Rifampicin inhibits the toxicity of pre-aggregated amyloid peptides by binding to peptide fibrils and preventing amyloid-cell interaction
Rifampicin inhibits the toxicity of pre-aggregated amyloid peptides by binding to peptide fibrils and preventing amyloid-cell interaction
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DOI：
10.1042/bj3220859
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发表时间：
1997-03-15
影响因子：
4.1
通讯作者：
Endo, N
中科院分区：
文献类型：
--
作者：
Tomiyama, T;Kaneko, H;Endo, N
利福平及其类似物，对苯醌和氢醌，抑制预先形成的人胰岛淀粉样多肽，胰淀素，大鼠嗜铬细胞瘤PC 12细胞的聚集体的毒性，当预孵育的聚集肽之前，除了细胞培养物。免疫荧光显微镜显示，他们阻止胰淀素聚集体粘附到细胞表面，这种效果可能是由他们的结合肽纤维在预孵育过程中诱导。其它醌衍生物，即，对甲氧基苯酚、AA-861和艾地苯醌不能抑制胰淀素聚集体的毒性和细胞表面粘附。利福平类似物也抑制预聚集的淀粉样蛋白β 1-42肽的毒性，表明不同淀粉样蛋白肽的共同毒性机制及其对几种淀粉样变性的治疗潜力。
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 beta 1-42 peptides, suggesting a common toxic mechanism of different amyloid peptides and their therapeutic potential for several amyloidoses.