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论文类型：期刊论文

发表刊物：ACS Applied Materials & Interfaces

收录刊物：SCI

卷号：10

期号：37

页面范围：31069-31079

ISSN号：1944-8244

DOI码：10.1021/acsami.8b11078

发表时间：2018-08-27

影响因子：8.456

摘要：Misfolding and aggregation of human islet amyloid polypeptide (hIAPP) into fibrils are important contributions to the pathology of type 2 diabetes. Developing effective inhibitors of protein aggregation and fibrillation has been considered a promising therapeutic approach to preventing and treating type 2 diabetes. Herein, we report that Shiitake-derived polysaccharide lentinan manipulates in vitro hIAPP fibrillation and modulates IAPP-induced cytotoxicity in a conformation-dependent manner. In its triple-helical conformation, lentinan effectively inhibits hIAPP fibrillation, either in bulk solution or in the presence of lipid membrane, suppresses reactive oxygen species (ROS) generation, and attenuates hIAPP-induced cell toxicity. In contrast, lentinan accelerates hIAPP aggregation when it exists in a random-coil conformation and shows no suppression on hIAPP-mediated ROS production. Further investigation shows that the interaction between triple-helical lentinan and monomeric hIAPP is more favorable than the intermolecular binding of hIAPP, which redirects hIAPP aggregates to discrete nontoxic nanocomposites. To the best of our knowledge, this is the first time to report a conformation-dependent inhibition of hIAPP aggregation, which will provide new insights for our understanding of the manipulation mechanisms on hIAPP by natural polysaccharides and open a new avenue for designing and screening potential amyloid inhibitors against type 2 diabetes

发布期刊链接：https://pubs.acs.org/doi/10.1021/acsami.8b11078