title: Carbon black and titanium dioxide nanoparticles elicit distinct apoptotic pathways in bronchial epithelial cells.
abstract: BACKGROUND
  Increasing environmental and occupational exposures to nanoparticles (NPs) warrant deeper insight into the toxicological mechanisms induced by these materials. The present study was designed to characterize the cell death induced by carbon black (CB) and titanium dioxide (TiO2) NPs in bronchial epithelial cells (16HBE14o- cell line and primary cells) and to investigate the implicated molecular pathways.
  
  
  RESULTS
  Detailed time course studies revealed that both CB (13 nm) and TiO2(15 nm) NP exposed cells exhibit typical morphological (decreased cell size, membrane blebbing, peripheral chromatin condensation, apoptotic body formation) and biochemical (caspase activation and DNA fragmentation) features of apoptotic cell death. A decrease in mitochondrial membrane potential, activation of Bax and release of cytochrome c from mitochondria were only observed in case of CB NPs whereas lipid peroxidation, lysosomal membrane destabilization and cathepsin B release were observed during the apoptotic process induced by TiO2 NPs. Furthermore, ROS production was observed after exposure to CB and TiO2 but hydrogen peroxide (H2O2) production was only involved in apoptosis induction by CB NPs.
  
  
  CONCLUSIONS
  Both CB and TiO2 NPs induce apoptotic cell death in bronchial epithelial cells. CB NPs induce apoptosis by a ROS dependent mitochondrial pathway whereas TiO2 NPs induce cell death through lysosomal membrane destabilization and lipid peroxidation. Although the final outcome is similar (apoptosis), the molecular pathways activated by NPs differ depending upon the chemical nature of the NPs.
authors.affiliation: Université Paris Diderot - Paris 7, Unit of Functional and Adaptive Biology (BFA) CNRS EAC 4413, Laboratory of Molecular and Cellular Responses to Xenobiotics, 75205 Paris, France.
authors.forename: Salik
authors.initials: S
authors.lastname: Hussain
authors.forename: Leen C J
authors.initials: LC
authors.lastname: Thomassen
authors.forename: Ioana
authors.initials: I
authors.lastname: Ferecatu
authors.forename: Marie-Caroline
authors.initials: MC
authors.lastname: Borot
authors.forename: Karine
authors.initials: K
authors.lastname: Andreau
authors.forename: Johan A
authors.initials: JA
authors.lastname: Martens
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Fleury
authors.forename: Armelle
authors.initials: A
authors.lastname: Baeza-Squiban
authors.forename: Francelyne
authors.initials: F
authors.lastname: Marano
authors.forename: Sonja
authors.initials: S
authors.lastname: Boland
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001980:Bronchi / Q000187:drug effects* / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053768:Metal Nanoparticles / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000473:pathology; D053260:Soot / Q000633:toxicity*; D014025:Titanium / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D002843:Chromatin; D017382:Reactive Oxygen Species; D053260:Soot; D051028:bcl-2-Associated X Protein; C009495:titanium dioxide; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D014025:Titanium; D020169:Caspases
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