Tau folding and cytotoxicity of neuroblastoma cells in the presence of manganese oxide nanoparticles: Biophysical, molecular dynamics, cellular, and molecular studies

Abstract

Manganese oxide nanoparticles (Mn₂O₃ NPs) have been widely used in the medical and biological applications. However, few studies have been undertaken to investigate the cytotoxicity of Mn₂O₃ NPs against nervous system. Herein, we studied the toxicity of Mn₂O₃ NPs against tau protein and neuroblastoma cells (SH-SY5Y) in vitro. Circular dichroism (CD) spectroscopy, fluorescence spectroscopy, molecular docking, and molecular dynamic studies were used to explore the conformational changes of protein. The cell-based experiments, such as viability, activation of caspases-3/9, apoptosis, and gene (Bax and Bcl-2) expression assays were performed in vitro. Spectroscopic methods and molecular dynamic studies revealed that Mn₂O₃ NPs can fold the structure of tau toward a more packed structure. The Mn₂O₃ NPs also decreased the cell viability in a dose-dependent manner. Indeed, caspase-3 and caspase-9 activation, Bax/Bcl-2 ratio elevation and apoptosis induction were observed after exposure of SH-SY5Y to Mn₂O₃ NPs. In conclusion, tau folding and cytotoxicity against SH-SY5Y cells may be involved in adverse effects induced by Mn₂O₃ NPs.

Keywords: Apoptosis; Cytotoxicity; Manganese oxide nanoparticles; Molecular dynamics; Neuroblastoma cells; Spectroscopy; Tau protein folding.