Subcellular localization of Pseudomonas pyocyanin cytotoxicity in human lung epithelial cells

Yunxia Q. O'Malley, Maher Y. Abdalla, Michael L. McCormick, Krzysztof J. Reszka, Gerene M. Denning, Bradley E. Britigan
2003 American Journal of Physiology - Lung cellular and Molecular Physiology  
The Pseudomonas aeruginosa secretory product pyocyanin damages lung epithelium, likely due to redox cycling of pyocyanin and resultant superoxide and H2O2 generation. Subcellular site(s) of pyocyanin redox cycling and toxicity have not been well studied. Therefore, pyocyanin's effects on subcellular parameters in the A549 human type II alveolar epithelial cell line were examined. Confocal and electron microscopy studies suggested mitochondrial redox cycling of pyocyanin and extracellular H 2O2
more » ... elease, respectively. Pyocyanin decreased mitochondrial and cytoplasmic aconitase activity, ATP levels, cellular reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, and mitochondrial membrane potential. These effects were transient at low pyocyanin concentrations and were linked to apparent cell-mediated metabolism of pyocyanin. Overexpression of MnSOD, but not CuZnSOD or catalase, protected cellular aconitase, but not ATP, from pyocyaninmediated depletion. This suggests that loss of aconitase activity is not responsible for ATP depletion. How pyocyanin leads to ATP depletion, the mechanism of cellular metabolism of pyocyanin, and the impact of mitochondrial pyocyanin redox cycling on other cellular events are important areas for future study. mitochondria; superoxide; hydrogen peroxide; aconitase PSEUDOMONAS AERUGINOSA CAUSES acute severe necrotizing pneumonia with high mortality (13, 34) as well as chronic lung infections in patients with cystic fibrosis (CF) or chronic bronchiectasis (12, 13, 34, 44) . Chronic lung injury is currently the primary cause of death in CF and has been linked to coexistent P. aeruginosa infection (12, 13). The pathogenic mechanism(s) involved in P. aeruginosa-mediated tissue damage in the lung remain uncertain (12, 13, 34, 44) .
doi:10.1152/ajplung.00316.2002 pmid:12414438 fatcat:ajjgem3bibamjpm57qmfx5nt5y