Nitric Oxide Regulation of Tissue Free Radical Injury

Rubbo, Homero; Darley‐Usmar, Victor; Freeman, Bruce Α.

doi:10.1021/tx960037q

Cited by 271 publications

(175 citation statements)

References 123 publications

Supporting

Mentioning

169

Contrasting

Unclassified

Order By: Relevance

“…However, high steadystate levels of ⅐ NO function critically in modulating inflammatory, infectious, and degenerative diseases (2)(3)(4)(5)(6). The reaction of ⅐ NO with metalloproteins can abrogate the function of proteins (7,8).…”

Section: Ptiosmentioning

confidence: 99%

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

Goldstein

Russo

Samuni

2003

Journal of Biological Chemistry

190

124

View full text Add to dashboard Cite

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...

show abstract

Section: Ptiosmentioning

confidence: 99%

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

Goldstein

Russo

Samuni

2003

Journal of Biological Chemistry

190

124

View full text Add to dashboard Cite

show abstract

“…Thus, the formation of RS-NO not only serves biological functions (endogenous storage and transport of NO) but also preserves the antioxidant effect of NO (NO is protected from reaction with superoxide, O 2 . , which would lead to formation of a potent cytotoxic peroxynitrite, ONOO Ϫ ) (11,12). Cytoprotective and antioxidant properties of RS-NO were recently confirmed in studies in vitro and in vivo (13)(14)(15)(16).…”

mentioning

confidence: 94%

Nitrosothiol Formation Catalyzed by Ceruloplasmin

Inoue¹,

Akaike²,

Miyamoto³

et al. 1999

Journal of Biological Chemistry

187

View full text Add to dashboard Cite

Ceruloplasmin (CP) is a major multicopper-containing plasma protein that is not only involved in iron metabolism through its ferroxidase activity but also functions as an antioxidant. However, physiological substrates for CP have not been fully identified nor has the role of CP been fully understood. The reaction of nitric oxide (NO) with CP was investigated in view of nitrosothiol (RS-NO) formation. First, formation of heavy metal-or CP-catalyzed RS-NO was examined with physiologically relevant concentrations of NO and various thiol compounds (RSH) such as glutathione (GSH). Among the various heavy metal ions and copper-containing enzymes and proteins examined, only copper ion (Cu 2؉ ) and CP showed potent RS-NO (S-nitrosoglutathione)-producing activity. Also, RS-NO-forming catalytic activity was evident for CP added exogenously to RAW264 cells expressing inducible NO synthase in culture, but this was not the case for copper ion. Similarly, CP produced endogenously by HepG2 cells showed potent RS-NO-forming activity in the cell culture. One-electron oxidation of NO appears to be operative for RS-NO production via electron transfer from type 1 copper to a cluster of types 2 and 3 copper in CP. Neurological disorders are associated with aceruloplasminemia; besides RS-NO, S-nitrosoglutathione particularly has been shown to have neuroprotective effect against oxidative stress induced by iron overload. Thus, we suggest that CP plays an important catalytic role in RS-NO formation, which may contribute to its potent antioxidant and cytoprotective activities in vivo in mammalian biological systems.

show abstract

“…NO modulates oxidative and free radical reactions, inflammatory cell function, posttranslational protein modification, neurotransmission, and regulation of gene expression (2)(3)(4)(5).…”

mentioning

confidence: 99%

Red cell membrane and plasma linoleic acid nitration products: Synthesis, clinical identification, and quantitation

Baker

Schöpfer

Sweeney

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

192

191

View full text Add to dashboard Cite

Nitric oxide ( • NO) and its reactive metabolites mediate the oxidation, nitration, and nitrosation of DNA bases, amino acids, and lipids. Here, we report the structural characterization and quantitation of two allylic nitro derivatives of linoleic acid (LNO 2), present as both free and esterified species in human red cell membranes and plasma lipids. The LNO 2 isomers 10-nitro-9-cis,12-cis-octadecadienoic acid and 12-nitro-9-cis,12-cis-octadecadienoic acid were synthesized and compared with red cell and plasma LNO 2 species based on chromatographic elution and mass spectral properties. Collision-induced dissociation fragmentation patterns from synthetic LNO 2 isomers were identical to those of the two most prevalent LNO 2 positional isomers found in red cells and plasma. By using • NO exerts a particularly broad influence on oxidative inflammatory reactions by reacting at diffusion-limited rates with superoxide ( • O 2 Ϫ , k ϭ 1.9 ϫ 10 10 M Ϫ1 ⅐sec Ϫ1 ) to yield peroxynitrite (ONOO Ϫ ) and its conjugate acid, peroxynitritrous acid (ONOOH), the latter of which undergoes homolytic scission to nitrogen dioxide ( • NO 2 ) and hydroxyl radical ( • OH) (2, 6). Also, biological conditions favor the reaction of ONOO Ϫ with CO 2 , generating nitrosoperoxycarbonate (ONO-OCO 2 Ϫ ; k ϭ 3 ϫ 10 4 M Ϫ1 ⅐sec Ϫ1 ), which yields • NO 2 and carbonate ( • CO 3 Ϫ ) radicals by means of homolysis or rearranges to NO 3 Ϫ and CO 2 (7). During inflammation, neutrophil myeloperoxidase and heme proteins, such as myoglobin and cytochrome c, form H 2 O 2 -dependent Compound I intermediates that are direct oxidants and catalyze the consumption of • NO and the oxidation of nitrite (NO 2 Ϫ ) to • NO 2 (8-11). Although the rate of reaction of • NO with O 2 is slow (k ϭ 2 ϫ 10 6 M Ϫ2 ⅐sec Ϫ1 ), the small molecular radius, uncharged nature, and lipophilicity of • NO and O 2 facilitate their diffusion and concentration in membranes and lipoproteins up to 20-fold (12-14). This ''molecular lens'' effect that is induced by solvation in hydrophobic cell compartments accelerates the reaction of • NO with O 2 to yield N 2 O 3 and N 2 O 4 . As a consequence of this diversity of • NO reactions with partially reduced oxygen species, a rich spectrum of products is formed that orchestrates target molecule oxidation, nitrosation, and nitration reactions.Multiple mechanisms account for the nitration of fatty acids by• NO-derived species (15)(16)(17)(18)(19)(20). During both basal cell-signaling and tissue-inflammatory conditions, • NO 2 that is generated by the aforementioned reactions can react with membrane and lipoprotein lipids. Environmental sources also yield • NO 2 as a product of combustion.• NO 2 initiates autooxidation of polyunsaturated fatty acids by means of hydrogen abstraction from the bis-allylic carbon, to form nitrous acid and a resonance-stabilized allylic radical (21). This lipid radical species predominantly reacts with molecular oxygen to form a peroxyl radical. During the unique oxidationreduction conditions of inflammation or ischemia-...

show abstract

Nitric Oxide Regulation of Tissue Free Radical Injury

Cited by 271 publications

References 123 publications

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

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

Nitrosothiol Formation Catalyzed by Ceruloplasmin

Red cell membrane and plasma linoleic acid nitration products: Synthesis, clinical identification, and quantitation

Contact Info

Product

Resources

About