Protection from Experimental Asthma by an Endogenous Bronchodilator

Que, Loretta G.; Liu, Limin; Yun, Yan; Whitehead, Gregory S.; Gavett, Stephen H.; Schwartz, David A.; Stamler, Jonathan S.

doi:10.1126/science.1108228

Cited by 262 publications

(275 citation statements)

References 24 publications

Supporting

Mentioning

256

Contrasting

Unclassified

Order By: Relevance

“…An enzymatic reductase that uses NADH but not NADPH as a source of electrons was observed in BAEC cell lysate with a K m of 7 M. Previous studies have identified glutathione-dependent formaldehyde dehydrogenase (alcohol dehydrogenase class III) as a catalyst of NADH-dependent GSNO reduction with a K m of 28 M (28). Mice lacking this enzyme had increased RSNO levels in the lungs and were protected from experimental asthma (33). Whatever the nature of the catalyst, it is clear that this activity is robust enough to consume intracellular GSH in the face of high intracellular L-CysNO levels.…”

Section: Discussionmentioning

confidence: 99%

Requirement of Transmembrane Transport for S-Nitrosocysteine-dependent Modification of Intracellular Thiols

Broniowska

Zhang

Hogg

2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

S-Nitrosothiols have been implicated as intermediary transducers of nitric oxide bioactivity; however, the mechanisms by which these compounds affect cellular functions have not been fully established. In this study, we have examined the effect of S-nitrosothiol transport on intracellular thiol status and upon the activity of a target protein (caspase-3), in bovine aortic endothelial cells. We have previously demonstrated that the specific transport of amino acid-based S-nitrosothiols (S-nitroso-L-cysteine and S-nitrosohomocysteine) occurs via amino acid transport system L to generate high levels of intracellular protein S-nitrosothiols (Zhang, Y., and Hogg, N. (2004) Proc. Natl. Acad. Sci. U. S. A. 101, 7891-7896). In this study, we demonstrate that the transport of S-nitrosothiols is essential for these compounds to affect intracellular thiol levels and to modify intracellular protein activity. Importantly, the ability of these compounds to affect intracellular processes occurs independently of nitric oxide formation. These findings suggest that the major action of these compounds is not to liberate nitric oxide in the extracellular space but to be specifically transported into cells where they are able to modify cellular functions through nitric oxide-independent mechanisms. S-Nitrosothiols (RSNO),2 thioesters of nitrite, have been implicated to play a role in the complex biological responses of nitric oxide (NO). S-Nitrosation has been observed in whole animals and in the cell systems under basal (1-3) and inflammatory conditions (4, 5). It has been suggested that S-nitrosation of enzyme cysteine residues represents a post-translation modification involved in signal transduction and the alteration of enzyme function in a similar way to phosphorylation (6). Indeed, there are numbers of protein targets that have been reported to be nitrosated on cysteine residues including p21ras (7), L-type Ca 2ϩ channels (8), transcription factor NF-B (9), inhibitory B kinase (10), and caspase-3 (11, 12).Although the evidence is strong, in test systems, that thiol nitrosation can affect many cellular processes and enzyme activities, it is less clear that this represents a physiological or a pathophysiological effect of NO formation. NO per se is a poor and inefficient nitrosating agent (13), and intracellular systems that catalyze nitrosation from NO have not yet been defined. Although the plasma copper-protein ceruloplasmin has been shown to catalyze RSNO formation (14), this has not been demonstrated in whole blood containing high concentrations of hemoglobin, a potent NO scavenger (15). From a pharmacological perspective, however, it has been demonstrated in many studies that the exposure of cells to low molecular weight RSNOs, such as S-nitrosoglutathione (GSNO), S-nitroso-N-acetylpenicillamine (SNAP), and S-nitroso-L-cysteine (L-CysNO), can affect cellular processes (16). Although it is often assumed that these compounds spontaneously release NO in cell culture and that the effects of these compounds can be attributed t...

show abstract

Section: Discussionmentioning

confidence: 99%

Requirement of Transmembrane Transport for S-Nitrosocysteine-dependent Modification of Intracellular Thiols

Broniowska

Zhang

Hogg

2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…NOS enzyme) [18], IV) reversibility; and V) enzymatic control (e.g. S-nitrosoglutathione; SNO) reductase ( [1,19]) controls S-nitrosothiol tone [9,20]). In addition, dysregulation of protein S-nitrosylation is associated with a growing list of diseases, including cystic fibrosis, asthma, heart disease, and neurodegenerative diseases.…”

