Oxidation of nitrogen oxides by bound dioxygen in hemoproteins

During the past several years, major advances have been made in understanding how reactive oxygen species (ROS) and nitrogen species (RNS) participate in signal transduction. Identification of the specific targets and the chemical reactions involved still remains to be resolved with many of the signaling pathways in which the involvement of reactive species has been determined. Our understanding is that ROS and RNS have second messenger roles. While cysteine residues in the thiolate (ionized) form found in several classes of signaling proteins can be specific targets for reaction with H 2 O 2 and RNS, better understanding of the chemistry, particularly kinetics, suggests that for many signaling events in which ROS and RNS participate, enzymatic catalysis is more likely to be involved than non-enzymatic reaction. Due to increased interest in how oxidation products, particularly lipid peroxidation products, also are involved with signaling, a review of signaling by 4-hydroxy-2-nonenal (HNE) is included. This article focuses on the chemistry of signaling by ROS, RNS, and HNE and will describe reactions with selected target proteins as representatives of the mechanisms rather attempt to comprehensively review the many signaling pathways in which the reactive species are involved. Keywords signaling; glutathione; thioredoxin; oxidants; reactive oxygen species; thiols; peroxide; nitric oxide; peroxynitrite; 4-hydroxynonenal; cysteine; hydrogen peroxide; protein tyrosine phosphatase; reactive nitrogen species; eNOS; iNOS; nNOS; soluble guanylate cyclase; cGMP; tyrosine nitration; fatty acid nitration; NO-heme; NO-metal complexes; nitrite; protein kinase C; ERK; JNK; p38MAPK; tyrosine kinase receptors; calcium OVERVIEW OF SIGNALING BY REACTIVE SPECIESUnderstanding of the roles of reactive oxygen species (ROS), reactive nitrogen species (RNS) and the lipid peroxidation product, 4-hydroxy-2-nonenal (HNE) in signaling has evolved rapidly during the last decade. This has been markedly helped by identification of the specific targets in signaling pathways. In previous reviews, we defined how ROS, H 2 O 2 in particular,

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“…NOSderived · NO is rapidly converted to nitrate by oxyhemoglobin or oxymyoglobin (Reaction <23>) (140).…”

Section: Nitrite Signalingmentioning

confidence: 99%

“…It was determined that the concentration of xanthine oxidase and nitrite were sufficient in no-flow ischemic cardiac tissue to generate · NO levels comparable to NOS (158). Doyle and coworkers (140) were the first to describe nitrite reductase activity by deoxyhemoglobin (Reaction <32>).…”

Section: <31>mentioning

confidence: 99%

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

Forman

Fukuto

Miller

et al. 2008

Archives of Biochemistry and Biophysics

217

165

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“…Ordinary differential equations (Eqns. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] describe the mass actions of chemical species. For the interaction of HbFe II CO and RBCs (Box 1), reactions in both the phase inside of RBCs and the extracellular solution were considered.…”

Section: Kinetic Simulation Of Hbfe II Co/hbfe Ii No Reaction With Rbcsmentioning

confidence: 99%

“…As a first approximation, NO that diffuses into the lumen of the blood vessel is expected to react rapidly (∼10 7 M -1 sec -1 ) with oxyhemoglobin (HbFe II O 2 ) [5,6,7] to form methemoglobin (metHbFe III ) and nitrate. It is therefore necessary to preserve NO bioactivity in the proximity of a pool of hemoglobin (∼10 mM) in the lumen.…”

Section: Introductionmentioning

confidence: 99%

“…It is therefore necessary to preserve NO bioactivity in the proximity of a pool of hemoglobin (∼10 mM) in the lumen. Several solutions to this paradox have been proposed, including i) the diffusion and transport limitation arises from the encapsulation of hemoglobin (Hb) in erythrocyte [8,9,10,11,12,13,14,5,15,16,17,18], ii) the formation of S-nitroso-hemoglobin (SNO-Hb) from the intramolecular transfer of nitrosylhemoglobin (HbFe II NO) [19,20,21,22,23,24,5,25], and iii) the NO bioactivity transduced from nitrite [26,27,28,29]. In the latter two cases, the formation of HbFe II NO can be argued to play a role for preserving NO bioactivity.…”

Section: Introductionmentioning

confidence: 99%

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Interactions of nitrosylhemoglobin and carboxyhemoglobin with erythrocyte

2008

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Nitrosylhemoglobin (HbFe II NO) has been detected in vivo, and its role in NO transport and preservation has been discussed. To gain insight into the potential role of HbFe II NO, we performed in vitro experiments to determine the effect of oxygenated red blood cells (RBCs) on the dissociation of cell-free HbFe II NO, using carboxyhemoglobin (HbFe II CO) as a comparison. Results show that the apparent half-life of the cell-free HbFe II CO was reduced significantly in the presence of RBCs at 1 % hematocrit. In contrast, RBC did not change the apparent half-life of extracellular HbFe II NO, but caused a shift in the HbFe II NO dissociation product from methemoglobin (metHbFe III ) to oxyhemoglobin (HbFe II O 2 ). Extracellular hemoglobin was able to extract CO from HbFe II COcontaining RBC, but not NO from HbFe II NO-containing RBC. Although these results appear to suggest some unusual interactions between HbFe II NO and RBC, the data are explainable by simple HbFe II NO dissociation and hemoglobin oxidation with known rate constants. A kinetic model consisting of these reactions shows that i) deoxyhemoglobin is an intermediate in the reaction of HbFe II NO oxidation to metHbFe III , ii) the rate-limiting step of HbFe II NO decay is the dissociation of NO from HbFe II NO, iii) the magnitude of NO diffusion rate constant into RBC is estimated to be ∼10 4 M -1 s -1 , consistent with previous results determined from a competition assay, and iv) no additional chemical reactions are required to explain these data.

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Pathogenesis and Treatment of the Adult Respiratory Distress Syndrome

et al. 1996

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The adult respiratory distress syndrome is an acute clinical illness characterized by noncardiogenic pulmonary edema and refractory hypoxemia. Injury to the alveolar-capillary barrier and lung inflammation lead to intrapulmonary shunting of blood, surfactant depletion, and pulmonary vascular obstruction. Numerous mediators contribute to the pathologic response. Conventional therapy includes treating underlying causes and positive pressure mechanical ventilation. Concern about pressure-induced lung injury had led to new strategies to accomplish adequate gas exchange. Novel therapeutic interventions have included extracorporeal support techniques, use of compounds designed to neutralize proinflammatory cytokines, and administration of surfactants, but these efforts have not definitely affected mortality in randomized trials. Potent antioxidant agents have shown promise in animal models of acute lung injury, but human studies are lacking. Inhaled nitric oxide appears to have temporary effects on pulmonary artery pressure and on ventilation or perfusion relationships, but longer-term efficacy and safety in patients suffering from adult respiratory distress syndrome is unknown and awaits results of ongoing clinical trials.

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Oxidation of nitrogen oxides by bound dioxygen in hemoproteins

Cited by 588 publications

References 23 publications

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

Interactions of nitrosylhemoglobin and carboxyhemoglobin with erythrocyte

Pathogenesis and Treatment of the Adult Respiratory Distress Syndrome

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