title: Bilberry anthocyanins neutralize the cytotoxicity of co-chaperonin GroES fibrillation intermediates.
abstract: The co-chaperonin GroES (Hsp10) works with chaperonin GroEL (Hsp60) to facilitate the folding reactions of various substrate proteins. Upon forming a specific disordered state in guanidine hydrochloride, GroES is able to self-assemble into amyloid fibrils similar to those observed in various neurodegenerative diseases. GroES therefore is a suitable model system to understand the mechanism of amyloid fibril formation. Here, we determined the cytotoxicity of intermediate GroES species formed during fibrillation. We found that neuronal cell death was provoked by soluble intermediate aggregates of GroES, rather than mature fibrils. The data suggest that amyloid fibril formation and its associated toxicity toward cell might be an inherent property of proteins irrespective of their correlation with specific diseases. Furthermore, with the presence of anthocyanins that are abundant in bilberry, we could inhibit both fibril formation and the toxicity of intermediates. Addition of bilberry anthocyanins dissolved the toxic intermediates and fibrils, and the toxicity of the intermediates was thus neutralized. Our results suggest that anthocyanins may display a general and potent inhibitory effect on the amyloid fibril formation of various conformational disease-causing proteins.
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, ‡Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University , Tottori 680-8552, Japan.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Iwasa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kameda
authors.forename: Naoya
authors.initials: N
authors.lastname: Fukui
authors.forename: Sakiho
authors.initials: S
authors.lastname: Yoshida
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Hongo
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Mizobata
authors.forename: Saori
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawata
mesh_terms: D000682:Amyloid / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D000978:Antiparkinson Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019587:Dietary Supplements / Q000032:analysis; D029968:Escherichia coli Proteins / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000648:ultrastructure; D005638:Fruit / Q000737:chemistry*; D006360:Heat-Shock Proteins / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000648:ultrastructure; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008970:Molecular Weight; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry; D017510:Protein Folding / Q000187:drug effects; D012995:Solubility; D029800:Vaccinium myrtillus / Q000737:chemistry*
chemical_list: D000682:Amyloid; D000872:Anthocyanins; D000978:Antiparkinson Agents; D029968:Escherichia coli Proteins; C028715:GroE protein, E coli; D006360:Heat-Shock Proteins; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D010936:Plant Extracts