title: Oxidative Deamination of Serum Albumins by (-)-Epigallocatechin-3-O-Gallate: A Potential Mechanism for the Formation of Innate Antigens by Antioxidants.
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.
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Hatasa
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Chikazawa
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Furuhashi
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Nakashima
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.|PRESTO, Japan Science and Technology Agency, Saitama, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shibata
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Biological Chemistry, Division of Applied Life Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Japan.
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Akagawa
authors.affiliation: Graduate School of Science and Engineering, Tokyo Institute of Technology, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hamagami
authors.affiliation: Graduate School of Science and Engineering, Tokyo Institute of Technology, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Faculty of Agriculture, Kyushu University, Fukuoka, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tachibana
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Uchida
mesh_terms: D000818:Animals; D000941:Antigens / Q000096:biosynthesis*; D000975:Antioxidants / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism; D002853:Chromatography, Liquid; D057930:Click Chemistry; D003641:Deamination; D005260:Female; D007113:Immunity, Innate; D051379:Mice; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D012709:Serum Albumin / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000941:Antigens; D000975:Antioxidants; D012709:Serum Albumin; D002392:Catechin; C045651:epigallocatechin gallate