Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is now increasing evidence that an oxidant/antioxidant imbalance, in favor of oxidants, occurs in chronic obstructive pulmonary disease (COPD). Evidence is also accumulating that oxidative stress is a critical event in the pathogenesis of this condition. A large number of studies have demonstrated an increased oxidant burden and consequently increased markers of oxidative stress in the airspaces, breath, blood, and urine of smokers and of patients with COPD. There are several events related to oxidative stress, which are important in the pathogenesis of COPD. These include oxidative inactivation of antiproteinases, airspace epithelial injury, increased sequestration of neutrophils in the pulmonary microvasculature, and gene expression of proinflammatory mediators. Oxidative processes have a fundamental role in the inflammation of smokers and patients with COPD, through redox-sensitive transcription factors such as NF-kappaB and AP-1, which regulate the genes for proinflammatory mediators and protective mechanisms, such as antioxidant gene expression. In addition to the oxidative stress produced by cigarette smoking, dietary deficiency in antioxidants is related to the development of airflow limitation, and hence dietary supplementation may be a beneficial therapeutic intervention in this condition. The use of antioxidants with good bioavailability or molecules that have antioxidant enzyme activity may be treatments that not only protect against the direct injurious effects of oxidants, but may fundamentally alter the inflammatory events that are thought to play an important part in the pathogenesis of COPD. MacNee W, Rahman I. Oxidants and antioxidants as therapeutic targets in chronic obstructive pulmonary disease.
 ...
PMID:Oxidants and antioxidants as therapeutic targets in chronic obstructive pulmonary disease. 1055 72

Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants and/or a depletion of antioxidants. Oxidative stress is thought to play an important role in the pathogenesis of a number of lung diseases, not only through direct injurious effects, but by involvement in the molecular mechanisms that control lung inflammation. A number of studies have shown an increased oxidant burden and consequently increased markers of oxidative stress in the airspaces, breath, blood, and urine in smokers and in patients with COPD. The presence of oxidative stress has important consequences for the pathogenesis of COPD. These include oxidative inactivation of antiproteinases, airspace epithelial injury, increased sequestration of neutrophils in the pulmonary microvasculature, and gene expression of proinflammatory mediators. With regard to the latter, oxidative stress has a role in enhancing the inflammation that occurs in smokers and patients with COPD, through the activation of redox-sensitive transcriptions factors such as nuclear factor-kappaB and activator protein-1, which regulate the genes for proinflammatory mediators and protective antioxidant gene expression. The sources of the increased oxidative stress in patients with COPD are derived from the increased burden of oxidants present in cigarette smoke, or from the increased amounts of reactive oxygen species released from leukocytes, both in the airspaces and in the blood. Antioxidant depletion or deficiency in antioxidants may contribute to oxidative stress. The development of airflow limitation is related to dietary deficiency of antioxidants, and hence dietary supplementation may be a beneficial therapeutic intervention in this condition. Antioxidants that have good bioavailability or molecules that have antioxidant enzyme activity may be therapies that not only protect against the direct injurious effects of oxidants, but may fundamentally alter the inflammatory events that play an important part in the pathogenesis of COPD.
 ...
PMID:Oxidants/antioxidants and COPD. 1084 65

