Dynamic state of S-nitrosothiols in human plasma and whole blood

Jourd’heuil, David; Hallén, Katarina; Feelisch, Martin; Grisham, Matthew B.

doi:10.1016/s0891-5849(99)00257-9

Cited by 146 publications

(98 citation statements)

References 48 publications

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“…The latter can be considered as a relatively constant NO pool for storage and transport purposes. 10 A slight drop of total plasma RSNO 10 minutes after PFC administration (the time of maximal LMW RSNO increase) reflects the process of PFC-mediated redistribution of NO from its HMW depot to actively used LMW RSNO.…”

Section: Pfc-mediated Catalysis Of Rsnos In Vivo and Control Of Bloodmentioning

confidence: 99%

“…[3][4][5][6][7] Because RSNOs are relatively stable and can release NO when required on reaction with various reducing agents, 8,9 they may serve as a buffering system that magnifies the range of NO action along the vascular tree. 10,11 Although the pharmacological potential of RSNO is well appreciated, [12][13][14] the role of plasma NO and the mechanism of endogenous RSNO formation under physiological conditions are a source of considerable debate. 15 The apparent limitation for plasma NO to exert its biological function is the constant presence of abundant hemoglobin (10 mmol/L) from red blood cells that converts NO into inactive metabolites at near-diffusion-limited rates.…”

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confidence: 99%

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Control of Plasma Nitric Oxide Bioactivity by Perfluorocarbons

et al. 2004

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Background-Perfluorocarbons (PFCs) are promising blood substitutes because of their chemical inertness and unparalleled ability to transport and upload O 2 and CO 2 . Here, we report that PFC emulsions also efficiently absorb and transport nitric oxide (NO). Methods and Results-Accumulation of NO and O 2 in PFC micelles results in rapid NO oxidation and generation of reactive NO x species. Such micellar catalysis of NO oxidation leads to formation of vasoactive S-nitrosothiols (RSNO) in vitro and in vivo as detected electrochemically. The efficiency of PFC-mediated S-nitrosation depends on the amount of PFC in aqueous solution. The optimal PFC concentration that produced the maximum level of RSNO was Ϸ1% (vol/vol). Larger PFC amounts were progressively less efficient in generating RSNO and functioned simply as NO sink. These results explain the characteristic hemodynamic effects of PFCs. Intravenous bolus application of PFC (0.14 g/kg, Ϸ1% vol/vol) to Wistar-Kyoto rats decreased mean arterial pressure significantly (Ϫ10 mm Hg over 40 minutes). PFC-induced hypotension could be further stimulated (Ϫ17 mm Hg over 140 minutes) by exogenous thiols (cysteine and glutathione). In contrast, a larger amount of PFC (1 g/kg, Ϸ7% vol/vol) exhibited a strong hypertensive effect (11 mm Hg over 40 minutes). Conclusions-The present study reveals a physiologically significant pool of endogenous plasma NO and underscores the crucial role of the circulating hydrophobic phase in modulating its bioactivity. The results also establish PFC as a conceptually new pharmacological tool for various cardiovascular complications associated with NO imbalance.

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Section: Pfc-mediated Catalysis Of Rsnos In Vivo and Control Of Bloodmentioning

confidence: 99%

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confidence: 99%

Control of Plasma Nitric Oxide Bioactivity by Perfluorocarbons

et al. 2004

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“…15 and 17-19 and references therein), ⅐ NO carriers such as nitrosothiols refs. 15,17,[19][20][21], NO complexes with transition metals (22, 23), or can result from a direct reaction between ⅐ NO and thiols in the presence of electron acceptors (24). It remains uncertain which pathway dominates in vivo and under what conditions it does so.…”

