Serum Derivatives of Reactive Oxygen Metabolites are Associated with Severity of Chronic Obstructive Pulmonary Disease and Affected by a p53 Gene Polymorphism

Yamamura, Koichi; Nojiri, Masafumi; Nishiki, Kazuaki; Kato, Ryo; Shinomiya, Shohei; Takahara, Yutaka; Oikawa, Taku; Ishizaki, Takeshi; Toga, Hirohisa; Mizuno, Shiro

doi:10.2147/copd.s366792

Cited by 3 publications

(1 citation statement)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8 In patients with COPD, large amounts of free radicals are generated by cigarette smoking, which cause oxidative stress, thereby ATM-regulated p53 pathway is activated, inhibiting cell cycle and inducing apoptosis. 9 Studies have found that p53 is pivotal in the prevention of emphysema and is associated with acute lung injury (ALI), COPD, pulmonary hypertension, and other respiratory diseases. 10 p53 attenuates ALI by negatively regulating LPS-induced NF-κB activity.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway

Cai,

Chen,

Zhu

et al. 2023

COPD

View full text Add to dashboard Cite

Background: Chronic obstructive pulmonary disease (COPD) is a persistent chronic bronchitis disease, and its potential biomarkers have not been fully expounded. This study aims to explore the role of Guanine nucleotide binding protein like-3-like (GNL3L) in COPD induced by cigarette smoking (CS) in vivo. Methods: Two microarray datasets of COPD were selected to screen differentially expressed genes (DEGs). A protein-protein interaction network was constructed to find hub genes. The COPD model was conducted using CS/LPS-induced mouse and cigarette smoke extract induced human bronchial epithelial cells. The pathological changes of lung tissue in mice were observed by hematoxylin-eosin staining and mean linear intercept. Cell viability was measured by CCK8 assay. Oxidative stress-related indicators, inflammatory factors, and ATM/p53 related-proteins were assessed using ELISA and Western blot. Results: In this study, there were 110 common DEGs identified from the two datasets (GSE5058 and GSE38974). The key gene GNL3L was the optimal indicator to distinguish between samples with COPD and healthy controls. Through the in vivo and in vitro experiments, GNL3L knockdown significantly improved the pathological features of CS/LPS-induced COPD mice, promoted cell viability, inhibited inflammation (IL-1β, IL-8, and TNF-α), oxidative stress (MDA, SOD, and CAT), and ATM/p53 related-proteins (ATM, p53, and p21). Conclusion: GNL3L is a novel biomarker of COPD, and knockdown of GNL3L participates in the progression of COPD by inhibiting ATM/p53 pathway.

show abstract

Section: Introductionmentioning

confidence: 99%

Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway

Cai,

Chen,

Zhu

et al. 2023

COPD

View full text Add to dashboard Cite

show abstract

A titratable murine model of progressive emphysema using tracheal porcine pancreatic elastase

Joshi,

Devine,

Joshi

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Progressive emphysema often leads to end-stage lung disease. Most mouse models of emphysema are typically modest (i.e. cigarette smoke exposure), and changes over time are difficult to quantify. The tracheal porcine pancreatic elastase model (PPE) produces severe injury, but the literature is conflicted as to whether emphysema improves, is stable, or progresses over time. We hypothesized a threshold of injury below which repair would occur and above which emphysema would be stable or progress. We treated 8-week-old C57BL6 mixed sex mice with 0, 0.5, 2, or 4 activity units of PPE in 100 µL PBS and performed lung stereology at 21 and 84 days. There were no significant differences in weight gain or mouse health. Despite minimal emphysema at 21-days in the 0.5 units group (2.8 µm increased mean linear intercept, MLI), MLI increased by 4.6 µm between days 21 and 84 (p = 0.0007). In addition to larger MLI at 21 days in 2- and 4-unit groups, MLI increases from day 21 to 84 were 17.2 and 34 µm respectively (p = 0.002 and p = 0.0001). Total lung volume increased, and alveolar surface area decreased with time and injury severity. Contrary to our hypothesis, we found no evidence of alveolar repair over time. Airspace destruction was both progressive and accelerative. Future mechanistic studies in lung immunity, mechano-biology, senescence, and cell-specific changes may lead to novel therapies to slow or halt progressive emphysema in humans.

show abstract

Serum Derivatives–Reactive Oxygen Metabolite Levels as a Marker of Clinical Conditions in Patients with Bronchial Asthma, COPD, or Asthma–COPD Overlap: A Prospective Study

Nakamoto,

Watanabe,

Saito

et al. 2024

JCM

View full text Add to dashboard Cite

Background: Oxidative stress plays an important role in the pathophysiology of bronchial asthma (BA), chronic obstructive pulmonary disease (COPD), and asthma–COPD overlap (ACO), but its relevance has not been fully elucidated. The aim of this study was to measure the levels of oxidative stress and investigate its clinical significance in patients with BA, COPD, or ACO. Methods: We recruited 214 patients between June 2020 and May 2023 (109 patients with BA, 63 with COPD, and 42 with ACO). To assess clinical conditions, we evaluated patient characteristics, results of respiratory function tests and blood tests, and administered several questionnaires. We evaluated oxidative stress using the test for derivatives–reactive oxygen metabolites (d–ROMs) in serum. Results: The d–ROMs levels were significantly higher in patients with COPD or ACO than in patients with BA. There was no difference in serum d–ROMs levels between the COPD and ACO groups. In BA, d–ROMs levels were positively correlated with interleukin (IL)-6, IL-8, serum amyloid A (SAA), and C-reactive protein (CRP) levels; white blood cell (WBC) and neutrophil counts; and St. George’s Respiratory Questionnaire (SGRQ) scores, and they were negatively correlated with forced expiratory volume in 1 s (%FEV1) and asthma control test (ACT) score. In COPD, d–ROMs levels were positively correlated with IL-6, SAA, and CRP levels; WBC, neutrophil, and eosinophil counts; and COPD assessment test (CAT) and SGRQ scores, and they were negatively correlated with forced vital capacity (%FVC), %FEV1, and %FEV1/FVC scores. In ACO, d–ROMs levels were positively correlated with IL-6, SAA, tumor necrosis factor alpha (TNF-α), and CRP levels; and CAT and SGRQ scores, and they were negatively correlated with %FVC and %FEV1 scores. Conclusions: Serum d–ROMs levels may serve as a marker reflecting clinical conditions such as systemic inflammation, symptom severity, and airflow limitation in patients with BA, COPD, and ACO.

show abstract

Serum Derivatives of Reactive Oxygen Metabolites are Associated with Severity of Chronic Obstructive Pulmonary Disease and Affected by a p53 Gene Polymorphism

Cited by 3 publications

References 43 publications

Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway

Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway

A titratable murine model of progressive emphysema using tracheal porcine pancreatic elastase

Serum Derivatives–Reactive Oxygen Metabolite Levels as a Marker of Clinical Conditions in Patients with Bronchial Asthma, COPD, or Asthma–COPD Overlap: A Prospective Study

Contact Info

Product

Resources

About