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硫酸多糖藻朊酸能阻止人胰岛素形成淀粉样纤维,并能抑制淀粉样蛋白诱导的 PC12 细胞溶血和细胞毒性。

Sulfated polysaccharide ascophyllan prevents amyloid fibril formation of human insulin and inhibits amyloid-induced hemolysis and cytotoxicity in PC12 cells.

机构信息

Graduate School of Fisheries Science and Environmental Studies, Nagasaki University, Bunkyo-machi, Nagasaki, Japan.

School of Earth and Environment, Anhui University of Science and Technology, Huainan, China.

出版信息

Biosci Biotechnol Biochem. 2021 Oct 21;85(11):2281-2291. doi: 10.1093/bbb/zbab163.

Abstract

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.

摘要

我们发现泡叶藻聚糖可显著抑制人胰岛素的聚集,且在测试的硫酸多糖中抑制效果最为显著。凝胶过滤分析表明,泡叶藻聚糖可通过弱相互作用与人胰岛素形成复合物。在存在泡叶藻聚糖的情况下,胰岛素在聚集条件下由天然的 α-螺旋向 β-折叠优势结构的二级结构转变受到抑制。有趣的是,泡叶藻聚糖可减轻胰岛素纤维诱导的人红细胞溶血。此外,泡叶藻聚糖可减轻胰岛素原纤维诱导的大鼠嗜铬细胞瘤 PC12 细胞毒性,并降低细胞内活性氧水平。这是首个表明硫酸多糖泡叶藻聚糖可抑制胰岛素原纤维形成并抑制纤维诱导的有害生物活性的报告。

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