scholarly journals LncRNA Nqo1-AS1 Attenuates Cigarette Smoke-Induced Oxidative Stress by Upregulating its Natural Antisense Transcript Nqo1

2021 ◽  
Vol 12 ◽  
Author(s):  
Haiyun Zhang ◽  
Ruijuan Guan ◽  
Zili Zhang ◽  
Defu Li ◽  
Jingyi Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoke ◽  
Mrna Stability ◽  
Molecular Mechanisms ◽  
Antisense Transcript ◽  
Alveolar Epithelium ◽  
Chronic Obstructive ◽  
Protein Coding ◽  
Obstructive Pulmonary Disease ◽  
Coding Potential

Evidence of the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of chronic obstructive pulmonary disease (COPD) is growing but still largely unknown. This study aims to explore the expression, functions and molecular mechanisms of Fantom3_F830212L20, a lncRNA that transcribes in an antisense orientation to Nqo1.We name this lncRNA as Nqo1 antisense transcript 1 (Nqo1-AS1). The distribution, expression level and protein coding potential of Nqo1-AS1 were determined. The effects of Nqo1-AS1 on cigarette smoke (CS)-induced oxidative stress were also evaluated. The results showed that Nqo1-AS1 were mainly located in the cytoplasm of mouse alveolar epithelium and had a very low protein coding potential. Nqo1-AS1 (or its human homologue) was increased with the increase of CS exposure. Nqo1-AS1 overexpression enhanced the mRNA and protein levels of Nqo1 and Serpina1 mRNA expression, and attenuated CS-induced oxidative stress, whereas knockdown of Nqo1-AS1 significantly decreased Nqo1 and Serpina1 mRNA expressions, and aggravated CS-induced oxidative stress. Nqo1-AS1 increased Nqo1 mRNA stability and upregulated Nqo1 expression through antisense pairing with Nqo1 3′UTR. In conclusion, these results suggest that Nqo1-AS1 attenuates CS-induced oxidative stress by increasing Nqo1 mRNA stability and upregulating Nqo1 expression, which might serve as a novel approach for the treatment of COPD.

scholarly journals Cigarette smoke-induced emphysema in A/J mice is associated with pulmonary oxidative stress, apoptosis of lung cells, and global alterations in gene expression

2009 ◽  
Vol 296 (6) ◽  
pp. L888-L900 ◽  
Author(s):  
Tirumalai Rangasamy ◽  
Vikas Misra ◽  
Lijie Zhen ◽  
Clarke G. Tankersley ◽  
Rubin M. Tuder ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Phase I ◽  
Cigarette Smoke ◽  
Phase Ii ◽  
Pulmonary Emphysema ◽  
Molecular Mechanisms ◽  
The United States ◽  
Phase Iii ◽  
Chronic Obstructive

Cigarette smoking is the major risk factor for developing chronic obstructive pulmonary disease, the fourth leading cause of deaths in the United States. Despite recent advances, the molecular mechanisms involved in the initiation and progression of this disease remain elusive. We used Affymetrix Gene Chip arrays to determine the temporal alterations in global gene expression during the progression of pulmonary emphysema in A/J mice. Chronic cigarette smoke (CS) exposure caused pulmonary emphysema in A/J mice, which was associated with pronounced bronchoalveolar inflammation, enhanced oxidative stress, and increased apoptosis of alveolar septal cells. Microarray analysis revealed the upregulation of 1,190, 715, 260, and 246 genes and the downregulation of 1,840, 730, 442, and 236 genes in the lungs of mice exposed to CS for 5 h, 8 days, and 1.5 and 6 mo, respectively. Most of the genes belong to the functional categories of phase I genes, Nrf2-regulated antioxidant and phase II genes, phase III detoxification genes, and others including immune/inflammatory response genes. Induction of the genes encoding multiple phase I enzymes was markedly higher in the emphysematous lungs, whereas reduced expression of various cytoprotective genes constituting ubiquitin-proteasome complex, cell survival pathways, solute carriers and transporters, transcription factors, and Nrf2-regulated antioxidant and phase II-responsive genes was noted. Our data indicate that the progression of CS-induced emphysema is associated with a steady decline in the expression of various genes involved in multiple pathways in the lungs of A/J mice. Many of the genes discovered in this study could rationally play an important role in the susceptibility to CS-induced emphysema.

