title: Alterations of bronchial epithelial metabolome by cigarette smoke are reversible by an antioxidant, O-methyl-L-tyrosinyl-γ-L-glutamyl-L-cysteinylglycine.
abstract: Human bronchial epithelial cells (HBECs) have first-line contact with harmful substances during smoking, and changes in their metabolism most likely represent a defining factor in coping with the stress and development of airway diseases. This study was designed to determine the dynamics of metabolome changes in HBECs treated with cigarette smoke condensate (CSC), and to test whether normal metabolism can be restored by synthetic antioxidants. Principal component analysis, based on untargeted mass spectra, indicated that treatment of CSC-exposed HBECs with O-methyl-L-tyrosinyl-γ-L-glutamyl-L-cysteinylglycine (UPF1) acted faster than did N-acetylcysteine to revert the effect of CSC. The maximum effect of 10 μg/ml CSC itself on HBEC cell line, BEAS-2B, metabolism was seen at 2 hours after treatment, with return to the baseline level by 7 hours. In primary HBECs, the initial maximum effect was seen at 1 hour after CSC exposure. Certain metabolites associated with redox pathways and energy production were affected by CSC. Subsequent restoration of their content by UPF1 supports the hypothetical protective capacity of UPF1 against the oxidative stress and increased energy demand, respectively. Furthermore, UPF1 up-regulated the contents of phospholipid species identified as phosphatidylcholines and phosphatidylethanolamines in the CSC-exposed HBECs, indicating possible suppression of inflammatory processes along with an increase in spermidine as an endogenous cytoprotector. In conclusion, with this dynamic metabolomics study, we characterize the durability of the CSC-induced metabolic changes in BEAS-2B line cells and primary HBECs, and demonstrate the ability of UPF1 to significantly accelerate the recovery of HBECs from CSC insult.
authors.affiliation: 1 Department of Biochemistry, Institute of Biomedicine and Translational Medicine, University of Tartu, the Centre of Excellence for Translational Medicine, Tartu, Estonia.
authors.forename: Argo
authors.initials: A
authors.lastname: Aug
authors.forename: Alan
authors.initials: A
authors.lastname: Altraja
authors.forename: Siiri
authors.initials: S
authors.lastname: Altraja
authors.forename: Liisi
authors.initials: L
authors.lastname: Laaniste
authors.forename: Riina
authors.initials: R
authors.lastname: Mahlapuu
authors.forename: Ursel
authors.initials: U
authors.lastname: Soomets
authors.forename: Kalle
authors.initials: K
authors.lastname: Kilk
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D016000:Cluster Analysis; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods; D018384:Oxidative Stress / Q000187:drug effects*; D010743:Phospholipids / Q000378:metabolism; D025341:Principal Component Analysis; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013095:Spermidine / Q000378:metabolism; D013997:Time Factors
chemical_list: C529051:4-methoxy-1-tyrosyl-gamma-glutamyl-cysteinyl-glycine; D000975:Antioxidants; D010743:Phospholipids; D012906:Smoke; D005978:Glutathione; D013095:Spermidine
keywords: O-methyl-l-tyrosinyl-γ-l-glutamyl-l-cysteinylglycine; antioxidants; cigarette smoke; human bronchial epithelial cells; metabolome