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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.

SUBMITTER: Chambellan A

PROVIDER: S-EPMC2643263 | biostudies-literature | 2006 Oct

REPOSITORIES: biostudies-literature

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Gene expression profile of human airway epithelium induced by hyperoxia in vivo.

Chambellan Arnaud A Cruickshank Paul J PJ McKenzie Patrick P Cannady Steven B SB Szabo Katalin K Comhair Suzy A A SA Erzurum Serpil C SC

American journal of respiratory cell and molecular biology 20060511 4

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 ...[more]

PMID: 16690988

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Project description:Cigarette smoking is a leading cause of preventable death and a significant cause of lung cancer and chronic obstructive pulmonary disease. Prior studies have demonstrated that smoking creates a field of molecular injury throughout the airway epithelium exposed to cigarette smoke. We have previously characterized gene expression in the bronchial epithelium of never smokers and identified the gene expression changes that occur in the mainstem bronchus in response to smoking. In this study, we explored relationships in whole-genome gene expression between extrathorcic (buccal and nasal) and intrathoracic (bronchial) epithelium in healthy current and never smokers.Using genes that have been previously defined as being expressed in the bronchial airway of never smokers (the "normal airway transcriptome"), we found that bronchial and nasal epithelium from non-smokers were most similar in gene expression when compared to other epithelial and nonepithelial tissues, with several antioxidant, detoxification, and structural genes being highly expressed in both the bronchus and nose. Principle component analysis of previously defined smoking-induced genes from the bronchus suggested that smoking had a similar effect on gene expression in nasal epithelium. Gene set enrichment analysis demonstrated that this set of genes was also highly enriched among the genes most altered by smoking in both nasal and buccal epithelial samples. The expression of several detoxification genes was commonly altered by smoking in all three respiratory epithelial tissues, suggesting a common airway-wide response to tobacco exposure.Our findings support a relationship between gene expression in extra- and intrathoracic airway epithelial cells and extend the concept of a smoking-induced field of injury to epithelial cells that line the mouth and nose. This relationship could potentially be utilized to develop a non-invasive biomarker for tobacco exposure as well as a non-invasive screening or diagnostic tool providing information about individual susceptibility to smoking-induced lung diseases.

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Gene expression profile of human airway epithelium induced by hyperoxia in vivo.

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Gene expression profile of human airway epithelium induced by hyperoxia in vivo.

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