Nanomaterial-induced cell death in pulmonary and hepatic cells following exposure to three different metallic materials: The role of autophagy and apoptosis

Ali Kermanizadeh, Kim Jantzen, Michael B. Ward, Jon Ambæk Durhuus, Lene Juel Rasmussen, Steffen Loft, Peter Møller

Research output: Contribution to journalArticle

16 Citations (Scopus)
11 Downloads (Pure)

Abstract

Autophagy is the catabolic process involving the sequestration of the cytoplasm within double-membrane vesicles, which fuse with lysosomes to form autolysosomes in which autophagic targets are degraded. Since most endocytic routes of nanomaterial uptake converge upon the lysosome and the possibility that autophagy induction by NMs may be an attempt by the cell to self-preserve following the external challenge, this study investigated the role of autophagy following exposure to a panel of widely used metal-based NMs with high toxicity (Ag and ZnO) or low toxicity (TiO2) in a pulmonary (A549) and hepatic (HepG2) cell line. The in vitro exposure to the Ag and ZnO NMs resulted in the induction of both apoptosis and autophagy pathways in both cell types. However, the progression of autophagy was blocked in the formation of the autolysosome, which coincided with morphologic changes in the actin cytoskeleton. This response was not observed following the exposure to low-toxicity TiO2 NMs. Overall, the results show that high toxicity NMs can cause a dysfunction in the autophagy pathway which is associated with apoptotic cell death.

Original languageEnglish
Pages (from-to)184-200
Number of pages17
JournalNanotoxicology
Volume11
Issue number2
Early online date24 Jan 2017
DOIs
Publication statusPublished - 7 Feb 2017

Keywords

  • A549 Cells
  • Apoptosis/drug effects
  • Autophagy/drug effects
  • Cell Culture Techniques
  • Hep G2 Cells
  • Humans
  • Liver/drug effects
  • Lung/drug effects
  • Lysosomes/drug effects
  • Nanostructures/chemistry
  • Particle Size
  • Silver/chemistry
  • Surface Properties
  • Titanium/chemistry
  • Zinc Oxide/chemistry

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