Section: Oxidants As Modulators Of Signal Transductionmentioning

confidence: 99%

“…Intriguingly, the activity of GSNO reductase had been demonstrated to by upregulated in a mouse model of asthma, mediating decreases in lung S-nitrosothiol levels, and increases in airway hyperresponsiveness (AHR), a cardinal feature of asthma. GSNO reductase knock-out mice had elevated levels of lung S-nitrosothiols, which act as endogenous bronchodilators and protected against increases in AHR or tachyphylaxis [20]. GSNO reductase knock-out mice were also hypotensive under anesthesia and showed enhanced susceptibility to mortality from endotoxin or septic shock [9].…”

Section: Biochemical and Genetic Regulation Of Reversible Cysteine Oxmentioning

confidence: 99%

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

Janssen–Heininger¹,

Mossman²,

Heintz³

et al. 2008

Free Radical Biology and Medicine

Self Cite

688

652

View full text Add to dashboard Cite

“…SNP at 500 nM has been shown to effectively disperse various single species biofilms as well as multispecies biofilms, including those in CF sputum [22, 23, 53]. S-nitrosoglutathione (GSNO), a naturally occurring S-nitrosothiol, is also used clinically as a vasodilator, including in the lungs of CF patients [130,131]. An important and highly versatile class of NO donors are the diazeniumdiolates (NONOates).…”

mentioning

confidence: 99%

Nitric Oxide: A Key Mediator of Biofilm Dispersal with Applications in Infectious Diseases

Barraud¹,

Kelso²,

Rice

et al. 2014

CPD

206

196

View full text Add to dashboard Cite

Studies of the biofilm life cycle can identify novel targets and strategies for improving biofilm control measures. Of particular interest are dispersal events, where a subpopulation of cells is released from the biofilm community to search out and colonize new surfaces. Recently, the simple gas and ubiquitous biological signaling molecule nitric oxide (NO) was identified as a key mediator of biofilm dispersal conserved across microbial species. Here, we review the role and mechanisms of NO mediating dispersal in bacterial biofilms, and its potential for novel therapeutics. In contrast to previous attempts using high dose NO aimed at killing pathogens, the use of low, non-toxic NO signals (picomolar to nanomolar range) to disperse biofilms represents an innovative and highly favourable approach to improve infectious disease treatments. Further, several NO-based technologies have been developed that offer a versatile range of solutions to control biofilms, including: (i) NO-generating compounds with short or long half-lives and safe or inert residues, (ii) novel compounds for the targeted delivery of NO to infectious biofilms during systemic treatments, and (iii) novel NO-releasing materials and surface coatings for the prevention and dispersal of biofilms. Overall the use of low levels of NO exploiting its signaling properties to induce dispersal represents an unprecedented and promising strategy for the control of biofilms in clinical and industrial contexts. AbstractStudies of the biofilm life cycle can identify novel targets and strategies for improving biofilm control measures. Of particular interest are dispersal events, where a subpopulation of cells is released from the biofilm community to search out and colonize new surfaces. Recently, the simple gas and ubiquitous biological signaling molecule nitric oxide (NO) was identified as a key mediator of biofilm dispersal conserved across microbial species. Here, we review the role and mechanisms of NO mediating dispersal in bacterial biofilms, and its potential for novel therapeutics. In contrast to previous attempts using high dose NO aimed at killing pathogens, the use of low, non-toxic NO signals (picomolar to nanomolar range) to disperse biofilms represents an innovative and highly favourable approach to improve infectious disease treatments. Further, several NO-based technologies have been developed that offer a versatile range of solutions to control biofilms, including: (i) NO-generating compounds with short or long half-lives and safe or inert residues, (ii) novel compounds for the targeted delivery of NO to infectious biofilms during systemic treatments, and (iii) novel NO-releasing materials and surface coatings for the prevention and dispersal of biofilms. Overall the use of low levels of NO exploiting its signaling properties to induce dispersal represents an unprecedented and promising strategy for the control of biofilms in clinical and industrial contexts. 3 Increased antimicrobial tolerance in biofilms is the basis for chronic infecti...

show abstract

Protection from Experimental Asthma by an Endogenous Bronchodilator

Cited by 262 publications

References 24 publications

Requirement of Transmembrane Transport for S-Nitrosocysteine-dependent Modification of Intracellular Thiols

Requirement of Transmembrane Transport for S-Nitrosocysteine-dependent Modification of Intracellular Thiols

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

Nitric Oxide: A Key Mediator of Biofilm Dispersal with Applications in Infectious Diseases

Contact Info

Product

Resources

About