RESUMO

Macrophages play a pivotal role in the early stages of atherosclerosis development; they excessively accumulate cholesterol in the cytosol in response to modified Low Density Lipoprotein (mLDL). The mLDL are incorporated through scavenger receptors. CD36 is a high-affinity cell surface scavenger receptor that facilitates the binding and uptake of long-chain fatty acids and mLDL into the cell. Numerous structurally diverse ligands can initiate signaling responses through CD36 to regulate cell metabolism, migration, and angiogenesis. Nitro-fatty acids are endogenous electrophilic lipid mediators that react with and modulate the function of multiple enzymes and transcriptional regulatory proteins. These actions induce the expression of several anti-inflammatory and cytoprotective genes and limit pathologic responses in experimental models of atherosclerosis, cardiac ischemia/reperfusion, and inflammatory diseases. Pharmacological and genetic approaches were used to explore the actions of nitro-oleic acid (NO2-OA) on macrophage lipid metabolism. Pure synthetic NO2-OA dose-dependently increased CD36 expression in RAW264.7 macrophages and this up-regulation was abrogated in BMDM from Nrf2-KO mice. Ligand binding analysis revealed that NO2-OA specifically interacts with CD36, thus limiting the binding and uptake of mLDL. Docking analysis shows that NO2-OA establishes a low binding energy interaction with the alpha helix containing Lys164 in CD36. NO2-OA also restored autophagy flux in mLDL-loaded macrophages, thus reversing cholesterol deposition within the cell. In aggregate, these results indicate that NO2-OA reduces cholesterol uptake by binding to CD36 and increases cholesterol efflux by restoring autophagy.

Assuntos

Antígenos CD36 , Ácido Oleico , Animais , Antígenos CD36/genética , Colesterol , Células Espumosas/metabolismo , Ligantes , Lipoproteínas LDL/metabolismo , Macrófagos/metabolismo , Camundongos

RESUMO

Inflammation plays a major role in the onset and development of chronic non-communicable diseases like obesity, cardiovascular diseases and cancer. Combined, these diseases represent the most common causes of death worldwide, thus development of novel pharmacological approaches is crucial. Electrophilic nitroalkenes derived from fatty acids are formed endogenously and exert anti-inflammatory actions by the modification of proteins involved in inflammation signaling cascades. We have developed novel nitroalkenes derived from α-tocopherol aiming to increase its salutary actions by adding anti-inflammatory properties to a well-known nutraceutical. We synthesized and characterized an α-tocopherol-nitroalkene (NATOH) and two hydrosoluble analogues derived from Trolox (NATxME and NATx0). We analyzed the kinetics of the Michael addition reaction of these compounds with thiols in micellar systems aiming to understand the effect of hydrophobic partition on the reactivity of nitroalkenes. We studied NATxME in vitro showing it exerts non-conventional anti-inflammatory responses by inducing Nrf2-Keap1-dependent gene expression and inhibiting the secretion of NF-κB dependent pro-inflammatory cytokines. NATxME was also effective in vivo, inhibiting neutrophil recruitment in a zebrafish model of inflammation. This work lays the foundation for the rational design of a new therapeutic strategy for the prevention and treatment of metabolic and inflammation-related diseases.

Assuntos

Alcenos/síntese química , Alcenos/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Transdução de Sinais , Tocoferóis/síntese química , Tocoferóis/farmacologia , Alcenos/química , Animais , Anti-Inflamatórios/química , Cromanos/síntese química , Cromanos/química , Cromanos/farmacologia , Cinética , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Micelas , Infiltração de Neutrófilos/efeitos dos fármacos , Células RAW 264.7 , Tocoferóis/química , Peixe-Zebra

