Evidence of the different effect of mercury and cadmium on the hIAPP aggregation process

Abstract

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 Hg2+ and Cd2+ 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. Hg2+ and Cd2+ each seem to modulate the peptide's ability to aggregate in a different way, suggesting a different mechanism of hIAPP toxicity.