<i>P</i>-Nitrosophosphate Compounds:  New N−O Heterodienophiles and Nitroxyl Delivery Agents

Rw, Ware; Sb, King

doi:10.1021/jo001230z

Cited by 33 publications

(21 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Then, an ATP molecule, bound tightly to the nucleotide-binding motif of Srxn1, is brought into close proximity to the S-nitrosothiol of Prx2 (35,37). The direct attack of the ATP phosphate group on Cys-SNO generates a P-nitrosophosphine oxide, a very unstable subproduct of the reaction containing both the phosphate and NO groups (40). Finally, this P-nitrosophosphine oxide hydrolyzes to produce nitroxyl (40), which quickly dimerizes, generating nitrous oxide (N 2 O).…”

Section: Discussionmentioning

confidence: 99%

“…The direct attack of the ATP phosphate group on Cys-SNO generates a P-nitrosophosphine oxide, a very unstable subproduct of the reaction containing both the phosphate and NO groups (40). Finally, this P-nitrosophosphine oxide hydrolyzes to produce nitroxyl (40), which quickly dimerizes, generating nitrous oxide (N 2 O). In general, strong nucleophiles will attack the N in S-nitrosothiol compounds.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Role of sulfiredoxin as a peroxiredoxin-2 denitrosylase in human iPSC-derived dopaminergic neurons

Sunico

Sultan

Nakamura

et al. 2016

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

View full text Add to dashboard Cite

Recent studies have pointed to protein S-nitrosylation as a critical regulator of cellular redox homeostasis. For example, S-nitrosylation of peroxiredoxin-2 (Prx2), a peroxidase widely expressed in mammalian neurons, inhibits both enzymatic activity and protective function against oxidative stress. Here, using in vitro and in vivo approaches, we identify a role and reaction mechanism of the reductase sulfiredoxin (Srxn1) as an enzyme that denitrosylates (thus removing -SNO) from Prx2 in an ATP-dependent manner. Accordingly, by decreasing S-nitrosylated Prx2 (SNO-Prx2), overexpression of Srxn1 protects dopaminergic neural cells and human-induced pluripotent stem cell (hiPSC)-derived neurons from NO-induced hypersensitivity to oxidative stress. The pathophysiological relevance of this observation is suggested by our finding that SNO-Prx2 is dramatically increased in murine and human Parkinson's disease (PD) brains. Our findings therefore suggest that Srxn1 may represent a therapeutic target for neurodegenerative disorders such as PD that involve nitrosative/oxidative stress.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Role of sulfiredoxin as a peroxiredoxin-2 denitrosylase in human iPSC-derived dopaminergic neurons

Sunico

Sultan

Nakamura

et al. 2016

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

View full text Add to dashboard Cite

show abstract

“…12 This reduced form of NO has unique effects on vascular smooth muscle distinct from other redox forms of NO. 13 15 to reverse cerebral vasospasm, 16 and to reduce pulmonary vascular pressures and improve oxygenation in acute lung injury 17 ; this latter benefit was observed using an aerosolized preparation.…”

Section: Direct Donorsmentioning

confidence: 99%

Nitric Oxide Donors and Cardiovascular Agents Modulating the Bioactivity of Nitric Oxide

Ignarro

Napoli

Loscalzo

2002

Circulation Research

438

335

View full text Add to dashboard Cite

Abstract-Nitric oxide (NO) mediates multiple physiological and pathophysiological processes in the cardiovascular system. Pharmacological compounds that release NO have been useful tools for evaluating the pivotal role of NO in cardiovascular physiology and therapeutics. These agents constitute two broad classes of compounds, those that release NO or one of its redox congeners spontaneously and those that require enzymatic metabolism to generate NO. In addition, several commonly used cardiovascular drugs exert their beneficial action, in part, by modulating the NO pathway. Here, we review these classes of agents, summarizing their fundamental chemistry and pharmacology, and provide an overview of their cardiovascular mechanisms of action. ysfunction of the normally protective endothelium is found in several cardiovascular diseases, including atherosclerosis, hypertension, heart failure, coronary heart disease, arterial thrombotic disorders, and stroke. [1][2][3][4][5][6] Endothelial dysfunction leads to nitric oxide (NO) deficiency, 1,6 -11 which has been implicated in the underlying pathobiology of many of these disorders (NO insufficiency states). (For a detailed overview of the role of NO in cardiovascular biology and pathobiology, the reader is referred to Loscalzo and Vita. 3 ) NO insufficiency may reflect an absolute deficit of NO (synthesis), impaired availability of bioactive NO, or enhanced NO inactivation. Whatever its biochemical basis, NO insufficiency limits NO-mediated signal transduction of normal or protective physiological processes. In light of this pathobiology, replacement or augmentation of endogenous NO by exogenously administered NO donors has provided the foundation for a broad field of pharmacotherapeutics in cardiovascular medicine.Organic nitrate and nitrite esters represent a time-honored class of NO-donating agents used in cardiovascular therapeutics since the 19th century. These agents have direct vasoactive effects that have been used to treat ischemic heart disease, heart failure, and hypertension for many years. Treatment with conventional nitrate preparations is limited by their therapeutic half-life, systemic absorption with potentially adverse hemodynamic effects, and drug tolerance. 1,6 To overcome these limitations, novel NO donors that offer selective effects, a prolonged half-life, and a reduced incidence of drug tolerance have been developed. NO donors are pharmacologically active substances that spontaneously release, or are metabolized to, NO or its redox congeners. In the present article, we review our current understanding of NO-donating compounds and of cardiovascular drugs that modulate the bioactivity of endogenously produced NO. NO DonorsBecause of the limited utility of authentic NO gas in many experimental systems and the short half-life of NO in vivo, compounds that have the capacity to release NO have been widely used as therapeutic agents and as pharmacological tools to investigate the role of NO in cardiovascular physiology and pathophysiology. Several NO do...

show abstract

“…NO À donors, generated spontaneously under physiological conditions (Ware and King, 2000) from AngeliÕs salt ( Fig. 1, Table 1) and p-nitrosophosphate compounds, have not yet been tested in humans despite the fact that the effects of NO À are unique when compared to other redox forms of NO (Ellis et al, 2000) (Fig.…”

Section: Direct Nitric Oxide Donorsmentioning

confidence: 99%

Application of pharmaceuticals to nitric oxide

Low

2005

Molecular Aspects of Medicine

View full text Add to dashboard Cite

P-Nitrosophosphate Compounds: New N−O Heterodienophiles and Nitroxyl Delivery Agents

Cited by 33 publications

References 15 publications

Role of sulfiredoxin as a peroxiredoxin-2 denitrosylase in human iPSC-derived dopaminergic neurons

Role of sulfiredoxin as a peroxiredoxin-2 denitrosylase in human iPSC-derived dopaminergic neurons

Nitric Oxide Donors and Cardiovascular Agents Modulating the Bioactivity of Nitric Oxide

Application of pharmaceuticals to nitric oxide

Contact Info

Product

Resources

About