Spin Trapping of Nitric Oxide by Nitronylnitroxides: Measurement of the Activity of NO Synthase from Rat Cerebellum

Woldman, Yakov Y.; Khramtsov, Valery V.; Grigor'ev, I. A.; Kiriljuk, I. A.; Utepbergenov, Darkhan

doi:10.1006/bbrc.1994.1912

Cited by 65 publications

(52 citation statements)

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“…8 and are summarized in Table I. These values agree with those determined previously by stopped-flow EPR and spectrophotometric methods (12,14) and are somewhat lower than that determined using hemoglobin as a competing agent (16). The literature data also are summarized in Table I.…”

Section: Reactions Of Ptio and Carboxy-ptio With ⅐ No ⅐ No 2 And Osupporting

confidence: 83%

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Reactions of PTIO and Carboxy-PTIO with ·NO, ·NO2, andO2.¯

Goldstein

Russo

Samuni

2003

Journal of Biological Chemistry

186

124

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Nitronyl nitroxides, such as derivatives of 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl 3-oxide (PTIOs), react with ⅐ NO to form the corresponding imino nitroxides (PTIs) and ⅐ NO 2 . PTIOs are considered as monitors of ⅐ NO, stoichiometric sources of ⅐ NO 2 , biochemical and physiological effectors, specific tools for the elimination of ⅐ NO, and potential therapeutic agents. However, a better understanding of the chemical properties of PTIOs, especially following their reaction with ⅐ NO, is necessary to resolve many of the reported discrepancies surrounding the effects of PTIOs and to better characterize their potential therapeutic activity. We have generated electrochemically the oxidized and reduced forms of PTIO and carboxy-PTIO (C-PTIO), characterized their absorption spectra, and determined the reduction potentials for the oxoammonium/nitroxide and nitroxide/hydroxylamine couples. The rate constants for the reaction of ⅐ NO 2 with PTIO and C-PTIO to form the corresponding oxoammonium cations (PTIO ؉ s) and nitrite were determined to be (1. Nitric oxide ( ⅐ NO) 1 is synthesized by ⅐ NO synthase from the substrate L-arginine in a wide variety of cell types and is a major participant in numerous beneficial physiological functions such as blood pressure regulation, inhibition of platelet aggregation, and neurotransmission (1). However, high steadystate levels of ⅐ NO function critically in modulating inflammatory, infectious, and degenerative diseases (2-6). The reaction of ⅐ NO with metalloproteins can abrogate the function of proteins (7, 8). Moreover, the reactions of ⅐ NO with oxygen and superoxide convert ⅐ NO into other reactive nitrogen species such as ONOO Ϫ , ⅐ NO 2 , or N 2 O 3 , which can react with virtually all of the classes of biomolecules including amino acids, lipids, DNA, thiols, and metals (5, 6, 9 -11). One therapeutic approach to ameliorate ⅐ NO-induced biological damage is to use ⅐ NO scavengers, preferably selective scavengers that distinguish between free ⅐ NO and species exhibiting ⅐ NO-like biological activity.The use of nitronyl nitroxides, such as 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl 3-oxide (PTIO), as selective traps for ⅐ NO is rapidly increasing as reflected by the numerous publications in the recent biomedical literature. PTIO and its derivatives were shown to react with ⅐ NO to form the corresponding imino nitroxides and ⅐ NO 2 (12-16), where k 1 ϭ (0.5 Ϫ 16) ϫ 10 4 M Ϫ1 s Ϫ1 (Reaction 1) (12, 14, 16).Both the nitronyl nitroxide and the imino nitroxide are detectable and distinguishable by EPR spectroscopy, and various PTIOs are used as spin traps for ⅐ NO (13, 14, 16 -18). In addition, Akaike et al. (12) demonstrated that excess of ⅐ NO 2 had no effect on the EPR spectrum of PTIOs and, subsequently, Reaction 1 has been adopted to generate ⅐ NO 2 (19,20). Likewise, direct scavenging of ⅐ NO by PTIOs has been shown to inhibit endothelium-derived relaxing factor (EDRF) in bioassay in vitro (12), to cause cell cycle alteration, to result in oxidative stress and a...

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Section: Reactions Of Ptio and Carboxy-ptio With ⅐ No ⅐ No 2 And Osupporting

confidence: 83%

“…PTIO and its derivatives were shown to react with ⅐ NO to form the corresponding imino nitroxides and ⅐ NO 2 (12)(13)(14)(15)(16), where k 1 ϭ (0.5 Ϫ 16) ϫ 10 4 M Ϫ1 s Ϫ1 (Reaction 1) (12,14,16).…”

Section: Ptiosmentioning

confidence: 99%

Reactions of PTIO and Carboxy-PTIO with ·NO, ·NO2, andO2.¯

Goldstein

Russo

Samuni

2003

Journal of Biological Chemistry

186

124

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“…Imino nitroxyl radicals (Ullman & Osiecki, 1970) were apparently the first reported stable NRs with spectral sensitivity in physiological range but did not find applications as pH probes due to the complexity of their EPR spectra and rapid reduction to EPR silent products in biological fluids (Woldman et al, 1994;Haseloff et al, 1997;. The observed pH effects on the NRs of piperidine and pyrrolidine types with ionizable functional groups were impractically small (Hsia & Boggs, 1972;Quintanilha & Mehlhorn, 1978;Nakaie et al, 1981;Mathew & Dodd, 1985;Khramtsov & Weiner, 1988;Saracino et al, 2002) due to the long distance between radical center and ionizable group.…”

Section: Ph Effect On the Epr Spectra Of Stable Nitroxidesmentioning

confidence: 99%

“…Application of simple lowmolecular weight nitronyl nitroxides (NNRs) as NO-sensitive probes seems to be very attractive. The scavenging of nitric oxide by NNRs has been used for NO detection by EPR spectroscopy and to antagonize biological actions of nitric oxide (Akaike et al, 1993;Joseph et al, 1993;Woldman et al, 1994;Blasig et al, 2002;Cao & Reith, 2002). The detection of NO using NNR is based on the specific radical-radical reaction (see Fig.16a) followed by EPRmeasured spectra changes.…”

Section: In Vivo Assessment Of Nitric Oxide Using Nitronyl Nitroxidesmentioning

confidence: 99%

“…Half a century of continuous progress in nitroxide chemistry has resulted in the design of specific NRs for spin labeling (Berliner, 1998), sitedirected spin labeling (Hubbell et al, 2000), EPR oximetry (Halpern et al, 1994;Swartz, 2004), pH (Khramtsov et al, 1982, thiols (Khramtsov et al, 1989(Khramtsov et al, , 1997, redox (Swartz et al, 2007) and NO measurements (Akaike et al, 1993;Joseph et al, 1993;Woldman et al, 1994). Over the past decade low-field L-band (1.2 GHz) EPR spectrometers and imagers have become commercially available allowing for functional EPR measurements in isolated organs (Komarov et al, 2012) and small animals such as mice Bobko et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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