Formation of peroxynitrite during thiol-mediated reduction of sodium nitroprusside

Aleryani, Samir; Milo, Eva; Kostka, P.

doi:10.1016/s0304-4165(99)00119-1

Cited by 23 publications

(21 citation statements)

References 27 publications

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“…Chondrocyte cell death as a function of increasing concentrations of various NO donor compounds was examined in the alginate bead culture system and quantified using the Live/Dead cell assay. Because the proposed cytotoxic species that are generated by SIN-1 and SNP are shortlived molecules (14,16,22), the effect of the "released" forms of SIN-1 and SNP on chondrocyte cell death was investigated. The released forms of these compounds were generated by preincubating 2.0 mM stock solutions of either SIN-1 or SNP in culture media at 37°C for 24 hours prior to experimental use with chondrocyte cultures.…”

Section: Resultsmentioning

confidence: 99%

“…For these reasons, traditional NO donor compounds such as sodium nitroprusside (SNP) or S-nitroso-N-acetyl-L-penicillamine (SNAP) can be, depending on culture conditions, unreliable sources of exogenous NO production (14). For example, it has been reported that SNP does not spontaneously release NO in the absence of redox activation (14), and the primary by products of the decomposition of SNP have also been reported to include compounds such as the cyanide anion (15) and a potentially cytotoxic pentacyanoferrate complex (16).…”

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confidence: 99%

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Nitric oxide–mediated chondrocyte cell death requires the generation of additional reactive oxygen species

Carlo

Loeser

2002

Arthritis & Rheumatism

227

178

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Objective. Chondrocyte cell death, possibly related to increased production of endogenous nitric oxide (NO), has been observed during the pathogenesis of osteoarthritis and rheumatoid arthritis. The purpose of this study was to investigate the potential role of NO in causing chondrocyte cell death and to determine the contribution of other reactive oxygen species (ROS).Methods. Cell death and cytotoxicity were evaluated in human articular chondrocytes in response to various NO donor compounds with and without agents that stimulate or inhibit the production of additional ROS using both the alginate bead and the monolayer culture systems. Cell death was quantified by a total cell count with fluorescent labels, and cytotoxicity was measured as a function of cellular NADH-and NADPHdependent dehydrogenase activity. To determine if the redox status of the chondrocyte could influence the observed effect of NO, cells were preincubated for 24 hours in L-cystine-and glutathione (GSH)-depleted media to reduce intracellular GSH levels, a major defense mechanism against oxidative stress. Apoptosis was analyzed with the quantification of histoneassociated DNA fragments. Conclusion. These results show that NO by itself is not cytotoxic to cultured chondrocytes and can even be protective under certain conditions of oxidative stress. Chondrocyte cell death from NO occurs under conditions where other ROS are also generated. Results. Treatment of chondrocytes with peroxynitrite (ONOONitric oxide (NO) participates in the normal functioning of a wide array of mammalian processes, including vasodilation, inhibition of platelet aggregation, neurotransmission, and macrophage-mediated immunity (1-4). Paradoxically, however, NO has also been proposed to be the cytotoxic species responsible for an increasing number of pathologic disorders, including rheumatic (5) and neurodegenerative (6) diseases. Expression of inducible nitric oxide synthase (iNOS) has been associated with chondrocytes during the pathogenesis of osteoarthritis (OA) (7) and rheumatoid arthritis (RA) (8); however, the exact role of NO in this regard is not fully understood. While it has been reported that NO causes chondrocyte cell death (9,10), other more recent reports have proposed NO to be a physiologic regulator of mitochondrial respiration in chondrocytes (11,12). Moreover, production of high levels of endogenous NO by overexpression of the iNOS gene in transfected chondrocytes did not cause cell death (13).The direct investigation of the function of exogenous NO production on chondrocytes has been hampered by the lack of uniformity that exists between the different types of NO donor compounds. Knowledge of the precise reactive nitrogen species (RNS) that is

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Nitric oxide–mediated chondrocyte cell death requires the generation of additional reactive oxygen species

Carlo

Loeser

2002

Arthritis & Rheumatism

227

178

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“…The incubation medium contained 50 mM buffer MOPS (pH 8.0). The incubation with SNP was carried out with direct environment light to induce photolytic decomposition of the reagent and generate nitric oxide and others reactive nitrogen species [15]. After different incubation times, aliquots were withdrawn and assayed for UDP-GlcPPase activity using the colorimetric method [14].…”

Section: Oxidation Assaymentioning

confidence: 99%

“…We analyzed if the activity of the purified recombinant enzyme could be affected by incubation with three compounds: diamide, hydrogen peroxide, and SNP, which are recognized to be able of modifying the redox status of S-containing moieties. SNP generates nitric oxide-like reactive species able to produce protein S-nitrosylation [15]. Fig.…”