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confidence: 99%

An autocatalytic mechanism of protein nitrosylation

Nedospasov

Rafikov

Beda

et al. 2000

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

130

100

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Nitros(yl)ation is a widespread protein modification that occurs during many physiological and pathological processes. It can alter both the activity and function of a protein. Nitric oxide ( ⅐ NO) has been implicated in this process, but its mechanism remained uncertain. ⅐ NO is unable to react with nucleophiles under oxygenfree conditions, suggesting that its higher oxides, such as N 2O3, were actually nitrosylating agents. However, low concentrations and short lifespans of these species in vivo raise the question of how they could efficiently locate target proteins. Here we demonstrate that at physiological concentrations of ⅐ NO, N2O3 forms inside protein-hydrophobic cores and causes nitrosylation within the protein interior. This mechanism of protein modification has not been characterized, because all previously described mechanisms (e.g., phosphorylation, acetylation, ADP-ribosylation, etc.) occur via attack on a protein by an external modification agent. Oxidation of ⅐ NO to N2O3 is facilitated by micellar catalysis, which is mediated by the hydrophobic phase of proteins. Thus, a target protein seems to be a catalyst of its own nitrosylation. One of the applications of this finding, as we report here, is the design of specific hydrophobic compounds whose cooperation with ⅐ NO and O 2 allows the rapid inactivation of target enzymes to occur. T he free radical ⅐ NO has important biological functions including vasorelaxation, blood clotting, neuronal plasticity, and cytotoxic activity (for reviews, see refs. 1 and 2). In many cases, the physiological effect of ⅐ NO can be attributed to the S-nitrosylation of target proteins such as hemoglobin (3), serum albumin (4 and 5), transcription factors (6-9), G proteins (10), ion channels (11), and various enzymes (12)(13)(14). Excessive protein nitrosation has been associated also with various pathological situations including myocardial ischemia, atherosclerosis, inflammation, and cancer (for reviews, see refs. 1, 2, 15, and 16). In vivo, nitros(yl)ation can be mediated by dinitrogen trioxide (N 2 O 3 ; refs. 15 and 17-19 and references therein), ⅐ NO carriers such as nitrosothiols refs. 15,17,[19][20][21], NO complexes with transition metals (22, 23), or can result from a direct reaction between ⅐ NO and thiols in the presence of electron acceptors (24). It remains uncertain which pathway dominates in vivo and under what conditions it does so. It is also unclear which mechanism is responsible for the high specificity of S-nitrosylation, when only particular nucleophiles are targeted within a protein while others are left unmodified.⅐ NO reacts with O 2 according to the following stoichiometry:Because ⅐ NO and O 2 are better soluble in hydrophobic solvents than in water, with a partition coefficient (Q) Ͼ Ͼ 1 (25-27), areas of high hydrophobicity can act to increase the local concentration of these molecules by sequestering them from the surrounding aqueous phase. Under aerobic conditions, high local concentrations of ⅐ NO and O 2 in a hydrophobic phase, such as ...

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“…The nitrosothiols have different degrees of stability. Thiol groups in proteins are also nitrosated and are relatively stable [35]. Herein, we have shown that the extract from Conyza canadensis may reduce plasma protein disulfides, but at higher concentration, like peroxynitrite may oxidize protein thiols.…”

Section: Resultsmentioning

confidence: 84%

“…Enzyme homocysteine thiolactone hydrolase that is associated with HDL in plasma protects protein against protein homocysteinylation [35,38]. It should be taken into account the role of this hydrolase in the release of Hcys from homocysteinylated proteins due to C. canadensis action.…”

Section: Referencesmentioning

confidence: 99%

Extract from Conyza canadensis as a modulator of plasma protein oxidation induced by peroxynitrite in vitro

et al. 2010

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Abstract:The antioxidative activity of the extract from Conyza canadensis in plasma treated with peroxynitrite (ONOO -) (0.1 mM) was studied. C. canadensis is known to possess a broad set of pharmacological effects because of content of various antioxidants, antiplatelet and anticoagulant compounds. The aim of our study was to assess if this extract protects plasma proteins against oxidative/nitrative damages induced by ONOO -. The plasma components are continuously exposed to reactive oxygen/nitrogen species action. Peroxynitrite evokes oxidative stress and induces undesirable effects in biological systems and causes damage to biomolecules. The extract from Conyza (50 -2500 mg/ml) caused a dose-dependent reduction of protein nitration by 90%. The oxidation of plasma proteins was diminished by about 75%. ONOO -oxidized the plasma thiol groups and this process was inhibited by tested extract. The level of reduced protein thiols was increased thrice at the lowest concentration of extract (50 mg/ml). The highest concentration of extract decreased twice the level of protein thiols in reduced forms and increased the homocysteine level about 4.5 times. The obtained results demonstrated that the extract from Conyza possesses antioxidative properties in vitro, protects plasma proteins against toxicity induced by peroxynitrite and has modulating effects on thiol/disulfide redox status.

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Dynamic state of S-nitrosothiols in human plasma and whole blood

Cited by 146 publications

References 48 publications

Control of Plasma Nitric Oxide Bioactivity by Perfluorocarbons

Control of Plasma Nitric Oxide Bioactivity by Perfluorocarbons

An autocatalytic mechanism of protein nitrosylation

Extract from Conyza canadensis as a modulator of plasma protein oxidation induced by peroxynitrite in vitro

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