Peroxynitrite Elevation in Exhaled Breath Condensate of COPD and Its Inhibition by Fudosteine

Osoata, Grace O.; Hanazawa, Toyoyuki; Brindicci, Caterina; Ito, Misako; Barnes, Peter J.; Kharitonov, Sergei A.; Ito, Kazuhiro

doi:10.1378/chest.08-2105

Cited by 78 publications

(46 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As discussed earlier, oxidative stress activates NF-κB, thus increasing inflammation. Superoxide anions interact with nitric oxide to form peroxynitrite which is increased in the lungs of COPD patients [40]. This leads to nitration of particular tyrosine residues on histone deacetylase-2 (HDAC2), resulting in its activation and degradation [41].…”

Section: Figurementioning

confidence: 99%

Mechanisms of development of multimorbidity in the elderly

2015

Self Cite

View full text Add to dashboard Cite

In ageing populations many patients have multiple diseases characterised by acceleration of the normal ageing process. Better understanding of the signalling pathways and cellular events involved in ageing shows that these are characteristic of many chronic degenerative diseases, such as chronic obstructive pulmonary disease (COPD), chronic cardiovascular and metabolic diseases, and neurodegeneration. Common mechanisms have now been identified in these diseases, which show evidence of cellular senescence with telomere shortening, activation of PI3K-AKT-mTOR signalling, impaired autophagy, mitochondrial dysfunction, stem cell exhaustion, epigenetic changes, abnormal microRNA profiles, immunosenescence and low grade chronic inflammation ("inflammaging"). Many of these pathways are driven by chronic oxidative stress. There is also a reduction in anti-ageing molecules, such as sirtuins and Klotho, which further accelerates the ageing process. Understanding these molecular mechanisms has identified several novel therapeutic targets and several drugs have already been developed that may slow the ageing process, as well as lifestyle interventions, such as diet and physical activity. This indicates that in the future new treatment approaches may target the common pathways involved in multimorbidity and this area of research should be given high priority. Thus, COPD should be considered as a component of multimorbidity and common disease pathways, particularly accelerated ageing, should be targeted. @ERSpublications Multimorbidities share many common underlying mechanisms that may be linked to common causes such as oxidative stress

show abstract

Section: Figurementioning

confidence: 99%

Mechanisms of development of multimorbidity in the elderly

2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…Currently, 3-nitrotyrosine is measured as a footprint of peroxynitrite release. Using a new noninvasive technique, Osoata et al were able to measure peroxynitrite in exhaled breath condensate [38]. The levels of peroxynitrite were significantly higher in patients with COPD compared with smokers and healthy controls [38].…”

Section: Oxidative/nitrative Stress In Obstructive Airway Diseasesmentioning

confidence: 99%

Role of the nitric oxide–soluble guanylyl cyclase pathway in obstructive airway diseases

Dupont

Glynos²,

Bracke

et al. 2014

Pulmonary Pharmacology & Therapeutics

View full text Add to dashboard Cite

a b s t r a c tNitric oxide (NO) is a gaseotransmitter, which is involved in many signaling processes in health and disease. Three enzymes generate NO from L-arginine, with citrulline formed as a by-product: neuronal NO synthase (nNOS or NOS1), endothelial NOS (eNOS or NOS3) and inducible NOS (iNOS or NOS2). NO is a ligand of soluble guanylyl cyclase (sGC), an intracellular heterodimer enzyme that catalyzes the conversion of guanosine triphosphate (GTP) to cyclic GMP (cGMP). cGMP further activates protein kinase G that eventually reduces the smooth muscle tone in bronchi or vessels. Phosphodiesterase 5 (PDE 5 ) degrades cGMP to GMP. However, NO reacts with superoxide anion (O À 2 ), leading to formation of the proinflammatory molecule peroxynitrite.Under physiological conditions, NO plays a homeostatic bronchoprotective role in healthy subjects. In obstructive airway diseases, NO can be beneficial by its bronchodilating effect, but could also be detrimental by the formation of peroxynitrite. Since asthma and COPD are associated with increased levels of exhaled NO, chronic inflammation and increased airway smooth muscle tone, the NO/sGC/cGMP pathway could be involved in these highly prevalent obstructive airway diseases. Here we review the involvement of NO, NO synthases, guanylyl cyclases, cGMP and phophodiesterase-5 in asthma and COPD and potential therapeutic approaches to modulate this pathway.

show abstract

“…Elevated rates of tissue peroxynitrite production are associated with a number of respiratory diseases including COPD (Ichinose et al, 2000). Peroxynitrite generation is significantly elevated in sputum macrophages of COPD patients, which is negatively correlated with pulmonary function in these patients (Osoata et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Asymmetric dimethyl-arginine metabolism in a murine model of cigarette smoke-mediated lung inflammation

Staab

Weigel

Xiao

et al. 2014

Journal of Immunotoxicology

View full text Add to dashboard Cite

There is increasing evidence that the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethyl-arginine (ADMA) is involved in the pathogenesis of chronic lung diseases. One important regulator of this molecule is the ADMA-metabolizing enzyme dimethyl-arginine dimethyl-aminohydrolase (DDAH). The objective of this study was to determine whether perturbation of the ADMA-DDAH pathway contributes to lung inflammation following exposure to cigarette smoke (CS). For these studies, wild-type and DDAH transgenic mice were sham or CS-exposed. Serum ADMA levels were determined by mass spectrometry. ADMA content and DDAH expression were also visualized in mouse lung tissue by immunohistochemistry. DDAH expression was determined by real-time quantitative PCR (qPCR). Inflammation was assessed by H&E staining and analyses of total cell counts and fluid tumor necrosis factor (TNF)-levels (using ELISA) in lung lavage fluid. NF-B binding activity in mouse lung epithelial (LA-4) cells was assessed by a transcription factor-binding assay. The results indicated that the concentration of serum ADMA was increased following exposure to CS, and this corresponded with increased ADMA content in bronchial epithelial cells in lung tissue. Total lung DDAH expression was significantly decreased in lung tissue and cultured LA-4 cells following CS exposure. Addition of exogenous ADMA increased CSE-mediated NF-B binding activity and TNFa production in LA-4 cells more than 2-fold compared to that in CSE-exposed controls. CS-mediated lung inflammation was significantly attenuated in DDAH transgenic mice compared to in wild-type controls. These findings demonstrated that lung ADMA metabolism was altered in mice following CS exposure and suggested that ADMA played a role in CS-mediated inflammation through increasing the presence of inflammatory mediators in lung epithelial cells.

show abstract

Peroxynitrite Elevation in Exhaled Breath Condensate of COPD and Its Inhibition by Fudosteine

Cited by 78 publications

References 37 publications

Mechanisms of development of multimorbidity in the elderly

Mechanisms of development of multimorbidity in the elderly

Role of the nitric oxide–soluble guanylyl cyclase pathway in obstructive airway diseases

Asymmetric dimethyl-arginine metabolism in a murine model of cigarette smoke-mediated lung inflammation

Contact Info

Product

Resources

About