scholarly journals Sirtuin 3 Inhibits Airway Epithelial Mitochondrial Oxidative Stress in Cigarette Smoke-Induced COPD

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Ming Zhang ◽  
Yeli Zhang ◽  
Michael Roth ◽  
Li Zhang ◽  
Rong Shi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Cigarette Smoke ◽  
Airway Epithelium ◽  
Cell Injury ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Sirtuin 3 ◽  
Mitochondrial Oxidative Stress ◽  
Expression And Activity

Mitochondrial damage in airway epithelial cells plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Sirtuin 3 (Sirt3) is a mitochondrial deacetylase regulating mitochondrial function, but its role in the pathogenesis of COPD is still unknown. The aim of the present study was to investigate the effect of Sirt3 on airway epithelial mitochondria in cigarette smoke-induced COPD. Our present study has shown serious airway inflammation, alveolar space enlargement, and mitochondrial damage of the airway epithelium in COPD rats. Compared to the control rats, Sirt3 protein expression was significantly decreased in the airway epithelium and lung tissue homogenate from COPD rats. In airway epithelial cells (BEAS-2B), cigarette smoke extract (CSE) treatment significantly decreased mRNA and protein expression of Sirt3 and manganese superoxide dismutase (MnSOD), as well as MnSOD activity in a concentration and time-dependent manner. Sirt3 siRNA further significantly intensified the decreases in MnSOD expression and activity and aggravated mitochondrial oxidative stress and cell injury when airway epithelial cells were treated with 7.5% CSE. In contrast, Sirt3 overexpression significantly prevented the decrease of MnSOD expression and activity and improved mitochondrial oxidative stress and cell injury in CSE-treated airway epithelial cells. These data suggest that Sirt3 inhibits airway epithelial mitochondrial oxidative stress possibly through the regulation of MnSOD, thereby contributing to the pathogenesis of COPD.

scholarly journals A Protective Role of FAM13A in Human Airway Epithelial Cells Upon Exposure to Cigarette Smoke Extract

2021 ◽  
Vol 12 ◽  
Author(s):  
Qing Chen ◽  
Maaike de Vries ◽  
Kingsley Okechukwu Nwozor ◽  
Jacobien A. Noordhoek ◽  
Corry-Anke Brandsma ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cigarette Smoking ◽  
Cigarette Smoke ◽  
Airway Epithelium ◽  
Barrier Function ◽  
Cigarette Smoke Extract ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Copd Patients ◽  
Epithelial Resistance

BackgroundChronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease characterized by chronic inflammation upon inhalation of noxious particles, e.g., cigarette smoke. FAM13A is one of the genes often found to be associated with COPD, however its function in the pathophysiology of COPD is incompletely understood. We studied its role in airway epithelial barrier integrity and cigarette smoke-induced epithelial responses.Materials and MethodsProtein level and localization of FAM13A was assessed with immunohistochemistry in lung tissue from COPD patients and non-COPD controls. In vitro, FAM13A expression was determined in the absence or presence of cigarette smoke extract (CSE) in primary airway epithelial cells (AECs) from COPD patients and controls by western blotting. FAM13A was overexpressed in cell line 16HBE14o- and its effect on barrier function was monitored real-time by electrical resistance. Expression of junctional protein E-cadherin and β-catenin was assessed by western blotting. The secretion of neutrophil attractant CXCL8 upon CSE exposure was measured by ELISA.ResultsFAM13A was strongly expressed in airway epithelium, but significantly weaker in airways of COPD patients compared to non-COPD controls. In COPD-derived AECs, but not those of controls, FAM13A was significantly downregulated by CSE. 16HBE14o- cells overexpressing FAM13A built up epithelial resistance significantly more rapidly, which was accompanied by higher E-cadherin expression and reduced CSE-induced CXCL8 levels.ConclusionOur data indicate that the expression of FAM13A is lower in airway epithelium of COPD patients compared to non-COPD controls. In addition, cigarette smoking selectively downregulates airway epithelial expression of FAM13A in COPD patients. This may have important consequences for the pathophysiology of COPD, as the more rapid build-up of epithelial resistance upon FAM13A overexpression suggests improved (re)constitution of barrier function. The reduced epithelial secretion of CXCL8 upon CSE-induced damage suggests that lower FAM13A expression upon cigarette smoking may facilitate epithelial-driven neutrophilia.

scholarly journals p66Shc Mediates Mitochondrial Dysfunction Dependent on PKC Activation in Airway Epithelial Cells Induced by Cigarette Smoke

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Ming Zhang ◽  
Jingjing Tang ◽  
Hu Shan ◽  
Qiuhong Zhang ◽  
Xia Yang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mitochondrial Dysfunction ◽  
Cigarette Smoke ◽  
Cell Injury ◽  
Critical Role ◽  
Adaptor Protein ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Mitochondrial Injury ◽  
Mitochondrial Translocation

