Generation of nitric oxide from S-nitrosothiols using protein-bound Cu2+ sources

Dicks, Andrew P.; Williams, D. Lyn H.

doi:10.1016/s1074-5521(96)90133-7

Cited by 132 publications

(92 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…33,34 It releases NO by photolysis, 35 catalysis by copper ions, 36,37 or by transnitrosation to form S-nitrosocysteine, 38 a less-stable compound, and is known to produce only mild hypotensive effects. 24,25 NO is a potent vasodilator produced from L-arginine by NO synthase (NOS) that has been shown to mediate endothelium-dependent vasodilation 39,40 and play a major role in maintaining resting cerebral vascular tone.…”

Section: Discussionmentioning

confidence: 99%

Effects of S -Nitrosoglutathione on Acute Vasoconstriction and Glutamate Release After Subarachnoid Hemorrhage

Sehba

Ding

Chereshnev

et al. 1999

Stroke

101

View full text Add to dashboard Cite

Background and Purpose-Subarachnoid hemorrhage (SAH) causes acute vasoconstriction that contributes to ischemic brain injury shortly after the initial bleed. It has been theorized that decreased availability of nitric oxide (NO) may contribute to acute vasoconstriction. Therefore we examined the effect of the NO donor N-nitroso glutathione (GSNO) on acute vasoconstriction and early ischemic glutamate release after experimental SAH. Methods-SAH was induced by the endovascular suture method in anesthetized rats. GSNO (1 mol/L/kg, nϭ31) or saline (nϭ21) was injected 5 minutes after SAH. Sham-operated rats received GSNO (1 mol/L/kg, nϭ5) 5 minutes after sham surgery. Arterial and intracranial pressures, cerebral blood flow (CBF), and extracellular glutamate release were measured serially for 60 minutes after SAH. SAH size was determined, and vascular measurements were made histologically. Results-GSNO had no effect on resting blood pressure, intracranial pressure, cerebral perfusion pressure, or CBF in sham-operated animals. However, administration of GSNO after SAH was associated with significantly increased CBF (161.6Ϯ26.6% versus saline 37. Key Words: cerebral blood flow Ⅲ glutamates Ⅲ nitric oxide Ⅲ subarachnoid hemorrhage Ⅲ vasoconstriction C erebral arteries respond to subarachnoid hemorrhage (SAH) with a biphasic contraction that begins minutes after the bleed and delayed vasospasm more than 48 hours later. 1-3 Although a great deal is known about the mechanisms and management of delayed vasospasm, less is known about the physiology, treatment, and importance of acute vasoconstriction. Different mechanisms may underlie the 2 processes, 4 and a great variety have been implicated. [5][6][7][8][9][10][11] Recently we have shown that acute vasoconstriction is associated with decreased cerebral blood flow (CBF), ischemic glutamate release, and premature mortality after experimental SAH. 12 If acute vasoconstriction could be pharmacologically attenuated, then SAH-induced brain injury could potentially be reduced.Resting cerebrovascular tone is maintained by a balance between opposing vasoconstrictive and vasodilatory forces, and both are pathologically altered in the acute phases of SAH. One of the most important of these is the resting vasodilatory influence of nitric oxide (NO). NO has been shown to induce endothelium-dependent vasodilatation via a cGMP-mediated See Editorial Comment, page 1961 mechanism. 13 Loss of endothelium-mediated vasodilatation 14,15 and decreased cGMP production 16,17 have been shown to contribute to vasospasm after SAH.Because administration of an NO donor after SAH should potentially restore c-GMP-dependent vasodilatation, a number of different NO donors have been tested for their ability to attenuate delayed vasospasm. 18 -21 Recent studies have suggested that sodium nitroprusside administered intrathecally 22 or intra-arterially 23 increases CBF acutely after SAH. In preliminary studies we have found that it also causes profound hypotension in this setting (J.B. Bederson, MD, et al, ...

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of S -Nitrosoglutathione on Acute Vasoconstriction and Glutamate Release After Subarachnoid Hemorrhage

Sehba

Ding

Chereshnev

et al. 1999

Stroke

101

View full text Add to dashboard Cite

show abstract

“…12 Bioavailable reductants, such as Asc, in the presence of transition metals (eg, copper [Cu]) are required for release of biologically active NO from nitrosylated thiols. 13 Cu in the presence of Asc is capable to undergoing 1-electron oxidation-reduction conversion. Reaction scheme typically includes the following reactions:…”

