Efficient nitrosation of glutathione by nitric oxide

Kolesnik, Bernd; Palten, Knut; Schrammel, Astrid; Stessel, Heike; Schmidt, Kurt; Mayer, Bernd; Gorren, Antonius C.F.

doi:10.1016/j.freeradbiomed.2013.04.034

Cited by 34 publications

(41 citation statements)

References 52 publications

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“…The assay mixture contained 200 µM NADP + and varying concentrations of 6-phosphogluconate (5,10,25,50, 75, 100, 250 or 500 µM); the assay was initiated by the addition of 20 nM 6PGD. For 6PGD GSNO-treated samples, the assay was initiated with 600 nM enzyme.…”

Section: Pgd Assaymentioning

confidence: 99%

“…Analysis of the metabolic differences in conjunction with the previously published proteomics study led to the identification of 21 metabolic enzymes that may be modulated by Snitrosation (23). These metabolic enzymes were found to be S-nitrosated in the previous proteomics study with upregulated substrate and downregulated product (or vice versa) (18,25,26), but it is important to note that GSNO may not be the relevant nitrosating agent that led to the observed S-nitrosation of these enzymes in mice. All four of the tested enzymes were inhibited upon GSNO treatment.…”

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confidence: 90%

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Comparative and integrative metabolomics reveal that S-nitrosation inhibits physiologically relevant metabolic enzymes

Bruegger¹,

Smith²,

Wynia-Smith³

et al. 2018

Journal of Biological Chemistry

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Cysteine S-nitrosation is a reversible posttranslational modification mediated by nitric oxide (•NO)-derived agents. S-nitrosation participates in cellular signaling and is associated with several diseases such as cancer, cardiovascular diseases, and neuronal disorders. Despite the physiological importance of this nonclassical •NO signaling pathway, little is understood about how much S-nitrosation affects protein function. Moreover, identifying physiologically relevant targets of S-nitrosation is difficult because of the dynamics of transnitrosation and a limited understanding of the physiological mechanisms leading to selective protein S-nitrosation. To identify proteins whose activities are modulated by S-nitrosation, we performed a metabolomics study comparing wild-type and endothelial nitric oxide synthase (eNOS) knockout mice. We integrated our results with those of a previous proteomics study that identified physiologically relevant S-nitrosated cysteines, and we found that the activity of at least 21 metabolic enzymes might be regulated by Snitrosation. We cloned, expressed, and purified four of these enzymes and observed that S-nitrosation inhibits the metabolic enzymes 6-phosphogluconate dehydrogenase (6PGD), Δ1-pyrroline-5-carboxylate dehydrogenase (ALDH4A1), catechol-O-methyltransferase (COMT), and D-3-phosphoglycerate dehydrogenase (PHGDH). Furthermore, using sitedirected mutagenesis, we identified the predominate cysteine residue influencing the observed activity changes in each enzyme. In summary, using an integrated metabolomics approach, we have identified several physiologically relevant S-nitrosation targets, including metabolic enzymes, which are inhibited by this modification, and have found the cysteines modified by S-nitrosation in each enzyme.Nitric oxide (•NO) is an important signaling molecule in vertebrate tissue that controls physiological processes including vasodilation, neurotransmission, and platelet aggregation (1-3).•NO is biosynthesized by the three mammalian isoforms of nitric oxide synthase (NOS). Endothelial (eNOS) and neuronal NOS (nNOS) produce picomolar to nanomolar concentrations of •NO for cellular signaling, while inducible NOS (iNOS) produces •NO at cytotoxic concentrations in the low micromolar range at sites of infection (4,5). The most thoroughly characterized •NO signaling pathway involves the enzyme soluble guanylate cyclase (sGC) (6).•NO produced by NOS freely diffuses into adjacent cells where it activates sGC to increase the concentration of the secondary messenger cyclic guanosine monophosphate (cGMP) that activates downstream signaling pathways. S-nitrosation Modifies Metabolic Enzyme Function 2Another important, though less well understood, signaling mechanism involving •NO is cysteine S-nitrosation. S-nitrosation is a posttranslational modification of cysteine residues by which an S-nitrosothiol is initially formed via a oneelectron oxidation. Once formed, S-nitrosothiols can be transferred through an intermediate transnitrosating agent such as S-...

