Polyphenol-induced dissociation of various amyloid fibrils results in a methionine-independent formation of ROS.
Fibrillization of amyloid polypeptides is accompanied by formation of reactive oxygen species (ROS), which, in turn, is assumed to further promote amyloid-related pathologies. Different polyphenols, all of which are established antioxidants, cause dissociation of amyloid fibrils. This study addresses the latter, poorly understood process. Specifically, we have investigated the dissociation of Abeta(42) fibrils by six different polyphenols, using electron microscopy and spectrofluorometric analysis. Simultanously, we have monitored the production of ROS using electron spin resonance (ESR) and the commercially available peroxide assay kit. Using the same methods we found that curcumin, one of the most potent destabilizing agents of Abeta(42), induced dissociation of fibrils of other amyloid polypeptides [Abeta(40), Abeta(42)Nle35, islet amyloid polypeptide and a fragment of alpha-synuclein]. When the solution contained traces of transition metal, all the dissociation reactions were accompanied by ROS formation, independent of the presence of a methionine residue. Kinetic studies show that the formation of ROS lags behind dissociation, indicating that if casual relationship exists between these two processes, then ROS formation may be considered a consequence and not a cause of dissociation. These findings open new avenues in amyloid research that will be required to gain further understanding of our results and of their implications.
Shoval
Hila
H
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Weiner
Lev
L
Gazit
Ehud
E
Levy
Michal
M
Pinchuk
Ilya
I
Lichtenberg
Dov
D
D000682:Amyloid / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide; D007700:Kinetics; D008715:Methionine / Q000494:pharmacology*; D008954:Models, Biological; D010545:Peroxides / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D011485:Protein Binding / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors
D000682:Amyloid; D005419:Flavonoids; D058228:Islet Amyloid Polypeptide; D010545:Peroxides; D010636:Phenols; D059808:Polyphenols; D017382:Reactive Oxygen Species; D002392:Catechin; D008715:Methionine; C045651:epigallocatechin gallate; D003474:Curcumin