Reaction of Nitroxyl, an Aldehyde Dehydrogenase Inhibitor, with N-Acetyl-L-Cysteine

Shoeman, Don W.; Shirota, Frances N.; DeMaster, Eugene G.; Nagasawa, Hiromichi

doi:10.1016/s0741-8329(99)00056-7

Cited by 58 publications

(60 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Different proteins and enzymes including mammalian and bacterial hemoglobins (49,50), ferrocytochrome c (51), superoxide dismutase (52), and NO synthase (53), as well as decomposition of S-nitrosothiols (34), may give rise to NO Ϫ . The fate of NO Ϫ within the cellular system is unknown, but this unstable species has been reported to react readily with thiols (41,42), and in the presence of molecular oxygen or other oxidants, it can generate other RNS with specific reactivity toward cellular targets (54,55). In the presence of hydrogen peroxide and transition metals, NO Ϫ but not NO appears to cause loss of cell viability by site-specific DNA damage (56).…”

Section: Discussionmentioning

confidence: 99%

“…The extent of these reactions depends upon the composition of the intracellular milieu; in this respect, thiols are known to play a major role because they are preferential sites for the NO groups (33). In particular, NO Ϫ seems to react more readily than NO with sulfydryl moieties (33,41,42). In addition, it is known that certain transition metals, such as Cu 2ϩ and Fe 3ϩ , can catalyze the conversion of NO Ϫ to NO in vitro and in vivo (36,43).…”

Section: Dissecting the Effects Of Nomentioning

confidence: 99%

See 1 more Smart Citation

Induction of Heme Oxygenase 1 by Nitrosative Stress

Naughton

Foresti

Bains

et al. 2002

Journal of Biological Chemistry

106

View full text Add to dashboard Cite

Heme oxygenase, the rate-limiting step in heme degradation to CO and bilirubin, exists in inducible (HO-1) 1 and constitutive (HO-2 and HO-3) isoforms, the synthesis and activities of which are differentially regulated in mammalian tissues (1-3). The common conception that these enzymes are merely components of a catabolic pathway that facilitates the elimination of toxic products from the organism has been disputed by strong evidence demonstrating that endogenously generated CO and bilirubin act as crucial effector molecules in the mitigation of vascular and cellular dysfunction (4 -12). Disparate conditions and a number of pathological states including hypoxia, endotoxic shock, atherosclerosis, and inflammation have been found to promote overexpression of the HO-1 gene and increased heme oxygenase activity (13-18). Although the molecular mechanism(s) leading to HO-1 induction by these and other conditions remains to be fully elucidated, a common denominator that characterizes the prompt stimulation of HO-1 under most circumstances is the transient decrease in cellular glutathione levels and a drastic change in the redox status of the intracellular milieu (15, 19 -21). It is not surprising, therefore, that conditions associated with increased production of reactive oxygen species and reactive nitrogen species (RNS) favor the activation of the HO-1/CO/bilirubin pathway, which is now regarded as an important cellular stratagem to counteract and resist different stress insults (3,22). In the context of redox reactions and signal transduction events that elicit the expression of HO-1 in vascular tissue, the gaseous molecule NO has recently been highlighted as an important biological modulator (see reviews in Refs. 22 and 23; Refs. 15 and 24). NO has been implicated in a wide range of processes critical to normal functions in the cardiovascular, nervous, and immune systems; the cytotoxic nature of NO has also been extensively emphasized when excessive production of this gas is triggered under certain pathological conditions (25). The conception that HO-1 might function to counteract the potential toxic effects evoked by NO first emerged from the discovery that certain NO-releasing agents can stimulate an increase in HO-1 transcript and heme oxygenase activity, resulting in protection against oxidative stress (26 -28). Subsequent reports have confirmed these findings (24, 29 -31), and more recent works have established that NO-related species (such as peroxynitrite and S-nitrosoglutathione) as well as endogenously generated NO and S-nitrosothiols are also capable of 32). In light of the rather complex and diverse chemistry of the NO group, which enables it to exist in a variety of interrelated redox-activated forms, investigations are now required to explore which additional NO * This work was supported by British Heart Foundation Grants PG/ 1999-005 and PG/2001-037 (to R. M.) and PG/2000 and by funds from the Dunhill Medical Trust. The National Heart Research Fund and the Wellcome Trust provided travel grants to p...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Dissecting the Effects Of Nomentioning

confidence: 99%

Induction of Heme Oxygenase 1 by Nitrosative Stress

Naughton

Foresti

Bains

et al. 2002

Journal of Biological Chemistry

106

View full text Add to dashboard Cite

show abstract

“…Fig. 1 (9,19). In the original study by Grätzel et al (4), difficulty in obtaining an accurate NO Ϫ concentration measurement directly after the radiolysis pulse (25,26) that the process of proton transfer involving spin state interconversion is slowed by as much as 10 7 , as compared with spin-conserving proton transfers.…”

Section: Nomentioning

confidence: 99%

“…HNO has biological activity; it can act as a potent cytotoxic agent that causes double-stranded breaks in DNA, depletion of cellular glutathione (16), as well as elicitation of smooth muscle relaxation (17). HNO has been found to be a potent inhibitor of thiol-containing enzymes (18,19) and attenuates the activity of the NMDA receptor via thiol modification, thus providing neuroprotection (20).Much of the fundamental biological chemistry associated with HNO is unknown, aside from the rate constant for dimerization is a typical nucleophile, yet several studies find that HNO generated at physiological pH reacts readily as an electrophile, particularly with thiols, to yield N-hydroxysulfenamide intermediates (9, 21), implying a higher pK a . NO Ϫ and NO react rapidly and irreversibly to form N 2 O 2 Ϫ , a reactive radical anion (6).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