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Section: Pgd Assaymentioning

confidence: 99%

mentioning

confidence: 90%

Comparative and integrative metabolomics reveal that S-nitrosation inhibits physiologically relevant metabolic enzymes

Bruegger¹,

Smith²,

Wynia-Smith³

et al. 2018

Journal of Biological Chemistry

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“…It should also be noted that nitrite and SNO production from NO are negligible in the absence of O 2 [9; 11; 56; 57], indicating that the oxidation of NO per Reaction 1 is a prerequisite. The NO 2 · and N 2 O 3 produced in Reaction 1 and 2 respectively, can serve as substrates for subsequent reactions that produce either nitrite or SNO, and it is likely that both sets of pathways occur in plasma [56] (also reviewed by Broniowska et al [58]).…”

Section: Discussionmentioning

confidence: 99%

“…The reactions consuming NO in plasma are not well characterized however. Although NO can react with O 2 in an autoxidation reaction that is second order with respect to NO [8; 9], in oxygenated aqueous buffer this reaction progresses too slowly to account for measured rates of plasma NO disappearance [6; 10; 11]. The copper-containing protein ceruloplasmin (Cp) has been proposed to mediate conversion of NO to nitrite and S-nitrosothiols (SNO) in plasma [6; 12], but the relatively rapid rate of NO disappearance from plasma is sustained even in the absence of Cp [13], suggesting other pathways are involved.…”

Section: Introductionmentioning

confidence: 99%

Postprandial lipids accelerate and redirect nitric oxide consumption in plasma

et al. 2016

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Nitric oxide (NO) and O2 are both three- to four-fold more soluble in biological lipids than in aqueous solutions. Their higher concentration within plasma lipids accelerates NO autoxidation to an extent that may be of importance to overall NO bioactivity. This study was undertaken to test the hypothesis that increased plasma lipids after a high-fat meal appreciably accelerate NO metabolism and alter the byproducts formed. We found that plasma collected from subjects after consumption of a single high-fat meal had a higher capacity for NO consumption and consumed NO more rapidly compared to fasting plasma. This increased NO consumption showed a direct correlation with plasma triglyceride concentrations (p=0.006). The accelerated NO consumption in postprandial plasma was reversed by removal of the lipids from the plasma, was mimicked by the addition of hydrophobic micelles to aqueous buffer, and could not be explained by the presence of either free hemoglobin or ceruloplasmin. The products of NO consumption were shifted in postprandial plasma, with 55% more nitrite (n=12, p=0.002) but 50% less SNO (n=12, p=0.03) production compared to matched fasted plasma. Modeling calculations indicated that NO autoxidation was accelerated by about 48-fold in the presence of plasma lipids. We conclude that postprandial triglyceride-rich lipoproteins exert a significant influence on NO metabolism in plasma.

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“…S-Nitrosylation was thought to be controlled principally through the regulation of NO biosynthesis. Emerging evidences, however, indicate that nitrosothiol (SNO) turnover may provide an alternative regulatory mechanism [3,4]. S-Nitrosylation of the antioxidant tripeptide glutathione forms S-nitrosoglutathione (GSNO), which is thought to function as a mobile reservoir of NO bioactivity [5].…”

Section: Introductionmentioning

confidence: 99%

Detection of S-nitrosylated protein by surface plasmon resonance

Wang

Kong

Zhou

et al. 2015

Sensing and Bio-Sensing Research

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a b s t r a c t S-Nitrosylation has recently emerged as an important posttranslational modification of proteins and is becoming an intensive field of research in plants. Protein S-nitrosation, a reversible post-translation modification of cysteine, affects many cell signaling pathways and plays critical roles in redox-sensitive cell signaling. Changes in protein function effectively transmit biological signals and thus provide a framework for elucidating signaling networks. This paper presented a new, universal immunosensor for detection of S-nitrosylated proteins. Electrochemical impedance spectroscopy (EIS) and atomic force microscope (AFM) were used to estimate the formation of self-assembled film. This method was based on the specific binding characteristics of biotin-streptavidin, using Biotin-HPDP labeled protein sulfhydryl group as the substrate to detect proteins. The sensor was used to detect bovine serum albumin (BSA), nitrosylated BSA and denitrosylated BSA. The results showed that 90.61% of nitrosylated BSA were reduced, verifying that protein S-nitrosylation is a reversible and effective post-translation modification. This method was successfully applied to detect S-nitrosylated protein in Feicheng peach. The results showed good repeatability and precision. This method provided a molecular basis for further exploring the mechanism of S-nitrosylation of proteins in plants.

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Efficient nitrosation of glutathione by nitric oxide

Cited by 34 publications

References 52 publications

Comparative and integrative metabolomics reveal that S-nitrosation inhibits physiologically relevant metabolic enzymes

Comparative and integrative metabolomics reveal that S-nitrosation inhibits physiologically relevant metabolic enzymes

Postprandial lipids accelerate and redirect nitric oxide consumption in plasma

Detection of S-nitrosylated protein by surface plasmon resonance

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