RESUMO

Nitro-fatty acids (NO2-FA) are electrophilic signaling mediators formed in tissues during inflammation, which are able to induce pleiotropic cytoprotective and antioxidant pathways including up regulation of Nuclear factor erythroid 2-related factor 2 (Nrf2) responsive genes. Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons associated to an inflammatory process that usually aggravates the disease progression. In ALS animal models, the activation of the transcription factor Nrf2 in astrocytes confers protection to neighboring neurons. It is currently unknown whether NO2-FA can exert protective activity in ALS through Nrf2 activation. Herein we demonstrate that nitro-arachidonic acid (NO2-AA) or nitro-oleic acid (NO2-OA) administrated to astrocytes expressing the ALS-linked hSOD1(G93A) induce antioxidant phase II enzyme expression through Nrf2 activation concomitant with increasing intracellular glutathione levels. Furthermore, treatment of hSOD1(G93A)-expressing astrocytes with NO2-FA prevented their toxicity to motor neurons. Transfection of siRNA targeted to Nrf2 mRNA supported the involvement of Nrf2 activation in NO2-FA-mediated protective effects. Our results show for the first time that NO2-FA induce a potent Nrf2-dependent antioxidant response in astrocytes capable of preventing motor neurons death in a culture model of ALS.

Assuntos

Esclerose Lateral Amiotrófica/metabolismo , Antioxidantes/metabolismo , Astrócitos/metabolismo , Neurônios Motores/metabolismo , Fator 2 Relacionado a NF-E2/genética , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Animais , Antioxidantes/química , Ácido Araquidônico/química , Ácido Araquidônico/metabolismo , Astrócitos/patologia , Modelos Animais de Doenças , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Glutationa/biossíntese , Humanos , Camundongos , Neurônios Motores/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico/química , Ácido Oleico/química , Ácido Oleico/metabolismo , Transdução de Sinais/genética , Superóxido Dismutase/metabolismo , Ativação Transcricional/genética

RESUMO

Human serum albumin (HSA) is the most abundant protein in plasma. Cys34, the only free Cys residue, is the predominant plasma thiol and a relevant sacrificial antioxidant. Both in vivo circulating HSA and pharmaceutical preparations are heterogeneous with respect to the oxidation state of Cys34. In this work, we developed an external pH gradient chromatofocusing procedure that allows the analysis of the oxidation status of HSA in human plasma and biopharmaceutical products based on the different apparent isoelectric points and chemical properties of the redox isoforms. Specifically, reduced-mercury blocked HSA (HSA-SHg(+)), HSA with Cys34 oxidized to sulfenic acid (HSA-SOH) and HSA oxidized to sulfinate anion (HSA-SO2(-)) can be separated with resolutions of 1.4 and 3.1 (first and last pair) and hence quantified and purified. In addition, an N-terminally degraded isoform (HSA3-585) in different redox states can be resolved as well. Confirmation of the identity of the chromatofocusing isolated isoforms was achieved by high resolution whole protein MS. It is proposed that the chromatofocusing procedure can be used to produce more exact and complete descriptions of the redox status of HSA in vivo and in vitro. Finally, the scalability capabilities of the chromatofocusing procedure allow for the preparation of highly pure standards of several redox isoforms of HSA.

Assuntos

Cromatografia Líquida de Alta Pressão/métodos , Albumina Sérica/química , Albumina Sérica/isolamento & purificação , Idoso , Humanos , Concentração de Íons de Hidrogênio , Ponto Isoelétrico , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/análise , Isoformas de Proteínas/química , Isoformas de Proteínas/isolamento & purificação , Albumina Sérica/análise

RESUMO

PknG from Mycobacterium tuberculosis is a Ser/Thr protein kinase that regulates key metabolic processes within the bacterial cell as well as signaling pathways from the infected host cell. This multidomain protein has a conserved canonical kinase domain with N- and C-terminal flanking regions of unclear functional roles. The N-terminus harbors a rubredoxin-like domain (Rbx), a bacterial protein module characterized by an iron ion coordinated by four cysteine residues. Disruption of the Rbx-metal binding site by simultaneous mutations of all the key cysteine residues significantly impairs PknG activity. This encouraged us to evaluate the effect of a nitro-fatty acid (9- and 10-nitro-octadeca-9-cis-enoic acid; OA-NO2) on PknG activity. Fatty acid nitroalkenes are electrophilic species produced during inflammation and metabolism that react with nucleophilic residues of target proteins (i.e., Cys and His), modulating protein function and subcellular distribution in a reversible manner. Here, we show that OA-NO2 inhibits kinase activity by covalently adducting PknG remote from the catalytic domain. Mass spectrometry-based analysis established that cysteines located at Rbx are the specific targets of the nitroalkene. Cys-nitroalkylation is a Michael addition reaction typically reverted by thiols. However, the reversible OA-NO2-mediated nitroalkylation of the kinase results in an irreversible inhibition of PknG. Cys adduction by OA-NO2 induced iron release from the Rbx domain, revealing a new strategy for the specific inhibition of PknG. These results affirm the relevance of the Rbx domain as a target for PknG inhibition and support that electrophilic lipid reactions of Rbx-Cys may represent a new drug strategy for specific PknG inhibition.