On the acidity and reactivity of HNO in aqueous solution and biological systems

Bartberger

Fukuto

Houk

2001

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

163

View full text Add to dashboard Cite

The gas phase and aqueous thermochemistry and reactivity of nitroxyl (nitrosyl hydride, HNO) were elucidated with multiconfigurational self-consistent field and hybrid density functional theory calculations and continuum solvation methods. The pK a of HNO is predicted to be 7.2 ؎ 1.0, considerably different from the value of 4.7 reported from pulse radiolysis experiments. The ground-state triplet nature of NO ؊ affects the rates of acid-base chemistry of the HNO͞NO ؊ couple. HNO is highly reactive toward dimerization and addition of soft nucleophiles but is predicted to undergo negligible hydration (Keq ‫؍‬ 6.9 ؋ 10 ؊5 ). HNO is predicted to exist as a discrete species in solution and is a viable participant in the chemical biology of nitric oxide and derivatives.T he discoveries of nitric oxide (NO) biosynthesis in mammalian cells and the diverse biological activity associated with NO and NO-derived species (1) have brought intense interest in the physiological chemistry of nitrogen oxides. The chemistry of NO and its biologically accessible oxidized congeners nitrogen dioxide (NO 2 ), nitrite (NO 2 Ϫ ), peroxynitrite (ONOO Ϫ ), dinitrogen trioxide (N 2 O 3 ), and nitrate (NO 3 Ϫ ) is fairly well established (2). By contrast, the reduced congeners such as nitroxyl (HNO) and its conjugate base (NO Ϫ ) are less well understood, and consequently their role in biology is not clear. The importance of HNO or NO Ϫ in biology has often been neglected or dismissed, in part because NO metabolism is thought to be primarily oxidative in nature (3), and because HNO is thought to be only metastable (3), a strong acid (4), and to dimerize readily (5). NO Ϫ is known to react rapidly and irreversibly with NO (6), making the examination of NO Ϫ in the presence of NO difficult. Additionally, HNO might be expected to be electrophilic, and hydration under physiological conditions would serve to attenuate its aqueous reactivity.Nitroxyl (HNO), or its conjugate base, NO Ϫ , is known to be formed under physiological conditions; for example, oxidation of N-hydroxy-L-arginine (an intermediate in NO biosynthesis) (7), reaction of S-nitrosothiols with thiols (8, 9), nitric oxide synthase (10-12), and even direct reduction of NO by mitochondrial cytochrome c (13), may all generate HNO. Nitroxyl has been generated via the interaction of NO with manganese superoxide dismutase (14) and with ubiquinol (15). HNO has biological activity; it can act as a potent cytotoxic agent that causes double-stranded breaks in DNA, depletion of cellular glutathione (16), as well as elicitation of smooth muscle relaxation (17). HNO has been found to be a potent inhibitor of thiol-containing enzymes (18,19) and attenuates the activity of the NMDA receptor via thiol modification, thus providing neuroprotection (20).Much of the fundamental biological chemistry associated with HNO is unknown, aside from the rate constant for dimerization is a typical nucleophile, yet several studies find that HNO generated at physiological pH reacts readily as an electrophile, par...

show abstract

Studies on the Reaction of Reduced Vitamin B₁₂ Derivatives with the Nitrosyl Hydride (HNO) Donor Angeli's Salt: HNO Oxidizes the Transition‐Metal Center of Cob(I)alamin

Subedi

Brasch

2015

Eur J Inorg Chem

View full text Add to dashboard Cite

Although it is well established that nitrosyl hydride (nitroxyl, HNO) reduces transition metals including transition-metal centers of porphyrins and metalloproteins, oxidation of a metal center by HNO has yet to be reported. Kinetic and mechanistic studies on the Co II vitamin B 12 form, cob(II)alamin [Cbl(II)], with the widely used HNO donor Angeli's salt (AS) have been carried out. The stoichiometry of the reaction is Cbl(II)/AS = 1:2, and AS decomposition to give HNO and

show abstract

Reaction of Nitroxyl, an Aldehyde Dehydrogenase Inhibitor, with N-Acetyl-L-Cysteine

Cited by 58 publications

References 14 publications

Induction of Heme Oxygenase 1 by Nitrosative Stress

Induction of Heme Oxygenase 1 by Nitrosative Stress

On the acidity and reactivity of HNO in aqueous solution and biological systems

Studies on the Reaction of Reduced Vitamin B₁₂ Derivatives with the Nitrosyl Hydride (HNO) Donor Angeli's Salt: HNO Oxidizes the Transition‐Metal Center of Cob(I)alamin

Contact Info

Product

Resources

About

Reaction of Nitroxyl, an Aldehyde Dehydrogenase Inhibitor, with N-Acetyl-L-Cysteine

Cited by 58 publications

References 14 publications

Induction of Heme Oxygenase 1 by Nitrosative Stress

Induction of Heme Oxygenase 1 by Nitrosative Stress

On the acidity and reactivity of HNO in aqueous solution and biological systems

Studies on the Reaction of Reduced Vitamin B12 Derivatives with the Nitrosyl ­Hydride (HNO) Donor Angeli's Salt: HNO Oxidizes the Transition‐Metal Center of Cob(I)alamin

Contact Info

Product

Resources

About

Studies on the Reaction of Reduced Vitamin B₁₂ Derivatives with the Nitrosyl Hydride (HNO) Donor Angeli's Salt: HNO Oxidizes the Transition‐Metal Center of Cob(I)alamin