed to a chelating resin (Chelex 100) as described previously (12).…”

Section: Chemicals-n-acetyltryptophanmentioning

confidence: 99%

Formation of S-Nitrosothiols from Regiospecific Reaction of Thiols with N-Nitrosotryptophan Derivatives

Sonnenschein¹,

Groot

Kirsch

2004

Self Cite

“…Moreover, ascorbate reacts faster with CO 3 . than GSH (65).Consequently, in aqueous environments, ascorbate may be more important than GSH in counteracting the oxidant action of free radicals. This has been shown to occur in the case of the acetaminophen-derived radical (50) and more recently, in the case of peroxynitritederived radicals (65).…”

Section: Fig 2 Effects Of Hco 3 ؊ /Co 2 On Oxygen Consumption Durinmentioning

confidence: 99%

Carbon Dioxide Stimulates the Production of Thiyl, Sulfinyl, and Disulfide Radical Anion from Thiol Oxidation by Peroxynitrite

Bonini

Augusto

2001

173

105

Reaction of peroxynitrite with the biological ubiquitous CO 2 produces about 35% yields of two relatively strong one-electron oxidants, CO 3 . and ⅐ NO 2 , but the remaining of peroxynitrite is isomerized to the innocuous nitrate. Partial oxidant deactivation may confound interpretation of the effects of HCO 3 ؊ /CO 2 on the oxidation of targets that react with peroxynitrite by both one-and two-electron mechanisms. Thiols are example of such targets, and previous studies have reported that HCO 3 ؊ / CO 2 partially inhibits GSH oxidation by peroxynitrite at pH 7.4. To differentiate the effects of HCO 3 ؊ /CO 2 on twoand one-electron thiol oxidation, we monitored GSH, cysteine, and albumin oxidation by peroxynitrite at pH 5.4 and 7.4 by thiol disappearance, oxygen consumption, fast flow EPR, and EPR spin trapping. Our results demonstrate that HCO 3 ؊ /CO 2 diverts thiol oxidation by peroxynitrite from two-to one-electron mechanisms particularly at neutral pH. At acid pH values, thiol oxidation to free radicals predominates even in the absence of HCO 3 ؊ /CO 2 . In addition to the previously characterized thiyl radicals (RS ⅐ ), we also characterized radicals derived from them such as the corresponding sulfinyl (RSO ⅐ ) and disulfide anion radical (RSSR ⅐ ؊ ) of both GSH and cysteine. Thiyl, RSO ⅐ and RSSR ⅐ ؊ are reactive radicals that may contribute to the biodamaging and bioregulatory actions of peroxynitrite.Peroxynitrite 1 (ONOO Ϫ ϩ ONOOH), which is formed by the fast reaction between ⅐ NO and O 2 . , has been receiving increasing attention as a mediator of human diseases and as a toxin against invading microorganisms (1-5). The compound is a potent oxidant that is able to oxidize and nitrate a variety of biological targets by mechanisms that are presently being elucidated (6 -16). In general terms, peroxynitrite-mediated oxidations are either bimolecular, first order on peroxynitrite and biomolecule concentration, or unimolecular, first order on peroxynitrite and independent of biomolecule concentration. Bimolecular processes can result in product yield either around stoichiometry and over, as is the case for thiol oxidation (17), or around 35% , as is the case for carbon dioxide (CO 2 ) oxidation (10, 14 -16). Presently, most investigators accept that product yields around 30% are characteristic of peroxynitrite-mediated free radical processes. Indeed, it has been established that ONOO Ϫ protonation (pK a ϭ 6.6) leads to its fast decomposition (k ϭ 0.17 s Ϫ1 at pH 7.4) to yield approximately 70% nitrate and 30% hydroxyl radical ( ⅐ OH) and nitrogen dioxide ( ⅐ NO 2 ) (Fig. 1, path 1) (7)(8)(9)(11)(12)(13)(14). These radicals are the species responsible for peroxynitrite-mediated unimolecular oxidations. In the presence of HCO 3 Ϫ , ONOO Ϫ decomposes much faster because of its reaction with CO 2 (k ϭ 2.6 ϫ 10 4 M Ϫ1 s Ϫ1 at pH 7.4, 25°C) (18, 19) to produce approximately 65% nitrate and 35% carbonate radical anion (CO 3 . ) and ⅐ NO 2 (Fig. 1, path 2) (10, 14 -16).The fast rate constant of this reaction and...

“…Experimental Conditions-Because nitrosation reactions are sensitive to the presence of metal ions, solutions were exposed to chelating resin (Chelex 100) as described previously (27).…”

Section: Methodsmentioning

confidence: 99%

Regiospecific Nitrosation of N-terminal-blocked Tryptophan Derivatives by N2O3 at Physiological pH

Kirsch¹,

Fuchs²,

Groot

2003

Self Cite

Nitric oxide ( ⅐ NO) is involved in a great variety of physiological and pathophysiological processes, including the regulation of vascular tonus, immune response, and neurotransmission (1). In mammals the basal level of ⅐ NO (in the aqueous phase) is in the nanomolar range (2). However, the local ⅐ NO concentrations can be increased substantially in areas with high NO synthase activity and/or in hydrophobic regions (3, 4), thereby facilitating the formation of dinitrogen trioxide (N 2 O 3 ) (Equations 1 (5) and 2 (6)).2 ⅐ NO ϩ O 2 3 2 ⅐ NO 2 k 1 ϭ 2.9 ϫ 10 6 M Ϫ2 s Ϫ1