Assuntos

Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Mycobacterium tuberculosis/metabolismo , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/metabolismo , Rubredoxinas/metabolismo , Alcenos/química , Alcenos/metabolismo , Domínio Catalítico/fisiologia , Dicroísmo Circular , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Mutagênese Sítio-Dirigida , Nitrocompostos/química , Nitrocompostos/metabolismo , Rubredoxinas/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz

RESUMO

Nitroalkene derivatives of fatty acids act as adaptive, anti-inflammatory signalling mediators, based on their high-affinity PPARgamma (peroxisome-proliferator-activated receptor gamma) ligand activity and electrophilic reactivity with proteins, including transcription factors. Although free or esterified lipid nitroalkene derivatives have been detected in human plasma and urine, their generation by inflammatory stimuli has not been reported. In the present study, we show increased nitration of cholesteryl-linoleate by activated murine J774.1 macrophages, yielding the mononitrated nitroalkene CLNO2 (cholesteryl-nitrolinoleate). CLNO2 levels were found to increase approximately 20-fold 24 h after macrophage activation with Escherichia coli lipopolysaccharide plus interferon-gamma; this response was concurrent with an increase in the expression of NOS2 (inducible nitric oxide synthase) and was inhibited by the (*)NO (nitric oxide) inhibitor L-NAME (N(G)-nitro-L-arginine methyl ester). Macrophage (J774.1 and bone-marrow-derived cells) inflammatory responses were suppressed when activated in the presence of CLNO2 or LNO2 (nitrolinoleate). This included: (i) inhibition of NOS2 expression and cytokine secretion through PPARgamma and *NO-independent mechanisms; (ii) induction of haem oxygenase-1 expression; and (iii) inhibition of NF-kappaB (nuclear factor kappaB) activation. Overall, these results suggest that lipid nitration occurs as part of the response of macrophages to inflammatory stimuli involving NOS2 induction and that these by-products of nitro-oxidative reactions may act as novel adaptive down-regulators of inflammatory responses.

Assuntos

Ésteres do Colesterol/metabolismo , Ativação de Macrófagos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Animais , Antígenos CD36/metabolismo , Linhagem Celular , Ésteres do Colesterol/síntese química , Ésteres do Colesterol/farmacologia , Ativação Enzimática/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Interferon gama/farmacologia , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Fatores de Necrose Tumoral/metabolismo

RESUMO

Sulfenic acid is formed upon oxidation of thiols and is a central intermediate in the redox modulation of an increasing number of proteins. Methods for quantifying or even detecting sulfenic acid are scarce. Herein, the reagent 7-chloro-4-nitrobenz-2-oxa-1,3-diazole was determined not to be suitable as a chromophoric probe for sulfenic acid in human serum albumin (HSA-SOH) because of lack of specificity. Thionitrobenzoate (TNB) reacted with HSA exposed to hydrogen peroxide, but not control or thiol-blocked HSA. The reaction was biphasic. The first phase was approximately 20-fold faster than the second phase and first order in HSA-SOH and TNB (105 +/- 11 M-1 s-1, 25 degrees C, pH 7.4), allowing quantitative data on HSA-SOH formation and reactivity to be obtained. Exposure of reduced HSA (0.5 mM) to hydrogen peroxide (4 mM, 37 degrees C, 4 min) yielded 0.18 +/- 0.02 mol of HSA-SOH per mol of HSA. HSA-SH reacted with hydrogen peroxide at 2.7 +/- 0.7 M-1 s-1 (37 degrees C, pH 7.4), while HSA-SOH reacted at 0.4 +/- 0.2 M-1 s-1, yielding sulfinic acid (HSA-SO2H), as detected by mass spectrometry. The rate constants of HSA-SOH with targets of analytical interest such as dimedone and sodium arsenite were determined. HSA-SOH did not react appreciably with the plasma reductants ascorbate or urate, nor with free basic amino acids. In contrast, HSA-SOH reacted rapidly with the plasma thiols cysteine, glutathione, homocysteine, and cysteinylglycine at 21.6 +/- 0.2, 2.9 +/- 0.5, 9.3 +/- 0.9, and 55 +/- 3 M-1 s-1 (25 degrees C, pH 7.4), respectively, supporting a role for HSA-SOH in the formation of mixed disulfides.

