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.

Green tea polyphenolic antioxidants oxidize hydrogen sulfide to thiosulfate and polysulfides: A possible new mechanism underpinning their biological action

“…The effects of catechins in cells could also arise from factors in addition to oxidation of H 2 S to polysulfides. A number of studies have shown that EGCG, but not EC or EGC, uniquely inhibits proteins, including enzymes, by fitting into the active site pocket via hydrogen bonds and van der Waals forces [ 33 , 35 , 80 ]. Catechins also react with the sulfur or seleniun group of reduced thioredoxin (Trx) or thoiredoxin reductase (TrxR), respectively, thereby inhibiting the enzymes [ [72] , [73] , [74] ].…”

Therapeutic Role of Green Tea Polyphenols in Improving Fertility: A Review

“…The antioxidant properties of polyphenols comprise scavenging and destroying free radicals. Testicular tissue is predisposed to suffer from the action of free radicals and OS because of its high cell division rate, oxygen consumption rate, and low oxygen pressure, debilitated vessels, and high levels of unsaturated fatty acids [ 87 ]. In addition to its antioxidant properties, green tea may also decrease inflammation, reduce DNA fragmentation, and increase the motility and viability of semen [ 88 ].…”

Thermodynamic and computational analyses reveal the functional roles of the galloyl group of tea catechins in molecular recognition

“…For example, flavonoids, including catechins derivatives, interact with HSA [ 14 , 15 ] and are transported to various tissues, resulting in various biological activities. Although it has been already reported that catechins interact with HSA [ 15 , 16 ] and the interaction could increase the cross-reactivity of EGCg with natural IgM antibodies in mouse serum [ 17 ], the molecular-level details of how catechins are recognized by HSA remain unclear. Understanding structure–activity relationships requires an understanding of the thermodynamics of ligand–protein interactions, and the combination of isothermal titration calorimetry (ITC) and spectroscopic techniques has been used to investigate the interaction between HSA and (+)-catechin [ 18 ].…”