title: Short- and long- term effects of cigarette smoke exposure on glutathione homeostasis in human bronchial epithelial cells.
abstract: BACKGROUND
  Cigarette smoke extract (CSE), a model for studying the effects of tobacco smoke in vivo and in vitro, induces cell oxidative stress and affects the antioxidative glutathione system. We evaluated the impact of CSE on airway epithelial cells and the possible cytoprotective effect of the mucolitic drug S-carboximethilcysteine lysine salt (S-CMC-Lys).
  
  
  METHODS
  Reduced glutathione (GSH) and reactive oxygen species (ROS) intracellular levels were evaluated by fluorimetry in human bronchial epithelial cells (16-HBE) and the expression and activity of enzymes of the GSH metabolic pathway were investigated by RT-PCR, Western blot and colorimetric assays.
  
  
  RESULTS
  CSE significantly increased cell mortality in a time and dose dependent manner, via an apoptosis-independent pathway. Short-term (3 hours) CSE exposure induced an increase in ROS levels and a GSH intracellular concentration drop. In parallel, the expression of glutathione peroxidases 2 and 3, glutathione reductase and glutamate-cysteine-ligase was increased. S-CMC-Lys was effective in counteracting these effects.
  
  
  CONCLUSIONS
  CSE affects ROS levels, GSH concentration and GSH enzymes pathway. These effects can be to some extent reversed by S-CMC-Lys, that could represent a therapeutic tool to counteract CSE induced oxidative cellular injuries.
authors.affiliation: Department of Biosciences, University of Milan, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bazzini
authors.forename: Valeria
authors.initials: V
authors.lastname: Rossetti
authors.forename: Davide Antonio
authors.initials: DA
authors.lastname: Civello
authors.forename: Francesca
authors.initials: F
authors.lastname: Sassone
authors.forename: Valeria
authors.initials: V
authors.lastname: Vezzoli
authors.forename: Luca
authors.initials: L
authors.lastname: Persani
authors.forename: Laura
authors.initials: L
authors.lastname: Tiberio
authors.forename: Luigi
authors.initials: L
authors.lastname: Lanata
authors.forename: Michela
authors.initials: M
authors.lastname: Bagnasco
authors.forename: Markus
authors.initials: M
authors.lastname: Paulmichl
authors.forename: Giuliano
authors.initials: G
authors.lastname: Meyer
authors.forename: Maria Lisa
authors.initials: ML
authors.lastname: Garavaglia
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D005978:Glutathione