Assuntos

Albumina Sérica/química , Ácidos Sulfênicos/química , Arsenitos/química , Cicloexanonas/química , Humanos , Peróxido de Hidrogênio/química , Estrutura Molecular , Nitrobenzoatos/química , Oxirredução , Compostos de Sódio/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Compostos de Sulfidrila/química

RESUMO

Human recombinant copper-zinc superoxide dismutase (CuZnSOD) was inactivated by peroxynitrite, the product of the reaction between nitric oxide and superoxide. The concentration of peroxynitrite that decreased the activity by 50% (IC(50)) was approximately 100 microM at 5 microM CuZnSOD and the inactivation was higher at alkaline pH. Stopped-flow determinations showed that the second-order rate constant for the direct reaction of peroxynitrite with CuZnSOD was (9.4 +/- 1.0) x 10(3) M(-1) s(-1) per monomer at pH 7.5 and 37 degrees C. Addition of peroxynitrite (1 mM) to CuZnSOD (0.5 mM) in the presence of the spin trap 2-methyl-2-nitrosopropane led to the electron paramagnetic resonance detection of an anisotropic signal typical of a protein radical adduct. Treatment with Pronase revealed a nearly isotropic signal consistent with the formation of histidinyl radical. The effects of nitrite, hydrogen peroxide, bicarbonate, and mannitol on the inactivation were assessed. Considering the mechanism accepted for the reaction of CuZnSOD with hydrogen peroxide and the fact that CuZnSOD promotes the nitration of phenolics by peroxynitrite, we herein propose that peroxynitrite reacts with CuZnSOD leading to nitrogen dioxide plus a copper-bound hydroxyl radical species that reacts with histidine residues, forming histidinyl radical.

Assuntos

Inibidores Enzimáticos/farmacologia , Histidina/química , Ácido Peroxinitroso/farmacologia , Superóxido Dismutase/antagonistas & inibidores , Bicarbonatos/química , Relação Dose-Resposta a Droga , Espectroscopia de Ressonância de Spin Eletrônica , Radicais Livres , Humanos , Peróxido de Hidrogênio/química , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Cinética , Manitol/química , Modelos Químicos , Nitritos/química , Compostos Nitrosos/química , Ácido Peroxinitroso/química , Proteínas Recombinantes/química , Superóxido Dismutase/química

RESUMO

Previous reports proposed that peroxynitrite (ONOO-) oxidizes alpha-tocopherol (alpha-TOH) through a two-electron concerted mechanism. In contrast, ONOO- oxidizes phenols via free radicals arising from peroxo bond homolysis. To understand the kinetics and mechanism of alpha-TOH and gamma-tocopherol (gamma-TOH) oxidation in low-density lipoprotein (LDL) (direct vs. radical), we exposed LDL to ONOO- added as a bolus or an infusion. Nitric oxide (.NO), ascorbate and CO2 were used as key biologically relevant modulators of ONOO- reactivity. Although approximately 80% alpha-TOH and gamma-TOH depletion occurred within 5 min of incubation of 0.8 microM LDL with a 60 microM bolus of ONOO-, an equimolar infusion of ONOO- over 60 min caused total consumption of both antioxidants. gamma-Tocopherol was preserved relative to alpha-TOH, probably due to gamma-tocopheroxyl radical recycling by alpha-TOH. alpha-TOH oxidation in LDL was first order in ONOO- with approximately 12% of ONOO- maximally available. Physiological concentrations of.NO and ascorbate spared both alpha-TOH and gamma-TOH through independent and additive mechanisms. High concentrations of.NO and ascorbate abolished alpha-TOH and gamma-TOH oxidation. Nitric oxide protection was more efficient for alpha-TOH in LDL than for ascorbate in solution, evidencing the kinetically highly favored reaction of lipid peroxyl radicals with.NO than with alpha-TOH as assessed by computer-assisted simulations. In addition, CO2 (1.2 mM) inhibited both alpha-TOH and lipid oxidation. These results demonstrate that ONOO- induces alpha-TOH oxidation in LDL through a one-electron free radical mechanism; thus the inhibitory actions of.NO and ascorbate may determine low alpha-tocopheryl quinone accumulation in tissues despite increased ONOO- generation.