mentioning

confidence: 99%

S -Nitrosoalbumin–Mediated Relaxation Is Enhanced by Ascorbate and Copper

et al. 2005

View full text Add to dashboard Cite

Abstract-S-nitrosoalbumin (SNO-Alb) is a major reservoir of releasable nitric oxide (NO) in plasma. In preeclampsia, a pregnancy-specific disorder associated with endothelial dysfunction, we previously found significant elevations in plasma SNO-Alb concentrations and decreased plasma ascorbate (Asc) levels. This increased SNO-Alb may result from low-plasma Asc if Asc, along with transition metals (eg, copper [Cu]) are necessary for release of NO from S-nitrosothiols. We propose that vasodilator effects of SNO-Alb, mediated by release of NO, are fully realized only when Asc/Cu availability is sufficient. Relaxation responses to SNO-Alb or the control reduced human serum albumin (SH-Alb), and responses to pooled plasma from normal or preeclamptic pregnancies were examined in isolated mouse arteries. Arteries preconstricted with phenylephrine were exposed to SNO-Alb or SH-Alb at physiologically relevant concentrations. When free Cu was added in excess (10 mol/L), NO release was not dependent on Asc. However, when Cu was added at lower (physiological) levels, NO release was dependent on Asc. The addition of Asc and Cu to SNO-Alb stimulated vasodilatory responses in isolated arteries Ͼ90%, whereas no change in the SH-Alb (5%) response was observed. Preeclampsia plasma with higher levels of SNO-Alb caused arteries to relax 44.1Ϯ4.7%, whereas normal pregnancy plasma caused 11.9Ϯ4.2% relaxation (Pϭ0.007). These data indicate that SNO-Alb alone or in plasma can act as a potent vasodilator, and that sufficient Asc/Cu promotes this action. We suggest that the higher circulating levels of SNO-Alb, in women with preeclampsia, reflect a deficiency in Asc/Cu-mediated release of NO from SNO-Alb. Key Words: preeclampsia Ⅲ pregnancy Ⅲ nitric oxide Ⅲ oxidative stress Ⅲ antioxidants P reeclampsia is a major cause of maternal and neonatal morbidity and mortality. The clinical manifestations of this pregnancy-specific disorder include hypertension and proteinuria developing after 20 weeks of gestation. Placental abnormalities and maternal endothelial dysfunction/activation are thought to contribute to vasospasm and the onset of the maternal syndrome. It has been hypothesized that oxidative stress plays a role in the pathophysiology of preeclampsia. Evidence of oxidative stress in combination with profound depletion of plasma ascorbate (Asc) has been reported in women with preeclampsia. [1][2][3][4] Asc concentrations in women with preeclampsia are nearly half those of matched normal pregnant controls (Ϸ40 versus 25 mol/L). 5 The implications of this reduction in plasma Asc are currently not clear. Plasma Asc levels are inversely related to blood pressures in men without a history of hypertension. 6,7 Asc and vitamin E supplementation in women at high risk for preeclampsia was associated with a reduction in markers of endothelial dysfunction and in the incidence of preeclampsia. 5,8 Although the decreased incidence of preeclampsia was associated with decreased biochemical indices of oxidative stress and poor placental function, the me...

show abstract

“…For many RSNOs, this rate of decomposition is effectively zero order, suggesting that the formation of Cu + is the rate limiting step (70). Protein-bound copper sources are also capable of generating NO from RSNOs (12). Overall, RSNO decomposition rate does not depend on the rate of thermolysis but on the presence of copper ions in solution, light, and the proximity of other thiolates.…”

Section: S-nitrosothiol Formation and Decompositionmentioning

confidence: 97%

Chemical Methods for the Direct Detection and Labeling of S-Nitrosothiols

Bechtold

King

2012

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Significance: Posttranslational modification of proteins through phosphorylation, glycosylation, and oxidation adds complexity to the proteome by reversibly altering the structure and function of target proteins in a highly controlled fashion. Recent Advances: The study of reversible cysteine oxidation highlights a role for this oxidative modification in complex signal transduction pathways. Nitric oxide (NO), and its respective metabolites (including reactive nitrogen species), participates in a variety of these cellular redox processes, including the reversible oxidation of cysteine to S-nitrosothiols (RSNOs). RSNOs act as endogenous transporters of NO, but also possess beneficial effects independent of NO-related signaling, which suggests a complex and versatile biological role. In this review, we highlight the importance of RSNOs as a required posttranslational modification and summarize the current methods available for detecting S-nitrosation. Critical Issues: Given the limitations of these indirect detection methods, the review covers recent developments toward the direct detection of RSNOs by phosphine-based chemical probes. The intrinsic properties that dictate this phosphine/ RSNO reactivity are summarized. In general, RSNOs (both small molecule and protein) react with phosphines to yield reactive S-substituted aza-ylides that undergo further reactions leading to stable RSNO-based adducts.

show abstract

Generation of nitric oxide from S-nitrosothiols using protein-bound Cu2+ sources

Abstract: These results show clearly that amino-acid- and protein-bound Cu2+ can be reduced by thiolate ion to Cu+, which will generate NO from RSNO species, thus providing a realistic model for these reactions in vivo.

Cited by 132 publications

References 17 publications

Effects of S -Nitrosoglutathione on Acute Vasoconstriction and Glutamate Release After Subarachnoid Hemorrhage

Effects of S -Nitrosoglutathione on Acute Vasoconstriction and Glutamate Release After Subarachnoid Hemorrhage

S -Nitrosoalbumin–Mediated Relaxation Is Enhanced by Ascorbate and Copper

Chemical Methods for the Direct Detection and Labeling of S-Nitrosothiols

Contact Info

Product

Resources

About