There is now considerable evidence for an increased oxidant burden in smokers, particularly in those smokers who develop chronic obstructive pulmonary disease (COPD), as shown by increased markers of oxidative stress in the airspaces, breath, blood and urine. The presence of increased oxidative stress is a critical feature in the pathogenesis of COPD, since it results in inactivation of antiproteinases, airspace epithelial injury, mucus hypersecretion, increased sequestration of neutrophils in the pulmonary microvasculature, and gene expression of pro-inflammatory mediators. The sources of the increased oxidative stress in patients with COPD derive from the increased burden of oxidants present in cigarette smoke, or from the increased amounts of reactive oxygen species released from leukocytes, both in the airspaces and in the blood. Antioxidant depletion or deficiency in antioxidants also contributes to oxidative stress. The development of airflow limitation is related to dietary deficiency of antioxidants and hence dietary supplementation may be a beneficial therapeutic intervention in this condition. Oxidative stress also has a role in enhancing the airspace inflammation, which occurs in smokers and patients with COPD through the activation of redox-sensitive transcriptions factors such as NF-kappa B and AP-1, which regulate the genes for pro-inflammatory mediators and protective antioxidant gene expression. Antioxidants that have good bioavailability or molecules that have antioxidant enzyme activity are therefore therapies that not only protect against the direct injurious effects of oxidants, but also may fundamentally alter the inflammatory events which have a central role in the pathogenesis of COPD.
 ...
PMID:Oxidants/antioxidants and chronic obstructive pulmonary disease: pathogenesis to therapy. 1119 95

Nitric oxide (*NO) and its by-products modulate many physiological functions of skeletal muscle including blood flow, metabolism, glucose uptake, and contractile function. However, growing evidence suggests that an overproduction of nitric oxide contributes to muscle wasting in a number of pathologies including chronic heart failure, sepsis, COPD, muscular dystrophy, and extreme disuse. Limited data point to the potential of inhibition various enzymes by reactive nitrogen species (RNS), including (.)NO and its downstream products such as peroxynitrite, primarily in purified systems. We hypothesized that exposure of skeletal muscle to RNS donors would reduce or downregulate activities of the crucial antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Diaphragm muscle fiber bundles were extracted from 4-month-old Fischer-344 rats and, in a series of experiments, exposed to either (a) 0 (control), 1, or 5 mM diethylamine NONOate (DEANO: *NO donor); (b) 0, 100, 500 microM, or 1 mM sodium nitroprusside (SNP: *NO donor); (c) 0 or 2 mM S-nitroso-acetylpenicillamine (SNAP: *NO donor); or (d) 0 or 500 microM SIN-1 (peroxynitrite donor) for 60 min. DEANO resulted in a 50% reduction in CAT, GPX, and a dose-dependent inhibition of Cu, Zn-SOD. SNP resulted in significantly lower activities for total SOD, Mn-SOD isoform, Cu, Zn-SOD isoform, CAT, and GPX in a dose-dependent fashion. Two millimolar SNAP and 500 microM SIN-1 also resulted in a large and significant inhibition of total SOD and CAT. These data indicate that reactive nitrogen species impair antioxidant enzyme function in an RNS donor-specific and dose-dependent manner and are consistent with the hypothesis that excess RNS production contributes to skeletal muscle oxidative stress and muscle dysfunction.
 ...
PMID:Specificity of antioxidant enzyme inhibition in skeletal muscle to reactive nitrogen species donors. 1207 89

Chronic obstructive pulmonary disease (COPD) is highly prevalent and its pathogenesis is still not completely clarified. Clinically stable patients (n=21) and healthy subjects (n=24) were studied for blood markers of oxidative injury and antioxidant status. The plasma concentration of protein carbonyls was significantly increased in COPD patients, both ex-smokers (0.76 +/- 0.28 nmol mg(-1)) and smokers (0.99 +/- 020 nmol mg(-1)) versus controls (0.49 +/- 0.14 nmol mg(-1)) . The concentration of total thiols was slightly enhanced in plasma of the COPD patients (ex-smokers 492 +/- 23 micromol 1(-1) and smokers 505 +/- 36 micromol 1(-1) versus controls 450 +/- 67 micromol 1(-1); p < 0.05). The activity of the antioxidant enzyme superoxide dismutase was increased in erythrocytes (activity in U g(-1) haemoglobin; ex-smokers 4460 +/- 763 and smokers 4114+/- 1060 versus 3015 +/- 851 in controls; p > 0.01), while glutathione peroxidase activity was decreased in total blood (activity in U g(-1) haemoglobin: ex-smokers 27 +/- 9 and smokers 23 +/- 9 versus 47 +/- 25; p < 0.01). Lower levels of selenium in plasma were also found for COPD patients (concentration in mg 1(-1): ex-smokers 0.030 +/- 0.019 and smokers 0.032 +/- 0.024 versus 0.058 +/- 0.023 in controls; p < 0.01), being more evident in those with very low levels of arterial oxygen pressure. In addition, the levels of potassium and rubidium were increased in blood cells of the patient group. All these changes might reflect oxidant damage and an altered electrolytic homeostasis, and can be interpreted as markers of COPD rather than as indicators of smoking habits.
 ...
PMID:Systemic markers of the redox balance in chronic obstructive pulmonary disease. 1584 66

