Cigarette smoke irreversibly modifies glutathione in airway epithelial cells

2007 ◽  
Vol 293 (5) ◽  
pp. L1156-L1162 ◽  
Author(s):  
Marco van der Toorn ◽  
Maria P. Smit-de Vries ◽  
Dirk-Jan Slebos ◽  
Harold G. de Bruin ◽  
Nicolas Abello ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cigarette Smoke ◽  
A549 Cells ◽  
Airway Epithelial Cells ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Obstructive Pulmonary Disease ◽  
Bronchial Epithelial ◽  
Gsh Metabolism ◽  
Primary Bronchial Epithelial Cells

In patients with chronic obstructive pulmonary disease (COPD), an imbalance between oxidants and antioxidants is acknowledged to result in disease development and progression. Cigarette smoke (CS) is known to deplete total glutathione (GSH + GSSG) in the airways. We hypothesized that components in the gaseous phase of CS may irreversibly react with GSH to form GSH derivatives that cannot be reduced (GSX), thereby causing this depletion. To understand this phenomenon, we investigated the effect of CS on GSH metabolism and identified the actual GSX compounds. CS and H2O2 (control) deplete reduced GSH in solution [Δ = −54.1 ± 1.7 μM ( P < 0.01) and −39.8 ± 0.9 μM ( P < 0.01), respectively]. However, a significant decrease of GSH + GSSG was observed after CS (Δ = −75.1 ± 7.6 μM, P < 0.01), but not after H2O2. Exposure of A549 cells and primary bronchial epithelial cells to CS decreased free sulfhydryl (-SH) groups (Δ = −64.2 ± 14.6 μM/mg protein, P < 0.05) and irreversibly modified GSH + GSSG (Δ = −17.7 ± 1.9 μM, P < 0.01) compared with nonexposed cells or H2O2 control. Mass spectrometry (MS) showed that GSH was modified to glutathione-aldehyde derivatives. Further MS identification showed that GSH was bound to acrolein and crotonaldehyde and another, yet to be identified, structure. Our data show that CS does not oxidize GSH to GSSG but, rather, reacts to nonreducible glutathione-aldehyde derivatives, thereby depleting the total available GSH pool.

scholarly journals Antibacterial Defense of Human Airway Epithelial Cells from Chronic Obstructive Pulmonary Disease Patients Induced by Acute Exposure to Nontypeable Haemophilus influenzae: Modulation by Cigarette Smoke

2017 ◽  
Vol 9 (4) ◽  
pp. 359-374 ◽  
Author(s):  
Gimano D. Amatngalim ◽  
Jasmijn A. Schrumpf ◽  
Almira Henic ◽  
Esther Dronkers ◽  
Renate M. Verhoosel ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Antibacterial Activity ◽  
Epithelial Cells ◽  
Haemophilus Influenzae ◽  
Cigarette Smoke ◽  
Airway Epithelial Cells ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Nontypeable Haemophilus Influenzae ◽  
Obstructive Pulmonary Disease

Antimicrobial proteins and peptides (AMPs) are a central component of the antibacterial activity of airway epithelial cells. It has been proposed that a decrease in antibacterial lung defense contributes to an increased susceptibility to microbial infection in smokers and patients with chronic obstructive pulmonary disease (COPD). However, whether reduced AMP expression in the epithelium contributes to this lower defense is largely unknown. We investigated the bacterial killing activity and expression of AMPs by air-liquid interface-cultured primary bronchial epithelial cells from COPD patients and non-COPD (ex-)smokers that were stimulated with nontypeable Haemophilus influenzae (NTHi). In addition, the effect of cigarette smoke on AMP expression and the activation of signaling pathways was determined. COPD cell cultures displayed reduced antibacterial activity, whereas smoke exposure suppressed the NTHi-induced expression of AMPs and further increased IL-8 expression in COPD and non-COPD cultures. Moreover, smoke exposure impaired NTHi-induced activation of NF-κB, but not MAP-kinase signaling. Our findings demonstrate that the antibacterial activity of cultured airway epithelial cells induced by acute bacterial exposure was reduced in COPD and suppressed by cigarette smoke, whereas inflammatory responses persisted. These findings help to explain the imbalance between protective antibacterial and destructive inflammatory innate immune responses in COPD.

scholarly journals Adenine nucleotide translocase regulates airway epithelial metabolism, surface hydration and ciliary function

2021 ◽  
Vol 134 (4) ◽  
pp. jcs257162 ◽  
Author(s):  
Corrine R. Kliment ◽  
Jennifer M. K. Nguyen ◽  
Mary Jane Kaltreider ◽  
YaWen Lu ◽  
Steven M. Claypool ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cigarette Smoke ◽  
Adenine Nucleotide ◽  
Airway Epithelial Cells ◽  
Adenine Nucleotide Translocase ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Ciliary Function ◽  
Transporter Family ◽  
Surface Hydration

ABSTRACTAirway hydration and ciliary function are critical to airway homeostasis and dysregulated in chronic obstructive pulmonary disease (COPD), which is impacted by cigarette smoking and has no therapeutic options. We utilized a high-copy cDNA library genetic selection approach in the amoeba Dictyostelium discoideum to identify genetic protectors to cigarette smoke. Members of the mitochondrial ADP/ATP transporter family adenine nucleotide translocase (ANT) are protective against cigarette smoke in Dictyostelium and human bronchial epithelial cells. Gene expression of ANT2 is reduced in lung tissue from COPD patients and in a mouse smoking model, and overexpression of ANT1 and ANT2 resulted in enhanced oxidative respiration and ATP flux. In addition to the presence of ANT proteins in the mitochondria, they reside at the plasma membrane in airway epithelial cells and regulate airway homeostasis. ANT2 overexpression stimulates airway surface hydration by ATP and maintains ciliary beating after exposure to cigarette smoke, both of which are key functions of the airway. Our study highlights a potential for upregulation of ANT proteins and/or of their agonists in the protection from dysfunctional mitochondrial metabolism, airway hydration and ciliary motility in COPD.This article has an associated First Person interview with the first author of the paper.

scholarly journals ACE2 Expression is elevated in Airway Epithelial Cells from aged and male donors but reduced in asthma

2020 ◽  
Author(s):  
Peter Wark ◽  
Prabuddha Pathinyake ◽  
Gerard Kaiko ◽  
Kristy Nichol ◽  
Ayesha Ali ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Serine Proteases ◽  
Airway Epithelial Cells ◽  
Lower Airway ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Obstructive Pulmonary Disease ◽  
Protein Levels ◽  
Asthma Patients

Rationale: COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter airway epithelial cells (AECs). Objective: To determine what factors are associated with ACE2 expression particularly in patients with asthma and chronic obstructive pulmonary disease (COPD). Methods: We obtained upper and lower AECs from 145 people from two independent cohorts, aged 2-89, Newcastle (n=115), and from Perth (n= 30) Australia. The Newcastle cohort was enriched with people with asthma (n=37) and COPD (n=38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry were assessed by quantitative PCR, protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AECs. Results: Increased gene expression of ACE2 was associated with older age (p=0.02) and male sex (p=0.03), but not pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma (p=0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in asthma (p=0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface was increased (p=0.02). ACE2 protein levels were lower in endobronchial biopsies from asthma patients. Conclusions: Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications.

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