Sulfated polysaccharide ascophyllan prevents amyloid fibril formation of human insulin and inhibits amyloid-induced hemolysis and cytotoxicity in PC12 cells
Sulfated polysaccharide ascophyllan prevents amyloid fibril formation of human insulin and inhibits amyloid-induced hemolysis and cytotoxicity in PC12 cells
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DOI：
10.1093/bbb/zbab163
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发表时间：
2021-09-14
影响因子：
1.6
通讯作者：
Oda, Tatsuya
中科院分区：
文献类型：
--
作者：
Liang, Yan;Ueno, Mikinori;Oda, Tatsuya
我们发现，Ascophyllan显着抑制人胰岛素的原纤化，是最有效的硫酸多糖测试。凝胶过滤分析表明，Ascophyllan能够通过弱相互作用与胰岛素形成复合物。在原纤化条件下，胰岛素从天然α-螺旋到β-折叠主要结构的二级结构转变在Ascophyllan存在下受到抑制。有趣的是，Ascophyllan减弱胰岛素原纤维诱导的人红细胞溶血。此外，Ascophyllan减弱胰岛素淀粉样蛋白诱导的大鼠嗜铬细胞瘤PC 12细胞的细胞毒性，并降低细胞内活性氧水平。这是第一个报告表明，硫酸多糖，Ascophyllan，可以抑制胰岛素淀粉样纤维的形成和抑制纤维诱导的有害生物活性。
We found that ascophyllan significantly inhibited the fibrillation of human insulin and was the most effective among the sulfated polysaccharides tested. Gel-filtration analysis suggested that ascophyllan was capable of forming a complex with insulin through a weak interaction. Secondary structure transition from native alpha-helix to beta-sheet predominant structure of insulin under the fibrillation conditions was suppressed in the presence of ascophyllan. Interestingly, ascophyllan attenuated insulin fibril-induced hemolysis of human erythrocytes. Moreover, ascophyllan attenuated insulin amyloid-induced cytotoxicity on rat pheochromocytoma PC12 cells and reduced the level of intracellular reactive oxygen species. This is the first report indicating that a sulfated polysaccharide, ascophyllan, can suppress the insulin amyloid fibril formation and inhibit the fibril-induced detrimental bioactivities.