Bilirubin scavenges chloramines and inhibits myeloperoxidase-induced protein/lipid oxidation in physiologically relevant hyperbilirubinemic serum

Boon, A. C., Hawkins, C. L., Coombes, J. S., Wagner, K. H. and Bulmer, A. C. (2015) Bilirubin scavenges chloramines and inhibits myeloperoxidase-induced protein/lipid oxidation in physiologically relevant hyperbilirubinemic serum. Free Radical Biology and Medicine, 86 259-268. doi:10.1016/j.freeradbiomed.2015.05.031

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Author Boon, A. C.
Hawkins, C. L.
Coombes, J. S.
Wagner, K. H.
Bulmer, A. C.
Title Bilirubin scavenges chloramines and inhibits myeloperoxidase-induced protein/lipid oxidation in physiologically relevant hyperbilirubinemic serum
Journal name Free Radical Biology and Medicine   Check publisher's open access policy
ISSN 0891-5849
1873-4596
Publication date 2015-09
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.freeradbiomed.2015.05.031
Open Access Status File (Author Post-print)
Volume 86
Start page 259
End page 268
Total pages 10
Place of publication Philadelphia, PA United States
Publisher Elsevier
Language eng
Formatted abstract
Hypochlorous acid (HOCl), an oxidant produced by myeloperoxidase (MPO), induces protein and lipid oxidation, which is implicated in the pathogenesis of atherosclerosis. Individuals with mildly elevated bilirubin concentrations (i.e., Gilbert syndrome; GS) are protected from atherosclerosis, cardiovascular disease, and related mortality. We aimed to investigate whether exogenous/endogenous unconjugated bilirubin (UCB), at physiological concentrations, can protect proteins/lipids from oxidation induced by reagent and enzymatically generated HOCl. Serum/plasma samples supplemented with exogenous UCB (≤250 µM) were assessed for their susceptibility to HOCl and MPO/H2O2/Cl− oxidation, by measuring chloramine, protein carbonyl, and malondialdehyde (MDA) formation. Serum/plasma samples from hyperbilirubinemic Gunn rats and humans with GS were also exposed to MPO/H2O2/Cl− to: (1) validate in vitro data and (2) determine the relevance of endogenously elevated UCB in preventing protein and lipid oxidation. Exogenous UCB dose-dependently (P<0.05) inhibited HOCl and MPO/H2O2/Cl−-induced chloramine formation. Albumin-bound UCB efficiently and specifically (3.9–125 µM; P<0.05) scavenged taurine, glycine, and N-α-acetyllysine chloramines. These results were translated into Gunn rat and GS serum/plasma, which showed significantly (P<0.01) reduced chloramine formation after MPO-induced oxidation. Protein carbonyl and MDA formation was also reduced after MPO oxidation in plasma supplemented with UCB (P<0.05; 25 and 50 µM, respectively). Significant inhibition of protein and lipid oxidation was demonstrated within the physiological range of UCB, providing a hypothetical link to protection from atherosclerosis in hyperbilirubinemic individuals. These data demonstrate a novel and physiologically relevant mechanism whereby UCB could inhibit protein and lipid modification by quenching chloramines induced by MPO-induced HOCl.
Keyword Bile pigments
Heme oxygenase
Antioxidants
Protein oxidation
Myeloperoxidase
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Human Movement and Nutrition Sciences Publications
 
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Created: Wed, 19 Aug 2015, 09:55:32 EST by Sandrine Ducrot on behalf of School of Human Movement and Nutrition Sciences