Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari "Aldo Moro", via E. Orabona 4, 70126 Bari, Italy.
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari "Aldo Moro", via E. Orabona 4, 70126 Bari, Italy.
Biophys Chem. 2022 Nov;290:106880. doi: 10.1016/j.bpc.2022.106880. Epub 2022 Aug 31.
hIAPP is a hormone consisting of 37 aminoacids that shows a strong tendency to self-assemble into β-sheet-rich aggregates, which evolve to form insoluble aggregates that seem to be associated with β-cell degeneration in Type 2 Diabetes Mellitus. Numerous factors, intrinsic and extrinsic to the peptide molecule, appear to influence the hIAPP aggregation process. Different metal ions are able to interact with the hIAPP molecule, modulating its secondary structure and subsequently the peptide's capacity to aggregate. In this study, the effect of Hg and Cd on the hIAPP aggregation process was evaluated using direct and indirect methods. The kinetics and morphology of amyloid aggregate formation were respectively evaluated with Thioflavin T assays and electron microscopy, while the ability of the peptide to incorporate into POPC PLMs and form ion channels was monitored by single-channel current measurements. Hg and Cd each seem to modulate the peptide's ability to aggregate in a different way, suggesting a different mechanism of hIAPP toxicity.
hIAPP 是一种由 37 个氨基酸组成的激素，它具有很强的自组装成富含β-折叠的聚集体的趋势，这些聚集体进一步演变成不溶性聚集体，似乎与 2 型糖尿病中的β细胞退化有关。许多内在和外在的肽分子因素似乎都影响着 hIAPP 的聚集过程。不同的金属离子能够与 hIAPP 分子相互作用，调节其二级结构，从而改变肽的聚集能力。在这项研究中，使用直接和间接方法评估了 Hg 和 Cd 对 hIAPP 聚集过程的影响。采用硫黄素 T 试验和电子显微镜分别评估了淀粉样纤维形成的动力学和形态，同时通过单通道电流测量监测肽进入 POPC PLM 并形成离子通道的能力。Hg 和 Cd 似乎以不同的方式调节肽的聚集能力，这表明 hIAPP 毒性的作用机制不同。