Assuntos

Peroxidação de Lipídeos/efeitos dos fármacos , Lipoproteínas LDL/metabolismo , Ácido Peroxinitroso/farmacologia , alfa-Tocoferol/metabolismo , gama-Tocoferol/metabolismo , Ácido Ascórbico/farmacologia , Dióxido de Carbono/farmacologia , Humanos , Cinética , Óxido Nítrico/farmacologia , Oxirredução/efeitos dos fármacos , Ácido Peroxinitroso/administração & dosagem , Ácido Peroxinitroso/antagonistas & inibidores

RESUMO

Human serum albumin (HSA), the most abundant protein in plasma, has been proposed to have an antioxidant role. The main feature responsible for this property is its only thiol, Cys34, which comprises approximately 80% of the total free thiols in plasma and reacts preferentially with reactive oxygen and nitrogen species. Herein, we show that the thiol in HSA reacted with hydrogen peroxide with a second-order rate constant of 2.26 M(-1) s(-1) at pH 7.4 and 37 degrees C and a 1:1 stoichiometry. The formation of intermolecular disulfide dimers was not observed, suggesting that the thiol was being oxidized beyond the disulfide. With the reagent 7-chloro-4-nitrobenzo-2-oxa-1,3-diazol (NBD-Cl), we were able to detect the formation of sulfenic acid (HSA-SOH) from the UV-vis spectra of its adduct. The formation of sulfenic acid in Cys34 was confirmed by mass spectrometry using 5,5-dimethyl-1,3-cyclohexanedione (dimedone). Sulfenic acid was also formed from exposure of HSA to peroxynitrite, the product of the reaction between nitric oxide and superoxide radicals, in the absence or in the presence of carbon dioxide. The latter suggests that sulfenic acid can also be formed through free radical pathways since following reaction with carbon dioxide, peroxynitrite yields carbonate radical anion and nitrogen dioxide. Sulfenic acid in HSA was remarkably stable, with approximately 15% decaying after 2 h at 37 degrees C under aerobic conditions. The formation of glutathione disulfide and mixed HSA-glutathione disulfide was determined upon reaction of hydrogen peroxide-treated HSA with glutathione. Thus, HSA-SOH is proposed to serve as an intermediate in the formation of low molecular weight disulfides, which are the predominant plasma form of low molecular weight thiols, and in the formation of mixed HSA disulfides, which are present in approximately 25% of circulating HSA.

Assuntos

4-Cloro-7-nitrobenzofurazano/análogos & derivados , Peróxido de Hidrogênio/farmacologia , Oxidantes/farmacologia , Ácido Peroxinitroso/farmacologia , Albumina Sérica/efeitos dos fármacos , Ácidos Sulfênicos/metabolismo , Tirosina/análogos & derivados , Dissulfetos/metabolismo , Corantes Fluorescentes , Radicais Livres , Glutationa/química , Glutationa/metabolismo , Humanos , Cinética , Oxirredução , Oxigênio/química , Albumina Sérica/metabolismo , Compostos de Sulfidrila/química , Compostos de Sulfidrila/metabolismo , Tirosina/metabolismo

