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不同金属离子对人胰岛淀粉样多肽纤维形成的影响研究

朱栩姗，张雪利*，朱 平*
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2022年 第41卷 第3期: 1000-6281（2022）03-265-07     下载地址：

不同金属离子对人胰岛淀粉样多肽纤维形成的影响研究

朱栩姗，张雪利*，朱  平*

（中国科学院生物物理研究所，中国科学院大学中丹学院，中国-丹麦科研教育中心，北京100101）

摘    要  人胰岛淀粉样多肽（human islet amyloid polypeptide, hIAPP1-37）的淀粉样变性与II 型糖尿病关系紧密，而生长条件对hIAPP1-37 的纤维化过程有很大影响。体液中的金属离子失衡会促进纤维形成、增强细胞毒性。本文通过负染色透射电子显微镜（TEM）观察，辅以圆二色光谱（CD）和硫磺素T（ThT）荧光检测，探究了钠、钾等一价金属离子和镁、钙等二价金属离子对hIAPP1-37 纤维形态及形成过程的影响，发现hIAPP1-37 纤维在不同浓度金属离子盐溶液中呈现出两种不同形态，并且相同盐离子浓度条件下镁、钙等二价金属离子对于hIAPP1-37 纤维的形成具有比钠、钾等一价金属离子更显著的促进效果。分析表明，不同价态的金属离子主要通过改变hIAPP1-37 的疏水相互作用而影响淀粉样纤维的形成。

关键词    人胰岛淀粉样多肽；透射电子显微镜；圆二色光谱；ThT荧光检测；疏水作用

中图分类号：Q336；Q71；R587.1；O636  文献标识码：Adoi:10.3969/j.issn.1000-6281.2022.03.007

 

Study on the influences of different metal ions on the formation of human islet amyloid polypeptide fibrils

ZHU Xu-shan，ZHANG Xue-li*，ZHU Ping*

(Institute of Biophysics, Chinese Academy of Sciences, Sino-Danish College, University of Chinese Academy of Sciences, Sino-Danish Centre for Education and Research, Beijing 100101, China )

                                                                                            

Abstract     The amyloidosis of human islet amyloid polypeptide (hIAPP1-37) is closely associated with type 2 diabetes mellitus (T2DM), while growth conditions play crucial roles in the fibrillation process of hIAPP1-37. Moreover, the metal ions dyshomeostasis in body fluids promotes the formation of fibrils and enhances the cytotoxicity. In this paper, the negative staining transmission electron microscopy (TEM) analysis, accompanied with the circular dichroism (CD) and the Thioflavin-T (ThT) fluorescence assays, was performed to explore the influences of diverse monovalent metal cations, such as sodium and potassium ions, as well as divalent metal cations, such as magnesium and calcium ions, on the morphology and the formation process of hIAPP1-37 fibrils. Two different morphologies of the hIAPP1-37 fibrils were observed in the metal ion salt solutions with various concentrations. In addition, the promotive effects of magnesium and calcium ions on the hIAPP1-37 fibrils’ formation were found better than that of sodium and potassium ionswith the same concentration. Our results indicated that the metal ions affect the formation of amyloid fibrils principally through impacting the hydrophobic interactions within the hIAPP1-37.

Keywords     human islet amyloid polypeptide; transmission electron microscopy; circular dichroism; Thioflavin-T fluorescence assay; hydrophobic interaction

 

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