title: Pseudomonas pyocyanine alters calcium signaling in human airway epithelial cells.
abstract: Pseudomonas aeruginosa, an opportunistic human pathogen, causes both acute and chronic lung disease. P. aeruginosa exerts many of its pathophysiological effects by secreting virulence factors, including pyocyanine, a redox-active compound that increases intracellular oxidant stress. Because oxidant stress has been shown to affect cytosolic Ca2+ concentration ([Ca2+]c) in other cell types, we studied the effect of pyocyanine on [Ca2+]c in human airway epithelial cells (A549 and HBE). At lower concentrations, pyocyanine inhibits inositol 1,4,5-trisphosphate formation and [Ca2+]c increases in response to G protein-coupled receptor agonists. Conversely, at higher concentrations, pyocyanine itself increases [Ca2+]c. The pyocyanine-dependent [Ca2+]c increase appears to be oxidant dependent and to result from increased inositol trisphosphate and release of Ca2+ from intracellular stores. Ca2+ plays a central role in epithelial cell function, including regulation of ion transport, mucus secretion, and ciliary beat frequency. By disrupting Ca2+ homeostasis, pyocyanine could interfere with these critical functions and contribute to the pathophysiological effects observed in Pseudomonas-associated lung disease.
authors.affiliation: Department of Internal Medicine, Veterans Affairs Medical Center and The University of Iowa, Iowa City, Iowa, 52242, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Denning
authors.forename: M A
authors.initials: MA
authors.lastname: Railsback
authors.forename: G T
authors.initials: GT
authors.lastname: Rasmussen
authors.forename: C D
authors.initials: CD
authors.lastname: Cox
authors.forename: B E
authors.initials: BE
authors.lastname: Britigan
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D010084:Oxidation-Reduction; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism*; D011710:Pyocyanine / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction
chemical_list: D011956:Receptors, Cell Surface; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D011710:Pyocyanine; D019204:GTP-Binding Proteins; D002118:Calcium