title: Identification of proteins susceptible to thiol oxidation in endothelial cells exposed to hypochlorous acid and N-chloramines.
abstract: Hypochlorous acid (HOCl) is a potent oxidant produced by the enzyme myeloperoxidase, which is released by neutrophils under inflammatory conditions. Although important in the immune system, HOCl can also damage host tissue, which contributes to the development of disease. HOCl reacts readily with free amino groups to form N-chloramines, which also cause damage in vivo, owing to the extracellular release of myeloperoxidase and production of HOCl. HOCl and N-chloramines react readily with cellular thiols, which causes dysfunction via enzyme inactivation and modulation of redox signaling processes. In this study, the ability of HOCl and model N-chloramines produced on histamine and ammonia at inflammatory sites, to oxidize specific thiol-containing proteins in human coronary artery endothelial cells was investigated. Using a proteomics approach with the thiol-specific probe, 5-iodoacetamidofluorescein, we show that several proteins including peptidylprolyl isomerase A (cyclophilin A), protein disulfide isomerase, glyceraldehyde-3-phosphate dehydrogenase and galectin-1 are particularly sensitive to oxidation by HOCl and N-chloramines formed at inflammatory sites. This will contribute to cellular dysfunction and may play a role in inflammatory disease pathogenesis.
authors: Inflammation Group, The Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW 2042, Australia.
authors: Fiona A
authors: FA
authors: Summers
authors: Anna
authors: A
authors: Forsman Quigley
authors: Clare L
authors: CL
authors: Hawkins
mesh_terms: D002700:Chloramines / Q000633:toxicity*; D021984:Cyclophilin A / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005452:Fluoresceins / Q000737:chemistry; D037483:Galectin 1 / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D006997:Hypochlorous Acid / Q000633:toxicity*; D015335:Molecular Probes / Q000737:chemistry; D016877:Oxidants / Q000633:toxicity*; D010084:Oxidation-Reduction; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics; D013438:Sulfhydryl Compounds / Q000378:metabolism*
chemical_list: D002700:Chloramines; D005452:Fluoresceins; D037483:Galectin 1; D015335:Molecular Probes; D016877:Oxidants; D011506:Proteins; D013438:Sulfhydryl Compounds; C015296:5-iodoacetamidofluorescein; D006997:Hypochlorous Acid; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D021984:Cyclophilin A; D019704:Protein Disulfide-Isomerases