RESUMO

A key early event in the development of atherosclerosis is the oxidation of low density lipoprotein (LDL) via different mechanisms including free radical reactions with both protein and lipid components. Nitric oxide (( small middle dot)NO) is capable of inhibiting LDL oxidation by scavenging radical species involved in oxidative chain propagation reactions. Herein, the diffusion of ( small middle dot)NO into LDL is studied by fluorescence quenching of pyrene derivatives. Selected probes 1-(pyrenyl)methyltrimethylammonium (PMTMA) and 1-(pyrenyl)-methyl-3-(9-octadecenoyloxy)-22,23-bisnor-5-cholenate (PMChO) were chosen so that they could be incorporated at different depths of the LDL particle. Indeed, PMTMA and PMChO were located in the surface and core of LDL, respectively, as indicated by changes in fluorescence spectra, fluorescence quenching studies with water-soluble quenchers and the lifetime values (tau(o)) of the excited probes. The apparent second order rate quenching constants of ( small middle dot)NO (k(NO)) for both probes were 2.6-3.8 x 10(10) m(-1) s(-1) and 1.2 x 10(10) m(-1) s(-1) in solution and native LDL, respectively, indicating that there is no significant barrier to the diffusion of ( small middle dot)NO to the surface and core of LDL. Nitric oxide was also capable of diffusing through oxidized LDL. Considering the preferential partitioning of ( small middle dot)NO in apolar milieu (6-8 for n-octanol:water) and therefore a larger ( small middle dot)NO concentration in LDL with respect to the aqueous phase, a corrected k(NO) value of approximately 0.2 x 10(10) m(-1) s(-1) can be determined, which still is sufficiently large and consistent with a facile diffusion of ( small middle dot)NO through LDL. Applying the Einstein-Smoluchowsky treatment, the apparent diffusion coefficient (D(')NO) of ( small middle dot)NO in native LDL is on average 2 x 10(-5) cm(2) s(-1), six times larger than that previously reported for erythrocyte plasma membrane. Thus, our observations support that ( small middle dot)NO readily traverses the LDL surface accessing the hydrophobic lipid core of the particle and affirm a role for ( small middle dot)NO as a major lipophilic antioxidant in LDL.

Assuntos

Corantes Fluorescentes/metabolismo , Lipoproteínas LDL/metabolismo , Óxido Nítrico/metabolismo , Difusão , Corantes Fluorescentes/química , Humanos , Iodetos/metabolismo , Lipoproteínas LDL/química , Estrutura Molecular , Óxido Nítrico/química , Oxirredução , Pirenos/química , Pirenos/metabolismo , Espectrometria de Fluorescência , Triptofano/metabolismo

RESUMO

Nitric oxide (.NO) is a free radical species synthesized by the oxidation of the amino acid L-arginine to citrulline, by the action of the enzyme nitric oxide synthase (NOS). Nitric oxide has been recognized as a key mediator of diverse physiological functions by direct interactions with critical biomolecules. In addition, nitric oxide can up- or downregulate biological oxidations and therefore modulate free radical mediated injury. Nitric oxide reaction with superoxide radical (O2.-) leads to the formation of a strong oxidizing and cytotoxic molecule, peroxynitrite anion (ONOO-). Peroxynitrite is a much stronger oxidant than any of its precursors being capable of oxidizing and/or nitrating a significant number of biomolecules including protein and nonprotein thiols, different amino acids, lipids and DNA; it has been shown that peroxynitrite is cytotoxic against bacteria, parasite and mammalian cells and has been proposed to participate in various pathological states. On the other hand, nitric oxide can also inhibit free radical reactions by a series of different mechanisms at the molecular level. Nitric oxide can bind to iron and inhibit metal-mediated free radical chemistry, it can terminate free radical processes via combination reactions with free radical intermediates and it can cause redirection of superoxide-mediated toxicity. The dual role of nitric oxide in free radical-mediated oxidations is clearly demonstrated in the oxygen radical-mediated lipid oxidation model, where low fluxes of nitric oxide promete lipid oxidation via formation of the reactive peroxynitrite while under excess nitric oxide, lipid peroxidation reactions are inhibited due to termination reactions between nitric oxide and lipid radicals.

Assuntos

Óxido Nítrico/fisiologia , Antioxidantes , Radicais Livres , Óxido Nítrico/química , Oxidantes