title: Ethanol alters alveolar fluid balance via Nadph oxidase (NOX) signaling to epithelial sodium channels (ENaC) in the lung.
abstract: Chronic alcohol consumption is associated with increased incidence of ICU-related morbidity and mortality, primarily from acute respiratory distress syndrome (ARDS). However, the mechanisms involved are unknown. One explanation is that alcohol regulates epithelial sodium channels (ENaC) via oxidant signaling to promote a pro- injury environment. We used small rodent models to mimic acute and chronic alcohol consumption and tested the hypothesis that ethanol (EtOH) would affect lung fluid clearance by up-regulating ENaC activity in the lung. Fluorescence labeling of rat lung slices and in vivo mouse lung revealed an increase in ROS production in response to acute EtOH exposure. Using western blots and fluorescein-5-maleimide labeling, we conclude that EtOH exposure modifies cysteines of α-ENaC while data from single channel patch clamp analysis confirm that 0.16% EtOH increased ENaC activity in rat alveolar cells. In vivo lung fluid clearance demonstrated a latent increase in fluid clearance in mice receiving EtOH diet. Ethanol mice given a tracheal instillation of LPS demonstrated early lung fluid clearance compared to caloric control mice and C57Bl/6 mice. Standard biochemical techniques reveal that chronic EtOH consumption resulted in greater protein expression of the catalytic gp91(phox) subunit and the obligate Rac1 protein. Collectively these data suggest that chronic EtOH consumption may lead to altered regulation of ENaC, contributing to a 'pro-injury' environment in the alcohol lung.
authors: Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia, USA. mhelms@emory.edu
authors: Charles A
authors: CA
authors: Downs
authors: David Q
authors: DQ
authors: Trac
authors: Lisa H
authors: LH
authors: Kreiner
authors: Amity F
authors: AF
authors: Eaton
authors: Nicholle M
authors: NM
authors: Johnson
authors: Lou Ann
authors: LA
authors: Brown
authors: My N
authors: MN
authors: Helms
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D053503:Epithelial Sodium Channels / Q000737:chemistry / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D019255:NADPH Oxidases / Q000378:metabolism*; D010084:Oxidation-Reduction; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014882:Water-Electrolyte Balance; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D053503:Epithelial Sodium Channels; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D000431:Ethanol; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; D020830:rac1 GTP-Binding Protein
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