TY - JOUR
T1 - Assessment of structural features of the Pseudomonas siderophore pyochelin required for its ability to promote oxidant-mediated endothelial cell injury
AU - Britigan, Bradley E.
AU - DeWitte, Jon J.
AU - Rasmussen, George T.
AU - Britigan, Bradley E.
AU - Cox, Charles D.
AU - Britigan, Bradley E.
PY - 2001/9/15
Y1 - 2001/9/15
N2 - 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.
AB - 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.
KW - Endothelial cell
KW - Free radical
KW - Hydrogen peroxide
KW - Hydrophobicity
KW - Hydroxyl radical
KW - Iron
KW - Lung
KW - Pseudomonas aeruginosa
KW - Spin trapping
UR - http://www.scopus.com/inward/record.url?scp=0035883889&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035883889&partnerID=8YFLogxK
U2 - 10.1006/abbi.2001.2517
DO - 10.1006/abbi.2001.2517
M3 - Article
C2 - 11556810
AN - SCOPUS:0035883889
SN - 0003-9861
VL - 393
SP - 236
EP - 244
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 2
ER -