Acetaldehyde-mediated cilia dysfunction in bovine bronchial epithelial cells.
Acetaldehyde, which is present in significant concentrations in cigarette smoke and is elevated during alcohol ingestion, has been demonstrated to impair mucociliary clearance of the lung. Acetaldehyde is also known to impair protein function through the formation of acetaldehyde-protein adducts. We hypothesized that acetaldehyde impairs bronchial epithelial cilia motion by inhibiting cilia dynein adenosinetriphosphatase (ATPase) activity through the formation of acetaldehyde adducts with cilia proteins. Acetaldehyde induced concentration- and time-dependent slowing of cilia beating and cilia-derived dynein ATPase activity in primary cultures and isolated axonemes of bovine airway epithelial cells. Cilia slowing and ATPase inhibitory effects were also observed with related aldehydes but not with ethanol. Acetaldehyde binding, assessed by gel electrophoresis using [14C] acetaldehyde, was demonstrated to occur with the dynein heavy chains and with tubulin and closely paralleled ATPase inhibition. We conclude that acetaldehyde directly impairs bronchial cilia function causing slowing of cilia beating, inhibits cilia dynein ATPase activity, and binds to cilia proteins critical for motion including dynein and tubulin. These data suggest that acetaldehyde-induced cilia dysfunction may be related to direct cilia ATPase inactivation and adduct formation with cilia dynein and tubulin. This may be an important mechanism by which airway host defenses are impaired in clinical settings where acetaldehyde exposure occurs, e.g., with cigarette smoking and alcohol ingestion.
Sisson
J H
JH
Department of Medicine, University of Nebraska Medical Center, Omaha 68105-1065.
Tuma
D J
DJ
Rennard
S I
SI
D000079:Acetaldehyde / Q000378:metabolism / Q000494:pharmacology*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001980:Bronchi / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects / Q000502:physiology*; D004398:Dyneins / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology; D007700:Kinetics; D011485:Protein Binding
D000447:Aldehydes; D000431:Ethanol; D000251:Adenosine Triphosphatases; D004398:Dyneins; D000079:Acetaldehyde