Natural polyphenols convert proteins into histone-binding ligands.

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Antioxidants, like vitamin C, readily oxidize and can modify proteins.
• Oxidized vitamin C-modified proteins exhibit histone-binding capabilities.
• This suggests oxidized antioxidants may generally function as protein modifiers.

Purpose of the Study:

• To identify natural polyphenols that can act as histone ligands after protein modification.
• To characterize the mechanism of interaction between polyphenol-modified proteins and histones.
• To elucidate the chemoprotective role of these interactions in endothelial cells.

Main Methods:

• Screening of 25 plant-derived polyphenols for their ability to convert bovine serum albumin into histone ligands.
• Characterization of polyphenol-protein interactions and their binding to histone tail domains.
• Assessment of the effect of polyphenol-modified proteins on histone-mediated cytotoxicity in endothelial cells.

Main Results:

• Seven polyphenols, including epigallocatechin-3-O-gallate (EGCG), were identified as histone ligand precursors.
• Polyphenol modification creates protein-based histone-binding elements interacting with histone tails.
• These interactions form aggregates and protect endothelial cells from histone-induced cytotoxicity.

Conclusions:

• Dietary polyphenols, upon oxidation and binding to proteins, can function as histone ligands.
• Histones are key targets for polyphenol-modified proteins.
• This mechanism contributes to the chemoprotective effects of dietary polyphenols.