Title :

The polyphenol (-)-epigallocatechin-3-gallate prevents apoA-IIowa amyloidosis in vitro and protects human embryonic kidney 293 cells against amyloid cytotoxicity

Author(s) :

Nakajima, Hiroyuki [Auteur]
Nishitsuji, Kazuchika [Auteur]
Kawashima, Hiroyuki [Auteur]
Kuwabara, Kaori [Auteur]
Mikawa, Shiho [Auteur]
Uchimura, Kenji [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Akaji, Kenichi [Auteur]
Kashiwada, Yoshiki [Auteur]
Kobayashi, Norihiro [Auteur]
Saito, Hiroyuki [Auteur]
Sakashita, Naomi [Auteur]

Journal title :

Amyloid. The International Journal of Experimental and Clinical Investigation. The Official Journal of the International Society of Amyloidosis

Abbreviated title :

Amyloid

Volume number :

23

Pages :

17-25

Publication date :

2016

ISSN :

1744-2818

English keyword(s) :

Catechin
Reactive Oxygen Species
Protein Structure, Secondary
Cell Survival
Humans
EGCG
Protein Aggregation, Pathological
recombinant amyloidogenic proteins
HEK293 Cells
Apolipoprotein A-I
Amyloidosis
Amyloid
Drug Evaluation, Preclinical
oxidative stress

HAL domain(s) :

Chimie/Chimie théorique et/ou physique

English abstract : [en]

INTRODUCTION: Apolipoprotein A-I (apoA-I) amyloidosis is either a non-hereditary form with deposits of wild-type apoA-I proteins in atherosclerotic plaques or a hereditary form with progressive accumulation of mutant apoA-I ...
Show more >INTRODUCTION: Apolipoprotein A-I (apoA-I) amyloidosis is either a non-hereditary form with deposits of wild-type apoA-I proteins in atherosclerotic plaques or a hereditary form with progressive accumulation of mutant apoA-I proteins in different tissues. Several small polyphenolic molecules reportedly inhibited formation of fibrillar assemblies of some amyloidogenic proteins and their cytotoxicity, but small molecules that inhibit apoA-I fibril formation have never been reported. METHODS: Our methods included a thioflavin-T-binding assay, atomic force microscopy and dot blot and cell-based assays. RESULTS: We showed that (-)-epigallocatechin-3-gallate (EGCG), a tea-derived flavanol, inhibited in vitro fibril formation and disaggregated fibrils preformed by the N-terminal 1-83 fragments of wild-type (WT) apoA-I and the G26R point mutation of apoA-I (apoA-IIowa). We eliminated a common structure recognized by the anti-amyloid antibody OC by incubating apoA-IIowa with EGCG or treating apoA-IIowa fibrils with EGCG, which supported the above observation. In addition, EGCG rescued human embryonic kidney 293 cells from cytotoxicity and attenuated production of reactive oxygen species, which were induced by apoA-IIowa fibrils. CONCLUSIONS: Our results support the concept that EGCG inhibits amyloid fibril formation of various amyloidogenic proteins. Thus, EGCG may be a candidate for providing a structure to develop de novo inhibitors for amyloidosis treatment.Show less >

Language :

Anglais

Administrative institution(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Submission date :

2020-02-12T15:11:37Z