title: Gene expression profile of human airway epithelium induced by hyperoxia in vivo.
abstract: Hyperoxia leads to oxidative modification and damage of macromolecules in the respiratory tract with loss of biological functions. Given the lack of antioxidant gene induction with acute exposure to 100% oxygen, we hypothesized that clearance pathways for oxidatively modified proteins may be induced and serve in the immediate cellular response to preserve the epithelial layer. To test this, airway epithelial cells were obtained from individuals under ambient oxygen conditions and after breathing 100% oxygen for 12 h. Gene expression profiling identified induction of genes in the chaperone and proteasome-ubiquitin-conjugation pathways that together comprise an integrated cellular response to manage and degrade damaged proteins. Analyses also revealed gene expression changes associated with oxidoreductase function, cell cycle regulation, and ATP synthesis. Increased HSP70, protein ubiquitination, and intracellular ATP were validated in cells exposed to hyperoxia in vitro. Inhibition of proteasomal degradation revealed the importance of accelerated protein catabolism for energy production of cells exposed to hyperoxia. Thus, the human airway early response to hyperoxia relies predominantly upon induction of cytoprotective chaperones and the ubiquitin-proteasome-dependent protein degradation system to maintain airway homeostatic integrity.
authors.affiliation: Institut du Thorax, INSERM U533, Faculté de Médecine, Nantes, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Chambellan
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Cruickshank
authors.forename: Patrick
authors.initials: P
authors.lastname: McKenzie
authors.forename: Steven B
authors.initials: SB
authors.lastname: Cannady
authors.forename: Katalin
authors.initials: K
authors.lastname: Szabo
authors.forename: Suzy A A
authors.initials: SA
authors.lastname: Comhair
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D001980:Bronchi / Q000378:metabolism; D002461:Cell Line, Transformed; D016000:Cluster Analysis; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D018496:Hyperoxia / Q000235:genetics*; D008297:Male; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000032:analysis; D020545:Respiratory Mucosa / Q000378:metabolism*; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D025801:Ubiquitin; D000255:Adenosine Triphosphate