Glutathione-S-transferases in lung and sputum specimens, effects of smoking and COPD severity

Harju, Terttu; Mazur, Witold; Merikallio, Heta; Soini, Ylermi; Kinnula, Vuokko L.

doi:10.1186/1465-9921-9-80

Cited by 26 publications

(26 citation statements)

References 32 publications

(39 reference statements)

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“…GSTs are a superfamily of enzymes that catalyze the conjugation of glutathione with electrophilic compounds. They are involved in detoxifying toxic components of tobacco smoke, and the epithelial lining fluid contains 140-fold higher levels of glutathione than plasma, indicating its critical role in protecting airway epithelium from oxidant injury (82,83). In one study, a missense (Met139Ile) coding SNP in GSTT2 was associated with non-small cell lung cancer in smokers (84).…”

Section: Original Researchmentioning

confidence: 99%

Airway Epithelial Expression Quantitative Trait Loci Reveal Genes Underlying Asthma and Other Airway Diseases

Luo

Obeidat

Narzo

et al. 2016

Am J Respir Cell Mol Biol

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Genome-wide association studies (GWASs) have identified loci that are robustly associated with asthma and related phenotypes; however, the molecular mechanisms underlying these associations need to be explored. The most relevant tissues to study the functional consequences of asthma are the airways. We used publically available data to derive expression quantitative trait loci (eQTLs) for human epithelial cells from small and large airways and applied the eQTLs in the interpretation of GWAS results of asthma and related phenotypes. For the small airways (n = 105), we discovered 660 eQTLs at a 10% false discovery rate (FDR), among which 315 eQTLs were not previously reported in a large-scale eQTL study of whole lung tissue. A large fraction of the identified eQTLs is supported by data from Encyclopedia of DNA Elements (ENCODE) showing that the eQTLs reside in regulatory elements (57.5 and 67.6% of cis-and trans-eQTLs, respectively). Published pulmonary GWAS hits were enriched as airway epithelial eQTLs (9.2-fold). Further, genes regulated by asthma GWAS loci in epithelium are significantly enriched in immune response pathways, such as IL-4 signaling (FDR, 5.2 3 10 24 ). The airway epithelial eQTLs described in this study are complementary to previously reported lung eQTLs and represent a powerful resource to link GWAS-associated variants to their regulatory function and thus elucidate the molecular mechanisms underlying asthma and airway-related conditions.

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Section: Original Researchmentioning

confidence: 99%

Airway Epithelial Expression Quantitative Trait Loci Reveal Genes Underlying Asthma and Other Airway Diseases

Luo

Obeidat

Narzo

et al. 2016

Am J Respir Cell Mol Biol

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“…If so, breathprints may reflect the type and activity of the predominant inflammatory pathways, thereby facilitating management of the disease. Since there is evidence that, for instance, oxidative stress responses are markedly different in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I COPD compared with later stages of the disease [17][18][19], the underlying mechanistic profile is likely to depend on GOLD stage. Therefore, noninvasive assessment of exhaled VOCs may also provide new insights into inflammatory pathways in relation to disease stages in COPD.…”

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confidence: 99%

Exhaled air molecular profiling in relation to inflammatory subtype and activity in COPD

Nijs²,

et al. 2011

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Eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) is predictive for responses to inhaled steroids. We hypothesised that the inflammatory subtype in mild and moderate COPD can be assessed by exhaled breath metabolomics.Exhaled compounds were analysed using gas chromatography and mass spectrometry (GC-MS) and electronic nose (eNose) in 28 COPD patients (12/16 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I/II, respectively). Differential cell counts, eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were measured in induced sputum. Relationships between exhaled compounds, eNose breathprints and sputum inflammatory markers were analysed and receiver operating characteristic (ROC) curves were constructed.Exhaled compounds were highly associated with sputum cell counts (eight compounds with eosinophils, 17 with neutrophils; p,0.01). Only one compound (alkylated benzene) overlapped between eosinophilic and neutrophilic profiles. GC-MS and eNose breathprints were associated with markers of inflammatory activity in GOLD stage I (ECP: 19 compounds, p,0.01; eNose breathprint r50.84, p50.002) (MPO: four compounds, p,0.01; eNose r50.72, p50.008). ROC analysis for eNose showed high sensitivity and specificity for inflammatory activity in mild COPD (ECP: area under the curve (AUC) 1.00; MPO: AUC 0.96) but not for moderate COPD.Exhaled molecular profiles are closely associated with the type of inflammatory cell and their activation status in mild and moderate COPD. This suggests that breath analysis may be used for assessment and monitoring of airway inflammation in COPD.

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“…The increased these antioxidant enzymes activities are probably a response to neutralize the impact of increased ROS generation in lung, which provides mainly protection against SMinduced tissue oxidative injury. These results suggest the pivotal role of SOD, CAT and GST for cell adaptation to oxidative stress [12,25].The mechanism of their increasing activities is not quite clear. The expression of the genes such as nuclear factor-kappa B (NF-κB) may stimulate by SM, which leads to increase the expression of these enzymes in lung tissue of patients with OB [26].…”

Section: Discussionmentioning

confidence: 80%

“…The mRNA expressions of Mn-SOD and Cu Zn-SOD were significantly increased in the lungs of SM-exposed patients [27]. SOD, CAT and GST activities may be increased or decreased in various pulmonary diseases including asthma and COPD [6,11,17,25]. Jafari and Ghanei reported a significant increase in SOD and CAT activities in plasma, erythrocytes, and brochoalveolar lavage fluid (BAL) and GST activity in BAL of patients with SM-induced lung injuries [8].…”

Section: Discussionmentioning

confidence: 99%

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The Role of Oxidative Stress in Severity of Obstructive Pulmonary Complications in Sputum of Sulfur Mustard-Injured Patients

Heydari

Jafari

Khazaie

et al. 2017

IJT

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Glutathione-S-transferases in lung and sputum specimens, effects of smoking and COPD severity

Cited by 26 publications

References 32 publications

Airway Epithelial Expression Quantitative Trait Loci Reveal Genes Underlying Asthma and Other Airway Diseases

Airway Epithelial Expression Quantitative Trait Loci Reveal Genes Underlying Asthma and Other Airway Diseases

Exhaled air molecular profiling in relation to inflammatory subtype and activity in COPD

The Role of Oxidative Stress in Severity of Obstructive Pulmonary Complications in Sputum of Sulfur Mustard-Injured Patients

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