聚乙二醇-聚醚嵌段共聚物对人胰岛淀粉样多肽寡聚化和纤维化的双重影响。
Dual effect of PEG-PE micelle over the oligomerization and fibrillation of human islet amyloid polypeptide.
机构信息
CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, P. R. China.
Radiation Chemistry Laboratory, Department of Chemistry, University of Agriculture, Faisalabad, 38000, Pakistan.
出版信息
Sci Rep. 2018 Mar 13;8(1):4463. doi: 10.1038/s41598-018-22820-w.
The oligomerization and fibrillation of human islet amyloid polypeptide (hIAPP) play a central role in the pathogenesis of type 2 diabetes. Strategies for remodelling the formation of hIAPP oligomers and fibrils have promising application potential in type 2 diabetes therapy. Herein, we demonstrated that PEG-PE micelle could inhibit hIAPP oligomerization and fibrillation through blocking the hydrophobic interaction and the conformational change from random coil to β-sheet structures of hIAPP. In addition, we also found that PEG-PE micelle could remodel the preformed hIAPP fibrils allowing the formation of short fibrils and co-aggregates. Taken together, PEG-PE micelle could rescue hIAPP-induced cytotoxicity by decreasing the content of hIAPP oligomers and fibrils that are related to the oxidative stress and cell membrane permeability. This study could be beneficial for the design and development of antiamyloidogenic agents.
人胰岛淀粉样多肽（hIAPP）的寡聚化和纤维形成在 2 型糖尿病的发病机制中起核心作用。重塑 hIAPP 寡聚体和纤维形成的策略在 2 型糖尿病治疗中具有广阔的应用潜力。本文中，我们证明了聚乙二醇-聚醚嵌段共聚物胶束可以通过阻断 hIAPP 的疏水性相互作用和从无规卷曲到 β-折叠结构的构象变化来抑制 hIAPP 的寡聚化和纤维形成。此外，我们还发现聚乙二醇-聚醚嵌段共聚物胶束可以重塑预形成的 hIAPP 纤维，从而形成短纤维和共聚集物。综上所述，聚乙二醇-聚醚嵌段共聚物胶束可以通过降低与氧化应激和细胞膜通透性相关的 hIAPP 寡聚体和纤维含量来挽救 hIAPP 诱导的细胞毒性。本研究有助于设计和开发抗淀粉样变剂。
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