Rifampicin inhibits the toxicity of pre-aggregated amyloid peptides by binding to peptide fibrils and preventing amyloid-cell interaction

• Published in: Biochemical journal Vol. 322 ( Pt 3); no. 3; pp. 859 - 865
• Main Authors: Tomiyama, T, Kaneko, H, Kataoka, K i, Asano, S, Endo, N
• Format: Journal Article
• Language: English
• Published: England 15.03.1997
• Subjects: Amyloid - antagonists & inhibitors; Amyloid - metabolism; Amyloid - ultrastructure; Animals; Humans; Leprostatic Agents - pharmacology; Microscopy, Fluorescence; PC12 Cells; Protein Binding - drug effects; Rats; Rifampin - pharmacology
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj3220859

Rifampicin and its analogues, p-benzoquinone and hydroquinone, inhibited the toxicity of preformed aggregates of human islet amyloid polypeptide, amylin, to rat pheochromocytoma PC12 cells, when preincubated with the aggregated peptide before addition to cell cultures. Immunofluorescence microscopy showed that they prevented the adhesion of amylin aggregates to the cell surface, and this effect was induced probably by their binding to peptide fibrils during preincubation. Other quinone derivatives, i.e., p-methoxyphenol, AA-861 and idebenone, failed to inhibit the toxicity and cell-surface adhesion of amylin aggregates. Rifampicin analogues also inhibited the toxicity of pre-aggregated amyloid beta1-42 peptides, suggesting a common toxic mechanism of different amyloid peptides and their therapeutic potential for several amyloidoses.