Airway epithelial mitochondrial injury plays a critical role in the pathogenesis of chronic obstructive pulmonary disease (COPD). The p66Shc adaptor protein is a newly recognized mediator of mitochondrial dysfunction. However, little is known about the effect of p66Shc on airway epithelial damage in the development of COPD. The aim of the present study is to investigate the roles of p66Shc and its upstream regulators in the mitochondrial injury of airway epithelial cells (Beas-2b) induced by cigarette smoke extract (CSE). Our present study revealed that CSE increased p66Shc expression and its mitochondrial translocation in concentration and time-dependent manners in airway epithelial cells. And p66Shc siRNA significantly attenuated mitochondrial dysfunction and cell injury when airway epithelial cells were stimulated with 7.5% CSE. The total and phosphorylated expression of PKCβ and PKCδ was significantly increased associated with mitochondrial dysfunction and cell injury when airway epithelial cells were exposed to 7.5% CSE. The pretreatments with pharmacological inhibitors of PKCβ and PKCδ could notably suppress p66Shc phosphorylation and its mitochondrial translocation and protect the mitochondria and cells against oxidative damage when airway epithelial cells were incubated with 7.5% CSE. These data suggest that a novel PKCβ/δ-p66Shc signaling pathway may be involved in the pathogenesis of COPD and other oxidative stress-associated pulmonary diseases and provide a potential therapeutic target for these diseases.

scholarly journals Ozone effect on inflammatory and proteomic profile of human macrophages and airway epithelial cells

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
L Falcone ◽  
E Aruffo ◽  
P Di Carlo ◽  
P Del Boccio ◽  
M C Cufaro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Air Pollution ◽  
Epithelial Cells ◽  
Cell Lines ◽  
Urban Areas ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Proteomics Analysis ◽  
Human Macrophages ◽  
Tnf Α

Abstract Background Reactive oxygen species (ROS) and oxidative stress in the respiratory system are involved in lung inflammation and tumorigenesis. Ozone (O3) is one of the main components of air pollution in urban areas able to act as strong pro-oxidant agent, however its effects on human health is still poorly investigated. In this study the effect of O3 has been evaluated in THP-1 monocytes differentiated into macrophages with PMA and in HBEpC (primary human bronchial epithelial) cells, two model systems for in vitro studies and translational research. Methods Cell viability, ROS and pro-inflammatory cytokines like interleukin-8(IL-8) and tumor necrosis factor(TNF-α) have been tested in the above-mentioned cell lines not exposed to any kind of pollution (basal condition-b.c.) or exposed to O3 at a concentration of 120 ppb. In HBEpC a labelfree shotgun proteomics analysis has been also performed in the same conditions. Results Ozone significantly increased the production of IL-8 and TNF-α in THP-1 whereas no changes were shown in HBEpC. In both cell lines lipopolysaccharide(LPS) caused an increase of IL-8 and TNF-α production in b.c. and O3 treatment potentiated this effect. Ozone exposure increased ROS formation in a time dependent manner in both cell lines and in THP-1 cells a decrease in catalase activity was also shown. Finally, according to these data, functional proteomics analysis revealed that in HBEpC exposure to O3 many differential proteins are related to oxidative stress and inflammation. Conclusions Our results indicate that O3, at levels that can be reached in urban areas, causes an increase of pro-inflammatory agents either per se or potentiating the effect of immune response stimulators in cell models of human macrophages and human airway epithelial cells. Interestingly, the proteomic analysis showed that besides the dysregulated proteins, O3 induced the expression of AKR1D1 and AKR1B10, proteins recognized to play a significant role in cancer development. Key messages This study adds new pieces of information on the association between O3 exposure and detrimental effects on respiratory system. This study suggests the need for further research on the mechanisms involved and for a continued monitoring/re-evaluation of air pollution standards aimed at safeguarding human health.

scholarly journals Somatic cell hemoglobin modulates nitrogen oxide metabolism in the human airway epithelium

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nadzeya Marozkina ◽  
Laura Smith ◽  
Yi Zhao ◽  
Joe Zein ◽  
James F. Chmiel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Nitrogen Oxides ◽  
Airway Epithelium ◽  
Airflow Obstruction ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Human Airway Epithelial Cells

AbstractEndothelial hemoglobin (Hb)α regulates endothelial nitric oxide synthase (eNOS) biochemistry. We hypothesized that Hb could also be expressed and biochemically active in the ciliated human airway epithelium. Primary human airway epithelial cells, cultured at air–liquid interface (ALI), were obtained by clinical airway brushings or from explanted lungs. Human airway Hb mRNA data were from publically available databases; or from RT-PCR. Hb proteins were identified by immunoprecipitation, immunoblot, immunohistochemistry, immunofluorescence and liquid chromatography- mass spectrometry. Viral vectors were used to alter Hbβ expression. Heme and nitrogen oxides were measured colorimetrically. Hb mRNA was expressed in human ciliated epithelial cells. Heme proteins (Hbα, β, and δ) were detected in ALI cultures by several methods. Higher levels of airway epithelial Hbβ gene expression were associated with lower FEV1 in asthma. Both Hbβ knockdown and overexpression affected cell morphology. Hbβ and eNOS were apically colocalized. Binding heme with CO decreased extracellular accumulation of nitrogen oxides. Human airway epithelial cells express Hb. Higher levels of Hbβ gene expression were associated with airflow obstruction. Hbβ and eNOS were colocalized in ciliated cells, and heme affected oxidation of the NOS product. Epithelial Hb expression may be relevant to human airways diseases.

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