Zinc Chelator Inhibits Zinc-Induced Islet Amyloid Polypeptide Deposition and Apoptosis in INS-1 Cells.

In this study, we aimed to investigate whether chelating zinc could inhibit zinc-induced amyloid deposits and apoptosis of islet beta cell. N, N, N', N'-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) is a specific chelator of zinc, with membrane permeability. It could effectively reduce the concentration of intracellular zinc. So, we used TPEN to treat hIAPP-transfected INS-1 cells. By MTT assay, the concentration (1 μM) and incubation time (12 h) of TPEN without affecting cell viability were determined. The results showed that TPEN reduced zinc-induced IAPP deposition in the culture system. Furthermore, we analyzed the effect of zinc and TPEN on the apoptosis and insulin level. The results showed that TPEN could reverse zinc-induced INS-1 cell apoptosis and insulin secretion. And the anti-apoptosis effects of TPEN is related to extracellular regulated protein kinases (ERK)/c-jun N-terminal kinase (JNK) signaling pathway. The present data indicated that chelating zinc could inhibit zinc-induced amyloid deposition and beta cell apoptosis. Thus, maintaining zinc homeostasis in islet beta cell might become a useful strategy for DM therapy. PMID: 30027367 [PubMed - as supplied by publisher]
Source: Biological Trace Element Research - Category: Biology Authors: Tags: Biol Trace Elem Res Source Type: research