Inhibition of amyloid fibrillization of hen egg-white lysozymes by rifampicin and p-benzoquinone.
It has been reported that more than 20 different human proteins can fold abnormally, resulting in the formation of pathological deposits and several lethal degenerative diseases. Despite extensive investigations on amyloid fibril formation, the detailed molecular mechanism remained rather elusive. The current research, utilizing hen egg-white lysozymes as a model system, is aimed at exploring inhibitory activities of two potential molecules against lysozyme fibril formation. We first demonstrated that the formation of lysozyme amyloid fibrils at pH 2.0 was markedly enhanced by the presence of agitation in comparison with its quiescent counterpart. Next, via numerous spectroscopic techniques and transmission electron microscopy, our results revealed that the inhibition of lysozyme amyloid formation by either rifampicin or its analogue p-benzoquinone followed a concentration-dependent fashion. Furthermore, while both inhibitors were shown to acquire an anti-aggregating and a disaggregating activity, rifampicin, in comparison with p-benzoquinone, served as a more effective inhibitor against in vitro amyloid fibrillogenesis of lysozyme. It is our belief that the data reported in this work will not only reinforce the findings validated by others that rifampicin and p-benzoquinone serve as two promising preventive molecules against amyloid fibrillogenesis, but also shed light on a rational design of effective therapeutics for amyloidogenic diseases.
Lieu
Valerie H
VH
Department of Chemical Engineering National Taiwan University, Taipei 10617, Taiwan.
Wu
Josephine W
JW
Wang
Steven S-S
SS
Wu
Chia-Hung
CH
D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D016227:Benzoquinones / Q000494:pharmacology*; D002942:Circular Dichroism; D003224:Congo Red / Q000737:chemistry; D007700:Kinetics; D046529:Microscopy, Electron, Transmission; D009113:Muramidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000648:ultrastructure; D011487:Protein Conformation / Q000187:drug effects; D012293:Rifampin / Q000494:pharmacology*
D000682:Amyloid; D016227:Benzoquinones; C004532:quinone; D003224:Congo Red; C421864:hen egg lysozyme; D009113:Muramidase; D012293:Rifampin