Bilirubin attenuates radical-mediated damage to serum albumin.
Oxidative damage to biological macromolecules has been implicated in a number of diseases. Much interest has focused on how non-proteinaceous, low-molecular weight antioxidants prevent oxidative damage to lipids, while comparatively little is known about protein antioxidation. Here we show that bilirubin (BR), the end-product of heme catabolism, when bound to bovine serum albumin (BSA), is oxidised by hydroxyl (.OH), hydroperoxyl (HO2.), and superoxide anion (O2-.) radicals to so far mostly uncharacterised products. The initial oxidation rates of BSA-bound BR decreased in the order OH > HO2. > O2-.. BR protected its carrier protein from oxidative damage inflicted by .OH radicals. This protective action included a reduction in the .OH-mediated cleavage of BSA, conversion of Trp into kynurenine and formation of 'bityrosine-specific' fluorescence. BR also strongly inhibited .OH-mediated formation of protein carbonyls, whereas ascorbate and Trolox (a water-soluble analogue of vitamin E) were much less effective. These results support an antioxidant-protective function of BR and point towards significant differences in the efficacies of various antioxidants in the prevention of oxidative damage to lipids and proteins.
Neuzil
J
J
Biochemistry Group, Heart Research Institute, Sydney, NSW, Australia.
Stocker
R
R
D000975:Antioxidants; D001663:Bilirubin / Q000502:physiology*; D005609:Free Radicals; D005720:Gamma Rays; D010084:Oxidation-Reduction; D012710:Serum Albumin, Bovine / Q000737:chemistry* / Q000528:radiation effects
D000975:Antioxidants; D005609:Free Radicals; D012710:Serum Albumin, Bovine; D001663:Bilirubin