Abstract
(-)-Epigallocatechin-3-O-gallate (EGCG), the most abundant polyphenol in green tea, mediates the oxidative modification of proteins, generating protein carbonyls. However, the underlying molecular mechanism remains unclear. Here we analyzed the EGCG-derived intermediates generated upon incubation with the human serum albumin (HSA) and established that EGCG selectively oxidized the lysine residues via its oxidative deamination activity. In addition, we characterized the EGCG-oxidized proteins and discovered that the EGCG could be an endogenous source of the electrically-transformed proteins that could be recognized by the natural antibodies. When HSA was incubated with EGCG in the phosphate-buffered saline (pH 7.4) at 37°C, the protein carbonylation was associated with the formation of EGCG-derived products, such as the protein-bound EGCG, oxidized EGCG, and aminated EGCG. The aminated EGCG was also detected in the sera from the mice treated with EGCG in vivo. EGCG selectively oxidized lysine residues at the EGCG-binding domains in HSA to generate an oxidatively deaminated product, aminoadipic semialdehyde. In addition, EGCG treatment results in the increased negative charge of the protein due to the oxidative deamination of the lysine residues. More strikingly, the formation of protein carbonyls by EGCG markedly increased its cross-reactivity with the natural IgM antibodies. These findings suggest that many of the beneficial effects of EGCG may be partly attributed to its oxidative deamination activity, generating the oxidized proteins as a target of natural antibodies.
Highlights
Oxidative modification of proteins and subsequent accumulation of oxidized proteins, an indication of oxidative tissue damage, has been reported in diseased tissues from age-related pathologies, such as atherosclerosis, neurodegenerative disorders, and cataract [1]
There is ample evidence to support the notion that the most important mechanism of oxidative damage to proteins is metal-catalyzed oxidation. This process includes the generation of H2O2 and reduction of Fe3+ or Cu2+ by a suitable electron donor; Fe2+ and Cu+ ions bind to specific metal binding sites on proteins and react with H2O2 to generate reactive oxygen species, such as the hydroxyl radical
To establish the oxidative deamination activity of EGCG, we sought to detect the EGCGderived products generated upon incubation of human serum albumin (HSA) with EGCG
Summary
Oxidative modification of proteins and subsequent accumulation of oxidized proteins, an indication of oxidative tissue damage, has been reported in diseased tissues from age-related pathologies, such as atherosclerosis, neurodegenerative disorders, and cataract [1]. There is ample evidence to support the notion that the most important mechanism of oxidative damage to proteins is metal-catalyzed oxidation This process includes the generation of H2O2 and reduction of Fe3+ or Cu2+ by a suitable electron donor; Fe2+ and Cu+ ions bind to specific metal binding sites on proteins and react with H2O2 to generate reactive oxygen species, such as the hydroxyl radical. They can lead to oxidation of amino acid residue side chains, formation of protein-protein cross-linkages, and oxidation of the protein backbone resulting in protein fragmentation. Given the large number of studies suggesting the involvement of oxidative protein modification in diseases, the significance of the findings in this report may be far-reaching
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
