The tea catechin epigallocatechin gallate inhibits NF- κB-mediated transcriptional activation by covalent modification.

The tea catechin epigallocatechin gallate inhibits NF-κB-mediated transcriptional activation by covalent modification. Arch Biochem Biophys. 2020 Oct 07;:108620 Authors: Lakshmi SP, Reddy AT, Kodidhela LD, Varadacharyulu NC Abstract Potential health benefits of consuming tea are thought to include anti-inflammatory actions of its constituent flavonoids including catechins, which are well-recognized antioxidants. We analyzed and discovered a novel mechanism by which epigallocatechin gallate (EGCG), the most abundant polyphenol in tea and a putative health-promoting constituent, inhibits activation of the nuclear transcription factor NF-κB, which mediates inflammatory responses to cytokines and other agents. We found that EGCG inhibits NF-κB-p65 transcriptional activity, by preventing NF-κB-p65 binding to κBs in normal human bronchial epithelial cells. We also analyzed the chemical mechanism by which EGCG binds directly to NF-κB-p65, and found that it involves covalent reaction via enones within EGCG ring structures, as the oxidizer diamide, which prevents 1, 4-addition reactions, blocked adduct-forming reaction of biotinylated EGCG with NF-κB-p65. Such blockade was inhibited by competing unlabeled EGCG. Furthermore, such covalent binding reflected irreversible reaction of EGCG with sulfhydryls of NF-κB-p65, as it was inhibited by glutathione but not reversible by it. We identified the reactive sulfhydryl moiety as that of cyst...
Source: Archives of Biochemistry and Biophysics - Category: Biochemistry Authors: Tags: Arch Biochem Biophys Source Type: research