Aluminium oxide nanoparticles induce structural changes in tau and cytotoxicity of the neuroblastoma cell line

Int J Biol Macromol. 2018 Dec;120(Pt A):1140-1148. doi: 10.1016/j.ijbiomac.2018.08.182. Epub 2018 Sep 1.

Abstract

The application of nanomaterials in the healthy system may induce some neurodegenerative diseases initiated by tau folding and neuronal cell death. Herein, aluminium oxide nanoparticles (Al2O3 NPs) were synthesized and characterized by XRD, TEM, DLS and zeta potential investigations. Afterwards, the interaction of Al2O3 NPs with tau protein was investigated by fluorescence and CD spectroscopic methods. The molecular docking and molecular dynamic were also run to explore the binding site and conformational changes of tau after interaction with Al2O3 cluster. Moreover, the MTT, LDH, caspase-9/-3 and flow cytometry assays were done to explore the Al2O3 NPs-induced cytotoxicity against SH-SY5Y cells. It was revealed that Al2O3 NPs bind to tau protein and form a static complex and fold the structure of tau toward a more packed structure. Molecular docking and molecular dynamic investigations revealed that NPs bind to the hydrophilic residues of the tau segments and promote some marginal structural folding of tau segment. The cellular assays displayed that Al2O3 NPs can elicit cell mortality through membrane leakage, caspase-9/-3 activations, and induction of both apoptosis and necrosis. This data may indicate that NPs can induce some adverse effects on the biological systems.

Keywords: Aluminium oxide; Interaction; Nanoparticle; Neuroblastoma cell; Tau protein.

MeSH terms

  • Aluminum Oxide / administration & dosage*
  • Aluminum Oxide / chemistry
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Metal Nanoparticles / administration & dosage*
  • Metal Nanoparticles / chemistry
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Neuroblastoma / chemistry
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / pathology
  • Protein Conformation / drug effects
  • tau Proteins / chemistry*
  • tau Proteins / drug effects

Substances

  • MAPT protein, human
  • tau Proteins
  • Aluminum Oxide