Section: Redox Modulationmentioning

confidence: 99%

Redox regulation of UDP-glucose pyrophosphorylase from Entamoeba histolytica

et al. 2011

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a b s t r a c tAmoebiasis is an intestinal infection caused by the human pathogen Entamoeba histolytica and representing the third leading cause of death by parasites in the world. Host-parasite interactions mainly involve anchored glycoconjugates localized in the surface of the parasitic cell. In protozoa, synthesis of structural oligo-and polysaccharides occurs via UDP-glucose, generated in a reaction catalyzed by UDPglucose pyrophosphorylase. We report the molecular cloning of the gene coding for this enzyme from genomic DNA of E. histolytica and its recombinant expression in Escherichia coli cells. The purified enzyme was kinetically characterized, catalyzing UDP-glucose synthesis and pyrophosphorolysis with V max values of 95 U/mg and 3 U/mg, respectively, and affinity for substrates comparable to those found for the enzyme from other sources. Enzyme activity was affected by redox modification of thiol groups. Different oxidants, including diamide, hydrogen peroxide and sodium nitroprusside inactivated the enzyme. The process was completely reverted by reducing agents, mainly cysteine, dithiothreitol, and thioredoxin. Characterization of the enzyme mutants C94S, C108S, C191S, C354S, C378S, C108/378S, M106S and M106C supported a molecular mechanism for the redox regulation. Molecular modeling confirmed the role of specific cysteine and methionine residues as targets for redox modification in the entamoebic enzyme. Our results suggest that UDP-glucose pyrophosphorylase is a regulated enzyme in E. histolytica. Interestingly, results strongly agree with the occurrence of a physiological redox mechanism modulating enzyme activity, which would critically affect carbohydrate metabolism in the protozoon.

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“…In addition, N-ethylmaleimide significantly inhibited the relaxations to sodium nitroprusside, whereas diamide had no significant effect. When the level of thiols in the tissue drops below some critical point, nitric oxide becomes highly susceptible to oxidation/degradation; thus, its effective concentration is decreased along with soluble guanylate cyclase activation/cGMP synthesis/relaxation (Ignarro et al, 1981;Aleryani et al, 1999;Garcia-Pascual, 1999. Reversal of the effect of N-ethylmaleimide in the presence of exogenously added glutathione and L-cysteine may confirm this suggestion.…”

Section: Discussionmentioning

confidence: 96%

The Relaxant Activity of 4,7-Dimethyl-1,2,5-oxadiazolo[3,4-d]-pyridazine 1,5,6-Trioxide in the Mouse Corpus Cavernosum

Göçmen

Buyuknacar²,

Kots³

et al. 2005

J Pharmacol Exp Ther

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We have studied the effect of an activator of soluble guanylate cyclase 4,7-dimethyl-1,2,5-oxadiazolo [3,4-d]pyridazine 1,5,6-trioxide (FPTO) on the tone and nitrergic relaxation responses of mouse cavernous strips and compared FPTO to a known nitric oxide donor sodium nitroprusside. FPTO thiol-dependently generated nitric oxide measured by polarography and activated purified human soluble guanylate cyclase. FPTO and sodium nitroprusside relaxed the cavernous tissue in a concentration-dependent manner. A nitric-oxide synthase inhibitor N -nitro-L-arginine did not alter the relaxations to FPTO or sodium nitroprusside, whereas soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) suppressed relaxation to FPTO and sodium nitroprusside. Exogenously added thiols L-cysteine or dithiothreitol inhibited the relaxant responses to FPTO but not to sodium nitroprusside, whereas glutathione did not influence the responses to both agents.Thiol alkylation agent N-ethylmaleimide significantly enhanced FPTO-induced relaxation, and thiol-modifying agent diamide inhibited relaxation to FPTO. The potentiating effect of N-ethylmaleimide was neutralized by coadministration of N-ethylmaleimide with glutathione, L-cysteine, dithiothreitol, or ODQ. NEthylmaleimide but not diamide significantly inhibited relaxation induced by sodium nitroprusside. FPTO potently suppressed contraction to electrical field stimulation, which was prevented by glutathione or L-cysteine. In addition, FPTO did not affect relaxation produced by electrical field stimulation in phenylephrine-precontracted tissue. Our results show that FPTO can relax mouse corpus cavernosum and that the relaxant activity of this agent is thiol-and soluble guanylate cyclase-dependent. This effect could be potentiated by N-ethylmaleimide. FPTO does not potentiate nitrergic relaxation induced by electrical field stimulation.The modulatory role of nitric oxide in penile erection has recently been the subject of extensive investigations. Nitric oxide is synthesized by erectile-autonomic nerves and vascular endothelium of the cavernous tissue, and nitric oxidemediated transmission is defined as nitrergic transmission (Saenz de Tejada, 1992). Nitric oxide is a potent activator of soluble guanylate cyclase (sGC), which catalyzes the biosynthesis of cGMP. cGMP causes a trabecular smooth muscle relaxation in the penis, facilitating blood flow into the cavernous tissue and thus eliciting an erection (Saenz de Tejada, 1992).Certain conditions, including aging and vascular and metabolic diseases, can result in the impaired synthesis, release, or bioavailability of NO in the autonomic nerves or endothelium in penile tissue (Saenz de Tejada, 2004). This results in erectile dysfunction due to insufficient relaxation of cavernous smooth muscle and dilation of penile arteries. Certain prodrugs, which can release nitric oxide or nitric oxide-like species under physiological conditions (nitric oxide donors), have been widely used in the therapy of erectile dysfu...

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Formation of peroxynitrite during thiol-mediated reduction of sodium nitroprusside

Cited by 23 publications

References 27 publications

Nitric oxide–mediated chondrocyte cell death requires the generation of additional reactive oxygen species

Nitric oxide–mediated chondrocyte cell death requires the generation of additional reactive oxygen species

Redox regulation of UDP-glucose pyrophosphorylase from Entamoeba histolytica

The Relaxant Activity of 4,7-Dimethyl-1,2,5-oxadiazolo[3,4-d]-pyridazine 1,5,6-Trioxide in the Mouse Corpus Cavernosum

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