Photo-degradation of Porphyrin bounded hIAPP (1-37) Fibrils
Amyloid deposits in pancreatic islets of type 2 diabetes mellitus (T2DM) is mainly comprised of human islet amyloid polypeptide (hIAPP), which is believed to be generated as a paracrine hormone along with insulin secretion. Misfolded hIAPP fibrillation aggregated in islet beta cells is associated with T2DM. To reduce the risk of T2DM, amyloid aggregates degradation for removing insoluble amyloid deposits is proved to be a preventive strategy against T2DM. However, the development of the effective approaches and degradation mechanisms remain further addressed. Herein, we found tetrasodium-meso-tetra (4-sulfonatophenyl) porphyrin binding to hIAPP37 aggregates by the electrostatic interaction could enhance the degradability of hIAPP37 fibrils under photo-irradiation. The morphology change of hIAPP fibrils could be easily revealed due to the effect of photo-excited porphyrin by destabilizing β-sheet secondary structure under photo-irradiation without any additives in neutral condition. We validated that Photo-excited porphyrin induced degradation of amyloid fibrils may be attributed to reactive oxygen species, such as singlet oxygen, superoxide radicals and hydroxyl radicals, etc. Moreover, the degraded products of hIAPP37 fibrils shows low cytotoxicity to INS cells. This work could be beneficial for the molecular design of novel photo-degradation agents of amyloid fibrils and also expand the biomedical application of porphyrin from the photosensitization.