title: Identification of plasma proteins that are susceptible to thiol oxidation by hypochlorous acid and N-chloramines.
abstract: Hypochlorous acid (HOCl), the major strong oxidant produced by myeloperoxidase, reacts readily with free amino groups to form N-chloramines. Although HOCl and N-chloramines play an important role in the human immune system by killing bacteria and invading pathogens, they have also been shown to cause damage to tissues, which is believed to contribute to a number of diseases. It has been shown previously that N-chloramines react more readily with protein thiols than with other targets in plasma, but the nature of the plasma thiol-containing proteins oxidized is unknown. In this study, the ability of N-chloramines to selectively oxidize thiol-containing plasma proteins was determined using the thiol-specific probe, 5-iodoacetamidofluorescein, combined with two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Experiments were performed with N-chloramines formed on Nalpha-acetyl-lysine, Nalpha-acetyl-histidine (HisCA), glycine, taurine, and ammonia. With the exception of HisCA, the N-chloramines were more efficient than HOCl at oxidizing plasma thiols. The thiol-containing plasma proteins alpha1-antitrypsin and transthyretin were found to be oxidized in addition to albumin, with this treatment resulting in the inactivation of alpha1-antitrypsin. A similar selectivity of reaction and extent of thiol oxidation were also observed with myeloperoxidase in the presence of hydrogen peroxide and chloride ions.
authors.affiliation: The Heart Research Institute, Camperdown, Sydney, NSW 2050, Australia.
authors.forename: Fiona A
authors.initials: FA
authors.lastname: Summers
authors.forename: Philip E
authors.initials: PE
authors.lastname: Morgan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davies
authors.forename: Clare L
authors.initials: CL
authors.lastname: Hawkins
mesh_terms: D001798:Blood Proteins / Q000737:chemistry*; D002700:Chloramines / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D006997:Hypochlorous Acid / Q000737:chemistry*; D008297:Male; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000737:chemistry; D012016:Reference Values; D013438:Sulfhydryl Compounds / Q000097:blood* / Q000737:chemistry*; D000515:alpha 1-Antitrypsin / Q000097:blood
chemical_list: D001798:Blood Proteins; D002700:Chloramines; D016877:Oxidants; D013438:Sulfhydryl Compounds; D000515:alpha 1-Antitrypsin; D006997:Hypochlorous Acid; D009195:Peroxidase