Mitochondrial Peptide Humanin Protects Silver Nanoparticles-Induced Neurotoxicity in Human Neuroblastoma Cancer Cells (SH-SY5Y)

Int J Mol Sci. 2019 Sep 9;20(18):4439. doi: 10.3390/ijms20184439.

Abstract

The extensive usage of silver nanoparticles (AgNPs) as medical products such as antimicrobial and anticancer agents has raised concerns about their harmful effects on human beings. AgNPs can potentially induce oxidative stress and apoptosis in cells. However, humanin (HN) is a small secreted peptide that has cytoprotective and neuroprotective cellular effects. The aim of this study was to assess the harmful effects of AgNPs on human neuroblastoma SH-SY5Y cells and also to investigate the protective effect of HN from AgNPs-induced cell death, mitochondrial dysfunctions, DNA damage, and apoptosis. AgNPs were prepared with an average size of 18 nm diameter to study their interaction with SH-SY5Y cells. AgNPs caused a dose-dependent decrease of cell viability and proliferation, induced loss of plasma-membrane integrity, oxidative stress, loss of mitochondrial membrane potential (MMP), and loss of ATP content, amongst other effects. Pretreatment or co-treatment of HN with AgNPs protected cells from several of these AgNPs induced adverse effects. Thus, this study demonstrated for the first time that HN protected neuroblastoma cells against AgNPs-induced neurotoxicity. The mechanisms of the HN-mediated protective effect on neuroblastoma cells may provide further insights for the development of novel therapeutic agents against neurodegenerative diseases.

Keywords: DNA damage; apoptosis; cell death; humanin; mitochondrial dysfunctions; oxidative stress; silver nanoparticles.

MeSH terms

  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cell Membrane / pathology
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / pharmacology*
  • Membrane Potential, Mitochondrial / drug effects
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / toxicity*
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Mitochondrial Proteins / metabolism
  • Mitochondrial Proteins / pharmacology*
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Neurotoxicity Syndromes / drug therapy
  • Neurotoxicity Syndromes / metabolism
  • Neurotoxicity Syndromes / pathology
  • Oxidative Stress / drug effects
  • Silver / chemistry
  • Silver / toxicity*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Mitochondrial Proteins
  • humanin
  • Silver