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 journalArticle

13 Citations (Scopus)

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

Fingerprint

Siderophores
Endothelial cells
Pseudomonas
Oxidants
Endothelial Cells
Hydroxyl Radical
Wounds and Injuries
Iron
Thiazolidines
Cytotoxicity
Hydrophobicity
Hydrophobic and Hydrophilic Interactions
Pseudomonas aeruginosa
Pulmonary Artery
pyochelin
Molecules

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Assessment of structural features of the Pseudomonas siderophore pyochelin required for its ability to promote oxidant-mediated endothelial cell injury. / Britigan, Bradley E.; DeWitte, Jon J.; Rasmussen, George T.; Britigan, Bradley E.; Cox, Charles D.; Britigan, Bradley E.

In: Archives of Biochemistry and Biophysics, Vol. 393, No. 2, 15.09.2001, p. 236-244.

Research output: Contribution to journalArticle

Britigan, Bradley E. ; DeWitte, Jon J. ; Rasmussen, George T. ; Britigan, Bradley E. ; Cox, Charles D. ; Britigan, Bradley E. / Assessment of structural features of the Pseudomonas siderophore pyochelin required for its ability to promote oxidant-mediated endothelial cell injury. In: Archives of Biochemistry and Biophysics. 2001 ; Vol. 393, No. 2. pp. 236-244.
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