Chrysene accelerates the proceeding of chronic obstructive pulmonary disease with the aggravation of inflammation and apoptosis in cigarette smoke exposed mice

2020 ◽  
pp. 096032712097934
Author(s):  
Yuan Gao ◽  
Xinjia Zhou ◽  
Yan Zhou ◽  
Wei Zhang ◽  
Li Zhao
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Cigarette Smoke ◽  
Molecular Mechanisms ◽  
Smooth Muscle Actin ◽  
Lavage Fluid ◽  
Living Environment ◽  
Chronic Obstructive ◽  
High Morbidity ◽  
Obstructive Pulmonary Disease

Chrysene, one of the basic polycyclic aromatic hydrocarbons (PAHs), has been reported to make damages to human health and living environment. Chronic obstructive pulmonary disease (COPD) is a progressive disorder with high morbidity and mortality. To investigate the role of chrysene in the development of COPD, male C57BL/6 mice were exposed to the cigarette smoke (CS) followed with the administration of chrysene. Morphological analyses indicated that chrysene caused earlier and severer pathological changes in CS-exposed mice. Besides, CS-exposed mice with chrysene treatment showed obvious collagen deposition, elevated α-smooth muscle actin (α-SMA) expression and reduced E-cadherin abundance at earlier stage, which suggested the acceleration and aggravation of pulmonary fibrosis. Moreover, quantification of leukocytes and pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and lung tissues implied that chrysene significantly exacerbated the proceeding of inflammation in CS-exposed mice. Furthermore, significantly increased apoptotic rates, augmented expressions of apoptotic related proteins and highly expressed TRPV1 were determined in CS-exposed mice with chrysene treatment, which indicated the association between COPD pathogenesis and TRPV1 channel. In summary, our findings elucidate that chrysene accelerates the development of COPD in a murine model with new molecular mechanisms.

scholarly journals Loading of Beclomethasone in Liposomes and Hyalurosomes Improved with Mucin as Effective Approach to Counteract the Oxidative Stress Generated by Cigarette Smoke Extract

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 850
Author(s):  
Maria Letizia Manca ◽  
Maria Ferraro ◽  
Elisabetta Pace ◽  
Serena Di Vincenzo ◽  
Donatella Valenti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoke ◽  
Room Temperature ◽  
Cigarette Smoke Extract ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Bronchial Epithelial ◽  
Promising Tool ◽  
Next Generation Impactor

In this work beclomethasone dipropionate was loaded into liposomes and hyalurosomes modified with mucin to improve the ability of the payload to counteract the oxidative stress and involved damages caused by cigarette smoke in the airway. The vesicles were prepared by dispersing all components in the appropriate vehicle and sonicating them, thus avoiding the use of organic solvents. Unilamellar and bilamellar vesicles small in size (~117 nm), homogeneously dispersed (polydispersity index lower than 0.22) and negatively charged (~−11 mV), were obtained. Moreover, these vesicle dispersions were stable for five months at room temperature (~25 °C). In vitro studies performed using the Next Generation Impactor confirmed the suitability of the formulations to be nebulized as they were capable of reaching the last stages of the impactor that mimic the deeper airways, thus improving the deposition of beclomethasone in the target site. Further, biocompatibility studies performed by using 16HBE bronchial epithelial cells confirmed the high biocompatibility and safety of all the vesicles. Among the tested formulations, only mucin-hyalurosomes were capable of effectively counteracting the production of reactive oxygen species (ROS) induced by cigarette smoke extract, suggesting that this formulation may represent a promising tool to reduce the damaging effects of cigarette smoke in the lung tissues, thus reducing the pathogenesis of cigarette smoke-associated diseases such as chronic obstructive pulmonary disease, emphysema, and cancer.

scholarly journals Rosuvastatin Attenuated Elastic Fiber Degradation in Chronic Obstructive Pulmonary Disease Sprague-Dawley Rats

2019 ◽  
Vol 30 (3) ◽  
pp. 175
Author(s):  
Rahmaningsih Mara Sabirin ◽  
Prasetyastuti ◽  
Denny Agustiningsih
Keyword(s):  
Oxidative Stress ◽  
Chronic Obstructive Pulmonary Disease ◽  
Cigarette Smoke ◽  
Elastic Fiber ◽  
Degradation Process ◽  
Chronic Obstructive ◽  
Sprague Dawley ◽  
Obstructive Pulmonary Disease ◽  
Fiber Degradation ◽  
Sprague Dawley Rats

