Glutathione Peroxidase-1 Suppresses the Unfolded Protein Response upon Cigarette Smoke Exposure

Patrick Geraghty, Nathalie Baumlin, Matthias A Salathe, Robert F. Foronjy, Jeanine M. D'Armiento

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Oxidative stress provokes endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) in the lungs of chronic obstructive pulmonary (COPD) subjects. The antioxidant, glutathione peroxidase-1 (GPx-1), counters oxidative stress induced by cigarette smoke exposure. Here, we investigate whether GPx-1 expression deters the UPR following exposure to cigarette smoke. Expression of ER stress markers was investigated in fully differentiated normal human bronchial epithelial (NHBE) cells isolated from nonsmoking, smoking, and COPD donors and redifferentiated at the air liquid interface. NHBE cells from COPD donors expressed heightened ATF4, XBP1, GRP78, GRP94, EDEM1, and CHOP compared to cells from nonsmoking donors. These changes coincided with reduced GPx-1 expression. Reintroduction of GPx-1 into NHBE cells isolated from COPD donors reduced the UPR. To determine whether the loss of GPx-1 expression has a direct impact on these ER stress markers during smoke exposure, Gpx-1-/- mice were exposed to cigarette smoke for 1 year. Loss of Gpx-1 expression enhanced cigarette smoke-induced ER stress and apoptosis. Equally, induction of ER stress with tunicamycin enhanced antioxidant expression in mouse precision-cut lung slices. Smoke inhalation also exacerbated the UPR response during respiratory syncytial virus infection. Therefore, ER stress may be an antioxidant-related pathophysiological event in COPD.

Original languageEnglish (US)
Article number9461289
JournalMediators of Inflammation
Volume2016
DOIs
StatePublished - 2016

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Unfolded Protein Response
Endoplasmic Reticulum Stress
Smoke
Tobacco Products
Chronic Obstructive Pulmonary Disease
Antioxidants
Epithelial Cells
Lung
Oxidative Stress
Respiratory Syncytial Virus Infections
Tunicamycin
Inhalation
Glutathione
glutathione peroxidase GPX1
Smoking
Air
Apoptosis

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Geraghty, P., Baumlin, N., Salathe, M. A., Foronjy, R. F., & D'Armiento, J. M. (2016). Glutathione Peroxidase-1 Suppresses the Unfolded Protein Response upon Cigarette Smoke Exposure. Mediators of Inflammation, 2016, [9461289]. https://doi.org/10.1155/2016/9461289

Glutathione Peroxidase-1 Suppresses the Unfolded Protein Response upon Cigarette Smoke Exposure. / Geraghty, Patrick; Baumlin, Nathalie; Salathe, Matthias A; Foronjy, Robert F.; D'Armiento, Jeanine M.

In: Mediators of Inflammation, Vol. 2016, 9461289, 2016.

Research output: Contribution to journalArticle

Geraghty, Patrick ; Baumlin, Nathalie ; Salathe, Matthias A ; Foronjy, Robert F. ; D'Armiento, Jeanine M. / Glutathione Peroxidase-1 Suppresses the Unfolded Protein Response upon Cigarette Smoke Exposure. In: Mediators of Inflammation. 2016 ; Vol. 2016.
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