title: Amyloid aggregation of lysozyme: the synergy study of red wine polyphenols.
abstract: The amyloidoses are diseases associated with nonnative folding of proteins and characterized by the presence of protein amyloid aggregates. The ability of quercetin, resveratrol, caffeic acid, and their equimolar mixtures to affect amyloid aggregation of hen egg white lysozyme in vitro was detected by Thioflavin T fluorescence assay. The anti-amyloid activities of tested polyphenols were evaluated by the median depolymerization concentrations DC50 and median inhibition concentrations IC50 . Single substances are more efficient (by at least one order) in the depolymerization of amyloid aggregates assay than in the inhibition of the amyloid formation with IC50 in 10(-4) to 10(-5) M range. Analyzed mixture samples showed synergic or antagonistic effects in both assays. DC50 values ranged from 10(-5) to 10(-8) M and IC50 from 10(-5) to 10(-9) M, respectively. We observed that certain mixtures of studied polyphenols can synergistically inhibit production of amyloids aggregates and are also effective in depolymerization of the aggregates. Synergic or antagonistic effects of studied mixtures were correlated with protein-small ligand docking studies and AFM results. Differences in these activities could be explained by binding of each polyphenol to a different amino acid sequence within the protein. Our results indicate that synergic/antagonistic anti-amyloid effects of studied mixtures depend on the selective binding of polyphenols to the known amyloidogenic sequences in the lysozyme chain. Our findings of the effective reduction of amyloid aggregation of lysozyme by polyphenol mixtures in vitro are of the utter physiological relevance considering the bioavailability and low toxicity of tested phenols.
authors.affiliation: Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Košice, Slovakia.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Gazova
authors.forename: Katarina
authors.initials: K
authors.lastname: Siposova
authors.forename: Elena
authors.initials: E
authors.lastname: Kurin
authors.forename: Pavel
authors.initials: P
authors.lastname: Mučaji
authors.forename: Milan
authors.initials: M
authors.lastname: Nagy
mesh_terms: D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002109:Caffeic Acids / Q000378:metabolism*; D002645:Chickens; D008958:Models, Molecular; D009113:Muramidase / Q000378:metabolism*; D059808:Polyphenols / Q000378:metabolism; D011794:Quercetin / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000378:metabolism*; D014920:Wine / Q000032:analysis
chemical_list: D000682:Amyloid; D000975:Antioxidants; D002109:Caffeic Acids; D059808:Polyphenols; D013267:Stilbenes; D011794:Quercetin; C421864:hen egg lysozyme; D009113:Muramidase; D000077185:Resveratrol; C040048:caffeic acid