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Sulfated polysaccharide ascophyllan prevents amyloid fibril formation of human insulin and inhibits amyloid-induced hemolysis and cytotoxicity in PC12 cells.
Bioscience, Biotechnology, and Biochemistry ( IF 1.6 ) Pub Date : 2021-10-21 , DOI: 10.1093/bbb/zbab163
Yan Liang 1 , Mikinori Ueno 1 , Shijiao Zha 2 , Takasi Okimura 3 , Zedong Jiang 4, 5, 6, 7 , Kenichi Yamaguchi 1 , Tomomitsu Hatakeyama 8, 9 , Tatsuya Oda 1
Affiliation  

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 α-helix to β-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.

中文翻译:

硫酸化多糖 ascophyllan 可防止人胰岛素的淀粉样蛋白原纤维形成,并抑制淀粉样蛋白诱导的 PC12 细胞溶血和细胞毒性。

我们发现,叶黄素显着抑制人胰岛素的纤颤,并且在所测试的硫酸化多糖中是最有效的。凝胶过滤分析表明,叶黄素能够通过弱相互作用与胰岛素形成复合物。在存在叶绿素的情况下,在纤颤条件下,胰岛素从天然α-螺旋向β-折叠主要结构的二级结构转变被抑制。有趣的是,叶黄素减弱了胰岛素原纤维诱导的人红细胞溶血。此外,叶黄素减弱了胰岛素淀粉样蛋白诱导的大鼠嗜铬细胞瘤 PC12 细胞的细胞毒性,并降低了细胞内活性氧的水平。这是第一份表明硫酸化多糖、叶黄素、
更新日期:2021-09-14
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