title: Nanomaterial-induced cell death in pulmonary and hepatic cells following exposure to three different metallic materials: The role of autophagy and apoptosis.
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 TiO2NMs. Overall, the results show that high toxicity NMs can cause a dysfunction in the autophagy pathway which is associated with apoptotic cell death.
authors.affiliation: a Department of Public Health, Section of Environmental Health , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Ali
authors.initials: A
authors.lastname: Kermanizadeh
authors.affiliation: a Department of Public Health, Section of Environmental Health , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Jantzen
authors.affiliation: b Leeds Electron Microscopy and Spectroscopy (LEMAS) Centre , University of Leeds , Leeds , UK.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Ward
authors.affiliation: c Department of Cellular and Molecular Medicine , University of Copenhagen, Center for Healthy Aging , Copenhagen , Denmark.
authors.forename: Jon Ambæk
authors.initials: JA
authors.lastname: Durhuus
authors.affiliation: c Department of Cellular and Molecular Medicine , University of Copenhagen, Center for Healthy Aging , Copenhagen , Denmark.
authors.forename: Lene
authors.initials: L
authors.lastname: Juel Rasmussen
authors.affiliation: a Department of Public Health, Section of Environmental Health , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
authors.affiliation: a Department of Public Health, Section of Environmental Health , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
mesh_terms: D000072283:A549 Cells; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D018929:Cell Culture Techniques; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects / Q000473:pathology; D049329:Nanostructures / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D012834:Silver / Q000737:chemistry / Q000633:toxicity; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry / Q000633:toxicity; D015034:Zinc Oxide / Q000737:chemistry / Q000633:toxicity
chemical_list: C009495:titanium dioxide; D012834:Silver; D014025:Titanium; D015034:Zinc Oxide
keywords: Nanomaterials; apoptosis; autophagy; cell death; hepatic cells; pulmonary cells