Assessment of structural features of the Pseudomonas siderophore pyochelin required for its ability to promote oxidant-mediated endothelial cell injury

Bradley E. Britigan, Jon J. DeWitte, George T. Rasmussen, Bradley E. Britigan, Charles D. Cox, Bradley E. Britigan

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

We previously showed that iron chelated to the Pseudomonas aeruginosa siderophore pyochelin enhances oxidant-mediated injury to pulmonary artery endothelial cells by catalyzing hydroxyl radical (HO) formation. Therefore, we examined pyochelin structural/chemical features that may be important in this process. Five pyochelin analogues were examined for (i) capacity to accentuate oxidant-mediated endothelial cell injury, (ii) HO catalytic ability, (iii) iron transfer to endothelial cells, and (iv) hydrophobicity. All compounds catalyzed similar HO. Production, but only the hydrophobic ones containing a thiazolidine ring enhanced cell injury. Transfer of iron to endothelial cells did not correlate with cytotoxicity. Finally, binding of Fe3+ by pyochelin led to Fe2+ formation, perhaps explaining how Fe3+-pyochelin augments H2O2-mediated cell injury via HO formation. The ability to bind iron in a catalytic form and the molecule’s thiazolidine ring, which increases its hydrophobicity, are key to pyochelin’s cytotoxicity. Reduction of Fe3+ to Fe2+ may also be important.

Original languageEnglish (US)
Pages (from-to)236-244
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume393
Issue number2
DOIs
StatePublished - Sep 15 2001
Externally publishedYes

Keywords

  • Endothelial cell
  • Free radical
  • Hydrogen peroxide
  • Hydrophobicity
  • Hydroxyl radical
  • Iron
  • Lung
  • Pseudomonas aeruginosa
  • Spin trapping

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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