Decomposition of S-nitrosothiols: the effects of added thiols

Dicks, Andrew P.; Beloso, Pablo Hervés; Williams, D. Lyn H.

doi:10.1039/a701594a

Cited by 45 publications

(34 citation statements)

References 7 publications

(8 reference statements)

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“…Recently, it has been shown that the decomposition of S-nitrosothiols in aqueous solution is brought about by Cu + , generated by reduction of Cu# + by thiolate ion [35]. Thiols (as thiolate) have a dual effect on the decomposition of S-nitrosothiols, (i) as a reducing agent generating Cu + and (ii) as a complexing agent for Cu# + which is then less available for reduction, the balance of these effects depending on the structure and concentration of the thiol [36]. It has clearly been shown [35] that in the absence of light no reaction occurs, except for a very slow thermal decomposition, when metal ions are removed (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…As to the alternative pathway via S-nitrosylation, different reaction mechanisms have been proposed for the decay of Snitrosothiols and formation of disulphides [28,35,36]. Disulphides can be formed via a simple radical pathway by combination of two sulphur-centred radicals (RSd), resulting from the initial decay of S-nitrosothiols with release of NO, and by reaction of RSd with RSNO [28].…”

Section: Discussionmentioning

confidence: 99%

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Nitric oxide induces Zn2+ release from metallothionein by destroying zinc–sulphur clusters without concomitant formation of S-nitrosothiol

Aravindakumar

Ceulemans

Ley

1999

Biochemical Journal

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The reaction of nitric oxide (NO) with metallothionein (MT) has been investigated at neutral pH under strictly anaerobic conditions. It is observed that NO mediates zinc release from MT by destroying zinc-sulphur clusters, but that it does not by itself Snitrosylate MT in contrast to common belief. Zinc release and loss of thiolate groups under anaerobic conditions is found to be much slower than under aerobic conditions. The observed percentage loss of Zn# + and thiolate groups after 3 h of NO treatment are 62 and 39 %, respectively. The reaction of NO with cysteine is reinvestigated and it is found that cysteine is quan-

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nitric oxide induces Zn2+ release from metallothionein by destroying zinc–sulphur clusters without concomitant formation of S-nitrosothiol

Aravindakumar

Ceulemans

Ley

1999

Biochemical Journal

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“…The emitted NO was purged out from the release media with a continuous nitrogen stream and detected by a chemiluminescence method, which is the gold standard for NO release measurements [34,35]. The NO concentration of the purged gas was measured until a plateau occurred in the detected NO concentration, which usually took about 0.5 h. As shown on Figure 3, the microspheres did not show an initial burst release even in the presence of copper(II) ions and ascorbic acid in the release media (PBSACu), which are known to be initiators for SNAP decomposition [36–38]. However, in the presence of EDTA (PBSE), that chelates the copper(II) ions, the NO release was negligible.…”

Section: Resultsmentioning

confidence: 99%

Biodegradable poly(lactic-co-glycolic acid) microspheres loaded with S-nitroso-N-acetyl-D-penicillamine for controlled nitric oxide delivery

Lautner

Meyerhoff

Schwendeman

2016

Journal of Controlled Release

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Nitric oxide (NO) is a fascinating and important endogenous free-radical gas with potent antimicrobial, vasodilating, smooth muscle relaxant, and growth factor stimulating effects. However, its wider biomedical applicability is hindered by its cumbersome administration, since NO is unstable especially in biological environments. In this work, to ultimately develop site-specific controlled release vehicles for NO, the NO donor S-nitroso-N-acetyl-D-penicillamine (SNAP) was encapsulated within poly(lactic-co-glycolic acid) 50:50 (PLGA) microspheres by using a solid-in-oil-in-water emulsion solvent evaporation method. The highest payload was 0.56(±0.01) μmol SNAP/mg microspheres. The release kinetics of the donor were controlled by the bioerosion of the PLGA microspheres. By using an uncapped PLGA (Mw = 24,000 – 38,000) SNAP was slowly released for over 10 days, whereas by using the ester capped PLGA (Mw = 38,000 – 54,000) the release lasted for over 4 weeks. The presence of copper ions and/or ascorbate in solution was necessary to efficiently decompose the released NO donor and obtain sustained NO release. It was also demonstrated that light can be used to induce rapid NO release from the microspheres over several hours. SNAP exhibited excellent storage stability when encapsulated in the PLGA microspheres. These new microsphere formulations may be useful for site-specific administration and treatment of pathologies associated with dysfunction in endogenous NO production, e.g. treatment of diabetic wounds, or in diseases involving other biological functions of NO including vasodilation, antimicrobial, anticancer, and neurotransmission.

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“…This effect is seen at low concentrations of the thiol and occurs as a result of the reduction of Cu# + to Cu + , the active moiety of copper. At higher concentrations, however, GSH acts as a Cu# + chelator, thus enhancing RSNO stability [53]. GSH levels are dependent on many variables, including age [54], exercise, alcohol intake and smoking [55].…”

Section: Potential Side Effects and Interactions Of Rsnosmentioning

confidence: 99%

Potential therapeutic uses for S-nitrosothiols

Richardson

Benjamin

2001

Clinical Science

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The S-nitrosothiols (RSNOs) are thought to represent a circulating endogenous reservoir of nitric oxide (NO), and may have potential as donors of NO, distinct from currently used agents. They have the general formula RSNO, and naturally occurring examples include S-nitrosocysteine, S-nitrosoglutathione and S-nitrosoalbumin, in which R is an amino acid, polypeptide and protein respectively. RSNOs have anti-platelet properties, a theoretical role in the treatment of asthma and the potential to be used as agents to treat infectious diseases ranging from the common cold to AIDS. RSNOs are relatively unstable, being degraded to release NO and the corresponding disulphide. Their stability is influenced by the properties of the R group, heat, light, the presence of transition metal ions (in particular copper) and the presence of other thiols. RSNOs participate in transnitrosation reactions in which the -NO group is transferred to another thiol to form a more stable RSNO. Thus the stability of RSNOs in vivo is difficult to predict, and this has led to the development of more stable analogues, in which the properties of R are modified. Potential interactions of RSNOs include that with ascorbic acid (vitamin C), which enhances the ability of copper to catalyse their degradation. Transnitrosation reactions with thiol-containing enzymes can influence protein function, and the intracellular thiol glutathione, levels of which are influenced by many disease states, can also influence stability. Thus, although RSNOs have many theoretically useful properties, there are also many aspects of their biochemistry that need to be addressed before their therapeutic potential can be fully realized.

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Decomposition of S-nitrosothiols: the effects of added thiols

Cited by 45 publications

References 7 publications

Nitric oxide induces Zn2+ release from metallothionein by destroying zinc–sulphur clusters without concomitant formation of S-nitrosothiol

Nitric oxide induces Zn2+ release from metallothionein by destroying zinc–sulphur clusters without concomitant formation of S-nitrosothiol

Biodegradable poly(lactic-co-glycolic acid) microspheres loaded with S-nitroso-N-acetyl-D-penicillamine for controlled nitric oxide delivery

Potential therapeutic uses for S-nitrosothiols

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