The goal of this study was to evaluate the role of oxidant-antioxidant balance in the pathogenesis of COPD. We included 30 healthy nonsmokers [24 male, 6 female; mean age (yr) +/- SD: 62.4 +/- 9.3], 30 healthy smokers [27 male, 3 female; mean age (yr) +/- SD: 58.7 +/- 6.0], 71 patients with stable COPD [68 male, 3 female; mean age (yr) +/- SD: 63.5 +/- 7.9], and 31 patients with COPD exacerbation [30 male, 1 female; mean age (yr) +/- SD: 64.2 +/- 7.3]. In all study groups the peripheral venous blood samples were taken for plasma malonyldialdehyde (MDA), a parameter of lipid peroxidation caused by the oxidants, and erythrocyte superoxide dismutase (SOD), an antioxidant enzyme. The mean plasma MDA level was higher in healthy smokers and in patients with COPD than in healthy nonsmokers (p < 0.05), and erythrocyte SOD enzyme activity in patients with COPD exacerbation (1048.2 +/- 226.5 Ug/Hb) was significantly higher than in healthy nonsmokers (947.9 +/- 198.0 Ug/Hb) (p < 0.05). Although mean erythrocyte SOD enzyme activity in healthy smokers and patients with stable COPD was higher than in healthy nonsmokers, the difference was not statistically significant. We found that healthy smokers and stable and exacerbated COPD patients had an impairment in oxidant-antioxidant balance. We suggested that new therapeutic interventions, which may repair the impaired oxidant-antioxidant balance in COPD, are needed to prevent the development of COPD.
 ...
PMID:Oxidant-antioxidant balance in patients with COPD. 1662 73

Inhaled corticosteroids (ICS) are the standard of care in asthma and are widely used in the treatment of patients with COPD. The influence of steroids on inflammatory processes has long been established since glucocorticoids and their receptor belong to the regulatory network involved in inhibition of several inflammatory pathways. Inflammatory processes are usually accompanied by an increased oxidative burden followed by a depletion of antioxidants. Therefore, the effects of steroids on antioxidant status have been investigated revealing possible positive effects on the reduced antioxidant enzyme activity. Nevertheless, the mechanisms of this modulation have not been fully elucidated yet. It is possible that antioxidant enzyme activity is regulated at the level of transcription. Additionally, because of the fact that antioxidant enzymes are trace element dependent, steroids may affect their activity through influence on trace element accumulation. This review summarizes the effects of steroids on the antioxidant enzymes activity in vitro and in vivo in relation to asthma and COPD.
 ...
PMID:Glucocorticosteroids as antioxidants in treatment of asthma and COPD. New application for an old medication? 1714 70