<p>Chronic obstructive pulmonary disease (COPD) is an incurable disease which causes disability and death. The main pathogenesis of COPD is oxidative stress due to cigarette smoke which initiates various reactions and lead to lung elastic fibers destruction. Statins are known to have antioxidant effects and reduce mortality in COPD. We studied the effects of cigarette smoke exposure cessation and rosuvastatin on oxidative stress and the level of elastic fiber destruction in COPD model rats. Thirty 10-week old male Sprague-Dawley rats were divided into 2 groups: Control (n=6, did not received fumigation nor treatment) and Smoking (n=24, received fumigation for 70 days) groups. Afterwards, the smoking group was divided into 4 groups: Sham, R2, R5,R10, and received 0.9% NaCl, 2.5, 5 and 10 mg/kg/day of rosuvastatin, respectively. Examination of malondialdehyde (MDA) and desmosine serum were conducted to measure oxidative stress and elastic fiber degradation level, respectively. After smoke exposure, MDA and desmosine levels of COPD rats were found to be significantly higher (p=0.000 and 0.000) than controls. The MDA level in Sham, R2, R5 and R10 groups decreased significantly after therapy (p=0.000; 0.033; 0.015; 0.002). However, the post-treatment desmosine level was increase significantly in Sham and R2 groups (p=0.006 dan 0.012) and insignificantly (p=0.117 dan 0.278) in the R5 and R10 groups. It can be concluded that the cessation of exposure to cigarette smoke can reduce oxidative stress, but not elastic degradation process. The administration of rosuvastatin of 5 or 10 mg/kg/day attenuated elastic degradation process.</p>

scholarly journals Astaxanthin Suppresses Cigarette Smoke-Induced Emphysema through Nrf2 Activation in Mice

Marine Drugs ◽  
2019 ◽  
Vol 17 (12) ◽  
pp. 673 ◽  
Author(s):  
Hiroaki Kubo ◽  
Kazuhisa Asai ◽  
Kazuya Kojima ◽  
Arata Sugitani ◽  
Yohkoh Kyomoto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoke ◽  
Defense Mechanism ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Obstructive Pulmonary Disease ◽  
Suppression Effect

Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is a key cellular defense mechanism against oxidative stress. Recent studies have shown that astaxanthin protects against oxidative stress via Nrf2. In this study, we investigated the emphysema suppression effect of astaxanthin via Nrf2 in mice. Mice were divided into four groups: control, smoking, astaxanthin, and astaxanthin + smoking. The mice in the smoking and astaxanthin + smoking groups were exposed to cigarette smoke for 12 weeks, and the mice in the astaxanthin and astaxanthin + smoking groups were fed a diet containing astaxanthin. Significantly increased expression levels of Nrf2 and its target gene, heme oxygenase-1 (HO-1), were found in the lung homogenates of astaxanthin-fed mice. The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) was significantly decreased, and emphysema was significantly suppressed. In conclusion, astaxanthin protects against oxidative stress via Nrf2 and ameliorates cigarette smoke-induced emphysema. Therapy with astaxanthin directed toward activating the Nrf2 pathway has the potential to be a novel preventive and therapeutic strategy for COPD.

scholarly journals An Update on the Role of Nrf2 in Respiratory Disease: Molecular Mechanisms and Therapeutic Approaches

2021 ◽  
Vol 22 (16) ◽  
pp. 8406
Author(s):  
Jooyeon Lee ◽  
Jimin Jang ◽  
Sung-Min Park ◽  
Se-Ran Yang
Keyword(s):  
Oxidative Stress ◽  
Respiratory Diseases ◽  
Molecular Mechanisms ◽  
Antioxidant Response ◽  
Atmospheric Environment ◽  
Chronic Obstructive ◽  
Related Factor ◽  
Protective Effects ◽  
Cell Protection ◽  
Obstructive Pulmonary Disease

Nuclear factor erythroid 2-related factor (Nrf2) is a transcriptional activator of the cell protection gene that binds to the antioxidant response element (ARE). Therefore, Nrf2 protects cells and tissues from oxidative stress. Normally, Kelch-like ECH-associated protein 1 (Keap1) inhibits the activation of Nrf2 by binding to Nrf2 and contributes to Nrf2 break down by ubiquitin proteasomes. In moderate oxidative stress, Keap1 is inhibited, allowing Nrf2 to be translocated to the nucleus, which acts as an antioxidant. However, under unusually severe oxidative stress, the Keap1-Nrf2 mechanism becomes disrupted and results in cell and tissue damage. Oxide-containing atmospheric environment generally contributes to the development of respiratory diseases, possibly leading to the failure of the Keap1-Nrf2 pathway. Until now, several studies have identified changes in Keap1-Nrf2 signaling in models of respiratory diseases, such as acute respiratory distress syndrome (ARDS)/acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and asthma. These studies have confirmed that several Nrf2 activators can alleviate symptoms of respiratory diseases. Thus, this review describes how the expression of Keap1-Nrf2 functions in different respiratory diseases and explains the protective effects of reversing this expression.

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