title: Chronic ethanol exposure alters the lung proteome and leads to mitochondrial dysfunction in alveolar type 2 cells.
abstract: The lungs can undergo irreversible damage from chronic alcohol consumption. Herein, we developed an animal model predisposed for edematous lung injury following chronic ingestion of alcohol to better understand the etiology of alcohol-related disorders. Using animal modeling, alongside high-throughput proteomic and microarray assays, we identified changes in lung protein and transcript in mice and rats, respectively, following chronic alcohol ingestion or a caloric control diet. Liquid chromatography-mass spectrometry identified several mitochondrial-related proteins in which the expression was upregulated following long-term alcohol ingestion in mice. Consistent with these observations, rat gene chip microarray analysis of alveolar cells obtained from animals maintained on a Lieber-DeCarli liquid alcohol diet confirmed significant changes in mitochondrial-related transcripts in the alcohol lung. Transmission electron microscopy revealed significant changes in the mitochondrial architecture in alcohol mice, particularly following lipopolysaccharide exposure. Chronic alcohol ingestion was also shown to worsen mitochondrial respiration, mitochondrial membrane polarization, and NAD(+)-to-NADH ratios in alveolar type 2 cells. In summary, our studies show causal connection between chronic alcohol ingestion and mitochondrial dysfunction, albeit the specific role of each of the mitochondrial-related proteins and transcripts identified in our study requires additional study.
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, Georgia;
authors.forename: Abdel A
authors.initials: AA
authors.lastname: Alli
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; and.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Brewer
authors.affiliation: Department of Biological Sciences, Clark Atlanta University, Atlanta, Georgia.
authors.forename: Darrice S
authors.initials: DS
authors.lastname: Montgomery
authors.affiliation: Department of Biological Sciences, Clark Atlanta University, Atlanta, Georgia.
authors.forename: Marcus S
authors.initials: MS
authors.lastname: Ghant
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, Georgia; Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; and.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Eaton
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; and.
authors.forename: Lou Ann
authors.initials: LA
authors.lastname: Brown
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, Georgia; Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; and mhelms@emory.edu.
authors.forename: My N
authors.initials: MN
authors.lastname: Helms
mesh_terms: D000437:Alcoholism; D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000633:toxicity*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008933:Mitochondrial Swelling; D020411:Oligonucleotide Array Sequence Analysis; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D059467:Transcriptome / Q000187:drug effects
chemical_list: D002492:Central Nervous System Depressants; D008070:Lipopolysaccharides; D020543:Proteome; D000431:Ethanol
keywords: ENaC; chronic alcohol ingestion; gene chip array; mass spectrometry; mitochondrial stress