Oxidative stress is thought to play a major role in the pathogenesis of chronic obstructive pulmonary disease, characterized by impaired lung function. A large number (> or =33) of GT repeats (L-allele) in the gene of the powerful antioxidant enzyme heme oxygenase-1 has been associated with susceptibility to accelerated lung function decline. In contrast, beta-carotene may help to protect against accelerated decline. To determine whether high serum levels of beta-carotene might counterbalance the greater susceptibility of L-allele carriers, the authors analyzed the annual decline in forced expiratory volume in 1 second (FEV1) in a general population sample of 523 French subjects (20-44 years, 50% men) examined in 1992 and 2000 as part of the European Community Respiratory Health Survey. Analysis of covariance, adjusted for sex as well as baseline age, body mass index, smoking, and FEV1, showed that, among subjects with low beta-carotene levels, L-allele carriers experienced a steeper mean FEV1 decline than did noncarriers (mean = -58.8, 95% confidence interval: -73.2, -44.5 vs. mean = -34.7, 95% confidence interval: -38.9, -29.8 ml/year) (p = 0.009), whereas among subjects with high beta-carotene levels, the FEV1 decline was not different in L-allele carriers and noncarriers (two-sided p = 0.9). The results suggest that high levels of beta-carotene might counterbalance the effects on FEV1 decline of a genetically determined deficiency in antioxidant response.
 ...
PMID:Interaction between a heme oxygenase-1 gene promoter polymorphism and serum beta-carotene levels on 8-year lung function decline in a general population: the European Community Respiratory Health Survey (France). 1797 38

Chronic obstructive pulmonary disease (COPD) is a global health problem. Being a progressive disease characterized by inflammation and predominantly caused by tobacco smoking, it deteriorates pulmonary and skeletal muscle functioning, and reduces physical behavior, societal participation and quality of life. During the last two decades studies were focused on the airway and systemic inflammation, oxidative stress, and airway and/or parenchymal remodeling. Macrophages, neutrophils and T cells are thought to be important key players, as well as structural cells like fibroblasts, epithelial, endothelial and smooth muscle cells. Mediators and proteins including cytokines, chemokines, growth factors, proteinases, and oxidants seem to be involved differentially in its pathogenesis. Current pharmacological treatments are directed to reducing airway inflammation, boosting the endogenous levels of anti-oxidants and relieving airway contraction and sputum production. Most agents were primarily used for treating asthma. But in contrast to asthma, these treatments are not very effective in COPD. As a result, novel more specifically acting interventional drugs with less side effects are being developed to treat chronic inflammatory diseases, including COPD. This review highlights studies on novel or potential drug antioxidants such as dietary antioxidants supplementation, N-acetyl-L-cysteine, N-acystelyn, endosteine, antioxidant enzyme mimetics, and anti-inflammatory agents like antagonists of cytokines, such as tumor necrosis factor (TNF)-alpha, CXCL8, and CCL2, and inhibitors of signal transduction proteins including phosphodiesterase 4, MAPK p38, P1-3k, and NFkappaB.
 ...
PMID:Future therapeutic treatment of COPD: struggle between oxidants and cytokines. 1822 60

Chronic oxidative stress and systemic inflammation contribute to the pathology of several chronic diseases, one among which is chronic obstructive pulmonary disease (COPD). In addition, increased oxidative stress and inflammation have been observed to be negatively associated with telomere length (TL). Our aim was to investigate the TL in COPD patients in relation to pulmonary and extrapulmonary disease severity. Furthermore, based on experimental evidence suggesting the effects of oxidative stress on telomere shortening, we studied the association of TL with the antioxidant enzyme superoxide dismutase (SOD). One hundred and two COPD patients with moderate to severe COPD were studied and compared with 19 healthy age-matched controls. Patients were characterized by elevated levels of inflammatory markers (CRP, sTNF-receptors) and lower SOD-activity than the controls (p<0.001), irrespective of the SOD genotype. TL was negatively associated with age (p<0.01) and was significantly shorter in COPD patients than controls (p<0.05). Within the patient group age-adjusted TL variability could not be explained by lung function and smoking history but a modest association was found with the percentage of fat mass (p<0.05). These data provide evidence for a relationship between a disturbed oxidant/antioxidant balance and telomere shortening and indicate that preservation of fat mass may be protective in delaying telomere shortening in COPD patients.
 ...
PMID:Telomere shortening in chronic obstructive pulmonary disease. 1894 4


1 2 3 Next >>