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

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

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 H2O2 release, 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 pyocyanin-mediated 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.

Original languageEnglish (US)
Pages (from-to)L420-L430
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume284
Issue number2 28-2
DOIs
StatePublished - Feb 1 2003

Keywords

  • Aconitase
  • Hydrogen peroxide
  • Mitochondria
  • Superoxide

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Fingerprint Dive into the research topics of 'Subcellular localization of Pseudomonas pyocyanin cytotoxicity in human lung epithelial cells'. Together they form a unique fingerprint.

Cite this